J Hepatol. 2010 Nov 11. [Epub ahead of print]
Manns MP, Bourlière M, Benhamou Y, Pol S, Bonacini M, Trepo C, Wright D, Berg T, Calleja JL, White PW, Stern JO, Steinmann G, Yong CL, Kukolj G, Scherer J, Boecher WO.
Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Center for Internal Medicine, Hannover, Germany.
Abstract
BACKGROUND AND AIMS: BI201335 is a highly specific and potent HCV protease inhibitor. This multiple rising dose trial evaluated antiviral activity and safety in chronic HCV genotype-1 patients.
METHODS: 34 treatment-naïve patients were randomized to monotherapy with placebo or BI201335 at 20-240 mg once-daily for 14 days, followed by combination with pegylated interferon alfa/ribavirin (PegIFN/RBV) through Day 28. Nineteen treatment-experienced patients received 48-240 mg BI201335 once-daily with PegIFN/RBV for 28 days. HCV-RNA was measured with Roche COBAS TaqMan.
RESULTS: In treatment naïve patients, median maximal viral load (VL) reductions during 14 day monotherapy were -3.0, -3.6, -3.7 and -4.2 log(10) for the 20, 48, 120, and 240 mg groups. VL breakthroughs (⩾1 log(10) from nadir) were seen in most patients on monotherapy and were caused by NS3/4A variants (R155K, D168V) conferring in vitro resistance to BI201335. Adding PegIFN/RBV at Days 15 to 28 led to continuous viral load reductions in most patients. In treatment-experienced patients, treatment with BI201335 and PegIFN/RBV achieved VL <25 IU/ml at Day 28 in 3/6, 4/7 and 5/6 patients in the 48, 120 and 240 mg dose groups. VL breakthroughs were observed during triple combination in only 3/19 patients. BI201335 was generally well tolerated. Mild rash or photosensitivity was detected in 4 patients. Mild unconjugated hyperbilirubinemia was the only dose-dependent laboratory abnormality of BI201335. BI201335 elimination half-life supports once-daily dosing.
CONCLUSIONS: BI201335 combined with PegIFN/RBV was well tolerated and induced strong antiviral responses. These results support further development of BI201335 in HCV genotype-1 patients.
Copyright © 2010. Published by Elsevier B.V.
PMID: 21145839 [PubMed - as supplied by publisher]
Source
December 19, 2010
Treatment of Chronic Hepatitis C Patients with the NS3/4A Protease Inhibitor Danoprevir (ITMN-191/RG7227) Leads to Robust Reductions in Viral RNA: A Phase 1b Multiple Ascending Dose Study
J Hepatol. 2010 Dec 8. [Epub ahead of print]
Forestier N, Larrey D, Guyader D, Marcellin P, Rouzier R, Patat A, Smith P, Bradford W, Porter S, Blatt L, Seiwert SD, Zeuzem S.
J.W. Goethe Universität, Frankfurt, Germany.
Abstract
Danoprevir is a potent and selective inhibitor of the hepatitis C virus (HCV) NS3/4A serine protease. The present study assessed the safety, pharmacokinetics and antiviral activity of danoprevir in a randomized, placebo-controlled, 14-day multiple ascending dose study in patients with chronic HCV genotype 1 infection. Four cohorts of treatment-naïve (TN) patients (100 mg q12h, 100 mg q8h, 200 mg q12h, 200 mg q8h) and one cohort of non-responders (NR) to prior pegylated interferon alfa-ribavirin treatment (300 mg q12h) were investigated. RESULTS: Danoprevir was safe and well tolerated; adverse events were generally mild, transient and without association to treatment group or dose level. Danoprevir displayed a slightly more than proportional increase in exposure with increasing daily dose and was rapidly eliminated from the plasma compartment. Maximal decreases in HCV RNA were -3.9 log(10) IU/mL and -3.2 log(10) IU/mL in TN receiving 200 mg q8h and 200 mg q12h, respectively. End of treatment viral decline in these two cohorts was within 0.1 log(10) IU/mL of viral load nadir. HCV RNA reduction in NR was more modest than that observed in upper dose TN cohorts. The overall incidence of viral rebound was low (10/37) and was associated with R155K substitution in NS3 regardless of HCV subtype. CONCLUSION: Danoprevir was safe and well tolerated when administered for 14 days in patients with chronic HCV genotype 1 infection. Treatment resulted in sustained, multi-log(10) IU/mL reductions in HCV RNA in upper dose cohorts. These results support further clinical evaluation of danoprevir in patients with chronic HCV.
Copyright © 2010. Published by Elsevier B.V.
PMID: 21145848 [PubMed - as supplied by publisher]
Source
Forestier N, Larrey D, Guyader D, Marcellin P, Rouzier R, Patat A, Smith P, Bradford W, Porter S, Blatt L, Seiwert SD, Zeuzem S.
J.W. Goethe Universität, Frankfurt, Germany.
Abstract
Danoprevir is a potent and selective inhibitor of the hepatitis C virus (HCV) NS3/4A serine protease. The present study assessed the safety, pharmacokinetics and antiviral activity of danoprevir in a randomized, placebo-controlled, 14-day multiple ascending dose study in patients with chronic HCV genotype 1 infection. Four cohorts of treatment-naïve (TN) patients (100 mg q12h, 100 mg q8h, 200 mg q12h, 200 mg q8h) and one cohort of non-responders (NR) to prior pegylated interferon alfa-ribavirin treatment (300 mg q12h) were investigated. RESULTS: Danoprevir was safe and well tolerated; adverse events were generally mild, transient and without association to treatment group or dose level. Danoprevir displayed a slightly more than proportional increase in exposure with increasing daily dose and was rapidly eliminated from the plasma compartment. Maximal decreases in HCV RNA were -3.9 log(10) IU/mL and -3.2 log(10) IU/mL in TN receiving 200 mg q8h and 200 mg q12h, respectively. End of treatment viral decline in these two cohorts was within 0.1 log(10) IU/mL of viral load nadir. HCV RNA reduction in NR was more modest than that observed in upper dose TN cohorts. The overall incidence of viral rebound was low (10/37) and was associated with R155K substitution in NS3 regardless of HCV subtype. CONCLUSION: Danoprevir was safe and well tolerated when administered for 14 days in patients with chronic HCV genotype 1 infection. Treatment resulted in sustained, multi-log(10) IU/mL reductions in HCV RNA in upper dose cohorts. These results support further clinical evaluation of danoprevir in patients with chronic HCV.
Copyright © 2010. Published by Elsevier B.V.
PMID: 21145848 [PubMed - as supplied by publisher]
Source
Adherence to treatment for recently acquired hepatitis C virus (HCV) infection among injecting drug users
J Hepatol. 2010 Nov 23. [Epub ahead of print]
Grebely J, Matthews GV, Hellard M, Shaw D, van Beek I, Petoumenos K, Alavi M, Yeung B, Haber PS, Lloyd AR, Kaldor JM, Dore GJ; for the ATAHC Study Group.
National Centre in HIV Epidemiology and Clinical Research, University of New South Wales (UNSW), Sydney.
Abstract
BACKGROUND AND AIMS: Adherence to HCV therapy impacts sustained virological response (SVR), but there are limited data on adherence, particularly among injecting drug users (IDUs). We assessed 80/80 adherence (>80% of PEG-IFN doses, >80% treatment), on-treatment adherence and treatment completion in a study of treatment of recent HCV infection (ATAHC)
METHODS: Participants with HCV received pegylated interferon (PEG-IFN) alfa-2a (180 μg/week, n=74); those with HCV/HIV received PEG-IFN alfa-2a with ribavirin (n=35). Everyone received 24 weeks of therapy. Logistic regression analyses were used to identify predictors of PEG-IFN 80/80 adherence.
RESULTS: Of 163, 109 received treatment (HCV, n=74; HCV/HIV, n=35), with 75% ever reporting IDU. The proportion with 80/80 PEG-IFN adherence was 82% (n=89). During treatment, 14% missed >1 dose (on-treatment adherence=99%). Completion of 0-4, 5-19, 20-23 and all 24 weeks of PEG-IFN therapy occurred in 10% (n=11), 14% (n=15), 6% (n=7) and 70% (n=76), respectively. Participants with no tertiary education were less likely to have 80/80 PEG-IFN adherence (AOR 0.29,P=0.045). IDU prior to or during treatment did not impact 80/80 PEG-IFN adherence. SVR was higher among those with >80/80 PEG-IFN adherence (67% vs. 35%,P=0.007), but similar among those with and without missed doses during therapy (73% vs. 60%,P=0.309). SVR in those discontinuing therapy between 0-4, 5-19, 20-23 and 24 weeks was 9%, 33%, 43% and 76%, respectively (P<0.001).
CONCLUSION: High adherence to treatment for recent HCV was observed, irrespective of IDU prior to, or during, therapy. Sub-optimal PEG-IFN exposure was mainly driven by early treatment discontinuation rather than missed doses during therapy.
Copyright © 2010. Published by Elsevier B.V.
PMID: 21145855 [PubMed - as supplied by publisher]
Source
Grebely J, Matthews GV, Hellard M, Shaw D, van Beek I, Petoumenos K, Alavi M, Yeung B, Haber PS, Lloyd AR, Kaldor JM, Dore GJ; for the ATAHC Study Group.
National Centre in HIV Epidemiology and Clinical Research, University of New South Wales (UNSW), Sydney.
Abstract
BACKGROUND AND AIMS: Adherence to HCV therapy impacts sustained virological response (SVR), but there are limited data on adherence, particularly among injecting drug users (IDUs). We assessed 80/80 adherence (>80% of PEG-IFN doses, >80% treatment), on-treatment adherence and treatment completion in a study of treatment of recent HCV infection (ATAHC)
METHODS: Participants with HCV received pegylated interferon (PEG-IFN) alfa-2a (180 μg/week, n=74); those with HCV/HIV received PEG-IFN alfa-2a with ribavirin (n=35). Everyone received 24 weeks of therapy. Logistic regression analyses were used to identify predictors of PEG-IFN 80/80 adherence.
RESULTS: Of 163, 109 received treatment (HCV, n=74; HCV/HIV, n=35), with 75% ever reporting IDU. The proportion with 80/80 PEG-IFN adherence was 82% (n=89). During treatment, 14% missed >1 dose (on-treatment adherence=99%). Completion of 0-4, 5-19, 20-23 and all 24 weeks of PEG-IFN therapy occurred in 10% (n=11), 14% (n=15), 6% (n=7) and 70% (n=76), respectively. Participants with no tertiary education were less likely to have 80/80 PEG-IFN adherence (AOR 0.29,P=0.045). IDU prior to or during treatment did not impact 80/80 PEG-IFN adherence. SVR was higher among those with >80/80 PEG-IFN adherence (67% vs. 35%,P=0.007), but similar among those with and without missed doses during therapy (73% vs. 60%,P=0.309). SVR in those discontinuing therapy between 0-4, 5-19, 20-23 and 24 weeks was 9%, 33%, 43% and 76%, respectively (P<0.001).
CONCLUSION: High adherence to treatment for recent HCV was observed, irrespective of IDU prior to, or during, therapy. Sub-optimal PEG-IFN exposure was mainly driven by early treatment discontinuation rather than missed doses during therapy.
Copyright © 2010. Published by Elsevier B.V.
PMID: 21145855 [PubMed - as supplied by publisher]
Source
Rapid Virological Response Is the Most Important Predictor of Sustained Virological Response Across Genotypes in Patients with Chronic Hepatitis C Virus Infection
J Hepatol. 2010 Nov 23. [Epub ahead of print]
Fried MW, Hadziyannis SJ, Shiffman ML, Messinger D, Zeuzem S.
University of North Carolina, Chapel Hill, USA.
Abstract
The probability of response to peginterferon and ribavirin is associated with numerous host and virological factors. Attainment of a rapid virological response (RVR), defined as undetectable HCV RNA at week 4 during treatment with peginterferon and ribavirin, is highly predictive of sustained virological response (SVR). The aim of the present study was to determine the relative importance of the kinetics of antiviral response compared to baseline host and virological factors for predicting SVR.
METHODS: A retrospective analysis of 1,383 patients, encompassing genotypes 1-4, treated with peginterferon alfa-2a and ribavirin was performed. Baseline characteristics were compared across HCV genotypes and pretreatment factors associated with RVR were identified. The relative significance of RVR compared to other baseline factors for predicting SVR was analyzed by multiple logistic regression analysis.
RESULTS: RVR was achieved by 16% of patients with genotype 1 and 71% and 60% of those with genotype 2 and 3, respectively. Among patients who achieved RVR, the rate of SVR was high across all genotypes and ranged from 88% to 100% (genotypes 1-4). Baseline factors predictive of RVR included genotype, younger age, lower initial viral load, higher ALT ratio, absence of advanced fibrosis, and younger age. Notably, the presence of RVR generated the highest odds ratio (5.47, 95% confidence interval 3.97-7.52) for predicting SVR in multiple logistic regression analysis of these factors.
CONCLUSIONS: Attainment of RVR varies by genotype and is associated with several baseline factors. Patients who achieve RVR have the highest rates of SVR, regardless of genotype. These findings have important implications for predicting and managing response-guided combination antiviral therapies.
Copyright © 2010. Published by Elsevier B.V.
PMID: 21145856 [PubMed - as supplied by publisher]
Source
Fried MW, Hadziyannis SJ, Shiffman ML, Messinger D, Zeuzem S.
University of North Carolina, Chapel Hill, USA.
Abstract
The probability of response to peginterferon and ribavirin is associated with numerous host and virological factors. Attainment of a rapid virological response (RVR), defined as undetectable HCV RNA at week 4 during treatment with peginterferon and ribavirin, is highly predictive of sustained virological response (SVR). The aim of the present study was to determine the relative importance of the kinetics of antiviral response compared to baseline host and virological factors for predicting SVR.
METHODS: A retrospective analysis of 1,383 patients, encompassing genotypes 1-4, treated with peginterferon alfa-2a and ribavirin was performed. Baseline characteristics were compared across HCV genotypes and pretreatment factors associated with RVR were identified. The relative significance of RVR compared to other baseline factors for predicting SVR was analyzed by multiple logistic regression analysis.
RESULTS: RVR was achieved by 16% of patients with genotype 1 and 71% and 60% of those with genotype 2 and 3, respectively. Among patients who achieved RVR, the rate of SVR was high across all genotypes and ranged from 88% to 100% (genotypes 1-4). Baseline factors predictive of RVR included genotype, younger age, lower initial viral load, higher ALT ratio, absence of advanced fibrosis, and younger age. Notably, the presence of RVR generated the highest odds ratio (5.47, 95% confidence interval 3.97-7.52) for predicting SVR in multiple logistic regression analysis of these factors.
CONCLUSIONS: Attainment of RVR varies by genotype and is associated with several baseline factors. Patients who achieve RVR have the highest rates of SVR, regardless of genotype. These findings have important implications for predicting and managing response-guided combination antiviral therapies.
Copyright © 2010. Published by Elsevier B.V.
PMID: 21145856 [PubMed - as supplied by publisher]
Source
Low Dose Ribavirin for Treatment of HCV Infected Thalassemia Major Patients; New Indications for Combination Therapy
J Hepatol. 2010 Nov 23. [Epub ahead of print]
Tabatabaei SV, Alavian SM, Keshvari M, Behnava B, Miri SM, Elizee PK, Zamani F, Kafi-Abad SA, Gharehbaghian A, Hajibeigy B, Lankarani KB.
Baqiyatallah University of Medical Sciences, Baqiyatallah Research Center for Gastroenterology and Liver Disease, Tehran, Iran.
Abstract
BACKGROUND AND AIMS: Treatment guidelines contraindicate ribavirin for treatment of hepatitis C virus (HCV) infection in thalassemia major patients. Nevertheless, the current evidence suggests that ribavirin might be tolerated by these patients. Despite this evidence, low dose ribavirin combination therapy has not been compared with peginterferon monotherapy in these patients so far.
MATERIAL AND METHODS: Two hundred eighty thalassemia patients with detectable HCV-RNA PCR (⩾50 IU/mL) and liver histology consistent with chronic HCV infection were self-assigned to receive peginterferon alfa-2a (n=81) monotherapy or its combination therapy with ribavirin, 600-800 mg QD, according to hemoglobin levels (n=199). Treatment experienced patients were eligible for this study.
RESULTS: Sustained virological response (SVR) was significantly higher in patients who received ribavirin (51% vs. 38% P=0.02). In multivariate regression, OR of ribavirin for prediction of SVR was 2.2 (95% CI 1.24-3.91). The SVR was significantly higher in the ribavirin group in subgroups of patients with more than 24 years of age, elevated ALT, ferritin<2006 ng/mL, previous treatment failure, genotype 1, positive history of splenectomy, fibrosis score of 0-4 HAI and viral load<600,000 IU/mL. Treatment discontinuations due to the safety concerns were comparable between the treatment groups (6.5 and 8%). Furthermore, transfusion intervals were almost halved in patients who received low dose ribavirin.
CONCLUSION: According to the present study, adult thalassemia patients with HCV infection can be treated successfully with low dose ribavirin. Hence, we strongly advise combination therapy in thalassemia patients with aforementioned clinical characteristics. Moreover, ribavirin does not seem to be beneficial in thalassemia patients below 18 years of age.
Copyright © 2010. Published by Elsevier B.V.
PMID: 21145858 [PubMed - as supplied by publisher]
Source
Tabatabaei SV, Alavian SM, Keshvari M, Behnava B, Miri SM, Elizee PK, Zamani F, Kafi-Abad SA, Gharehbaghian A, Hajibeigy B, Lankarani KB.
Baqiyatallah University of Medical Sciences, Baqiyatallah Research Center for Gastroenterology and Liver Disease, Tehran, Iran.
Abstract
BACKGROUND AND AIMS: Treatment guidelines contraindicate ribavirin for treatment of hepatitis C virus (HCV) infection in thalassemia major patients. Nevertheless, the current evidence suggests that ribavirin might be tolerated by these patients. Despite this evidence, low dose ribavirin combination therapy has not been compared with peginterferon monotherapy in these patients so far.
MATERIAL AND METHODS: Two hundred eighty thalassemia patients with detectable HCV-RNA PCR (⩾50 IU/mL) and liver histology consistent with chronic HCV infection were self-assigned to receive peginterferon alfa-2a (n=81) monotherapy or its combination therapy with ribavirin, 600-800 mg QD, according to hemoglobin levels (n=199). Treatment experienced patients were eligible for this study.
RESULTS: Sustained virological response (SVR) was significantly higher in patients who received ribavirin (51% vs. 38% P=0.02). In multivariate regression, OR of ribavirin for prediction of SVR was 2.2 (95% CI 1.24-3.91). The SVR was significantly higher in the ribavirin group in subgroups of patients with more than 24 years of age, elevated ALT, ferritin<2006 ng/mL, previous treatment failure, genotype 1, positive history of splenectomy, fibrosis score of 0-4 HAI and viral load<600,000 IU/mL. Treatment discontinuations due to the safety concerns were comparable between the treatment groups (6.5 and 8%). Furthermore, transfusion intervals were almost halved in patients who received low dose ribavirin.
CONCLUSION: According to the present study, adult thalassemia patients with HCV infection can be treated successfully with low dose ribavirin. Hence, we strongly advise combination therapy in thalassemia patients with aforementioned clinical characteristics. Moreover, ribavirin does not seem to be beneficial in thalassemia patients below 18 years of age.
Copyright © 2010. Published by Elsevier B.V.
PMID: 21145858 [PubMed - as supplied by publisher]
Source
Role of a cirrhosis risk score for the early prediction of fibrosis progression in hepatitis C patients with minimal liver disease
J Hepatol. 2010 Nov 23. [Epub ahead of print]
Trépo E, Potthoff A, Pradat P, Bakshi R, Young B, Lagier R, Moreno C, Verset L, Cross R, Degré D, Lemmers A, Gustot T, Berthillon P, Rosenberg W, Trépo C, Sninsky J, Adler M, Wedemeyer H.
Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium; Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme Hospital, Université libre de Bruxelles, Brussels, Belgium.
Abstract
BACKGROUND AND AIMS: Fibrosis progression in patients with chronic hepatitis C (CHC) is highly variable. A Cirrhosis Risk Score (CRS) based on seven genetic variants has been recently developed for identifying patients at risk for cirrhosis. The objective of this study was to assess the role of the CRS for the early prediction of fibrosis progression in CHC patients with mild liver fibrosis. In addition, we evaluated the potential benefit, for prediction accuracy, of a recently described non-invasive fibrosis staging assay, the Enhanced Liver Fibrosis (ELF) test.
METHODS: Two separate cohorts of HCV patients (Brussels, Belgium/Hannover, Germany) were retrospectively analyzed. Only patients with a fibrosis Ishak or METAVIR score of F0-F1 at baseline were included. Patients were classified as progressors if they showed an increase >=2 fibrosis stages at the second histological evaluation after a follow-up >=5 years. The CRS was calculated locally. Genotyping was performed by PCR and oligonucleotide ligation with the resulting signal detected with a Luminex® 200TM and computer analysis.
RESULTS: In Brussels, 12/25 patients progressed (48%); similarly in Hannover, 16/31 (52%) patients progressed. In both sample sets, the CRS was significantly associated with fibrosis progression (p=0.050 in Brussels; p=0.018 in Hannover). The ELF test was only a significant predictor in Hannover (p=0.015). In multivariate analysis the CRS remained the only variable associated with fibrosis progression (Odds-ratio= 2.23, 95%CI 1.21-4.11 p=0.01).
CONCLUSIONS: Although conducted on a limited number of patients, this study in two independent centres confirms that the CRS predicts fibrosis progression in initially mild CHC.
Copyright © 2010. Published by Elsevier B.V.
PMID: 21145859 [PubMed - as supplied by publisher]
Source
Trépo E, Potthoff A, Pradat P, Bakshi R, Young B, Lagier R, Moreno C, Verset L, Cross R, Degré D, Lemmers A, Gustot T, Berthillon P, Rosenberg W, Trépo C, Sninsky J, Adler M, Wedemeyer H.
Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium; Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme Hospital, Université libre de Bruxelles, Brussels, Belgium.
Abstract
BACKGROUND AND AIMS: Fibrosis progression in patients with chronic hepatitis C (CHC) is highly variable. A Cirrhosis Risk Score (CRS) based on seven genetic variants has been recently developed for identifying patients at risk for cirrhosis. The objective of this study was to assess the role of the CRS for the early prediction of fibrosis progression in CHC patients with mild liver fibrosis. In addition, we evaluated the potential benefit, for prediction accuracy, of a recently described non-invasive fibrosis staging assay, the Enhanced Liver Fibrosis (ELF) test.
METHODS: Two separate cohorts of HCV patients (Brussels, Belgium/Hannover, Germany) were retrospectively analyzed. Only patients with a fibrosis Ishak or METAVIR score of F0-F1 at baseline were included. Patients were classified as progressors if they showed an increase >=2 fibrosis stages at the second histological evaluation after a follow-up >=5 years. The CRS was calculated locally. Genotyping was performed by PCR and oligonucleotide ligation with the resulting signal detected with a Luminex® 200TM and computer analysis.
RESULTS: In Brussels, 12/25 patients progressed (48%); similarly in Hannover, 16/31 (52%) patients progressed. In both sample sets, the CRS was significantly associated with fibrosis progression (p=0.050 in Brussels; p=0.018 in Hannover). The ELF test was only a significant predictor in Hannover (p=0.015). In multivariate analysis the CRS remained the only variable associated with fibrosis progression (Odds-ratio= 2.23, 95%CI 1.21-4.11 p=0.01).
CONCLUSIONS: Although conducted on a limited number of patients, this study in two independent centres confirms that the CRS predicts fibrosis progression in initially mild CHC.
Copyright © 2010. Published by Elsevier B.V.
PMID: 21145859 [PubMed - as supplied by publisher]
Source
Predictors and effects of alcohol use on liver function among young HCV-infected injection drug users in a behavioral intervention
J Hepatol. 2010 Nov 24. [Epub ahead of print]
Drumright LN, Hagan H, Thomas DL, Latka MH, Golub ET, Garfein RS, Clapp JD, Campbell JV, Bonner S, Kapadia F, Thiel TK, Strathdee SA.
At the time of work on study: University of California, San Diego, Department of Medicine, Division of Global Public Health, La Jolla, CA.
Abstract
BACKGROUND & AIMS: Hepatitis C virus (HCV) screening can provide opportunities to reduce disease progression through counseling against alcohol use, but empirical data on this issue are sparse. We determined the efficacy of a behavioral intervention in reducing alcohol use among young, HCV-infected injection drug users (IDUs) (n=355) and assessed whether changes in liver enzymes were associated with changes in alcohol consumption.
METHODS: Both the intervention and attention-control groups were counseled to avoid alcohol use, but the intervention group received enhanced counseling. Logistic regression, ANOVA, and continuous time Markov models were used to identify factors associated with alcohol use, changes in mean ALT and AST levels and change in alcohol use post-intervention.
RESULTS: Six months post-intervention, alcohol abstinence increased 22.7% in both groups, with no difference by intervention arm. Transition from alcohol use to abstinence was associated with a decrease in liver enzymes, with a marginally greater decrease in the intervention group (p=0.05 for ALT; p=0.06 for AST). In multivariate Markov models, those who used marijuana transitioned from alcohol abstinence to consumption more rapidly than non-users (RR=3.11); those who were homeless transitioned more slowly to alcohol abstinence (RR=0.47); and those who had ever received a clinical diagnosis of liver disease transitioned more rapidly to abstinence (RR=1.88).
CONCLUSIONS: Although, behavioral counseling to reduce alcohol consumption among HCV-infected IDUs had a modest effect, reductions in alcohol consumption were associated with marked improvements in liver function. Interventions to reduce alcohol use among HCV-infected IDUs may benefit from being integrated into clinical care and monitoring of HCV infection.
Copyright © 2010. Published by Elsevier B.V.
PMID: 21145862 [PubMed - as supplied by publisher]
Source
Drumright LN, Hagan H, Thomas DL, Latka MH, Golub ET, Garfein RS, Clapp JD, Campbell JV, Bonner S, Kapadia F, Thiel TK, Strathdee SA.
At the time of work on study: University of California, San Diego, Department of Medicine, Division of Global Public Health, La Jolla, CA.
Abstract
BACKGROUND & AIMS: Hepatitis C virus (HCV) screening can provide opportunities to reduce disease progression through counseling against alcohol use, but empirical data on this issue are sparse. We determined the efficacy of a behavioral intervention in reducing alcohol use among young, HCV-infected injection drug users (IDUs) (n=355) and assessed whether changes in liver enzymes were associated with changes in alcohol consumption.
METHODS: Both the intervention and attention-control groups were counseled to avoid alcohol use, but the intervention group received enhanced counseling. Logistic regression, ANOVA, and continuous time Markov models were used to identify factors associated with alcohol use, changes in mean ALT and AST levels and change in alcohol use post-intervention.
RESULTS: Six months post-intervention, alcohol abstinence increased 22.7% in both groups, with no difference by intervention arm. Transition from alcohol use to abstinence was associated with a decrease in liver enzymes, with a marginally greater decrease in the intervention group (p=0.05 for ALT; p=0.06 for AST). In multivariate Markov models, those who used marijuana transitioned from alcohol abstinence to consumption more rapidly than non-users (RR=3.11); those who were homeless transitioned more slowly to alcohol abstinence (RR=0.47); and those who had ever received a clinical diagnosis of liver disease transitioned more rapidly to abstinence (RR=1.88).
CONCLUSIONS: Although, behavioral counseling to reduce alcohol consumption among HCV-infected IDUs had a modest effect, reductions in alcohol consumption were associated with marked improvements in liver function. Interventions to reduce alcohol use among HCV-infected IDUs may benefit from being integrated into clinical care and monitoring of HCV infection.
Copyright © 2010. Published by Elsevier B.V.
PMID: 21145862 [PubMed - as supplied by publisher]
Source
Indications and limitations for aged patients with chronic hepatitis C in pegylated interferon alfa-2b plus ribavirin combination therapy
J Hepatol. 2010 Dec 8. [Epub ahead of print]
Oze T, Hiramatsu N, Yakushijin T, Mochizuki K, Oshita M, Hagiwara H, Mita E, Ito T, Fukui H, Inui Y, Hijioka T, Inada M, Kaytayama K, Tamura S, Yoshihara H, Inoue A, Imai Y, Kato M, Miyagi T, Yoshida Y, Tatsumi T, Kiso S, Kanto T, Kasahara A, Takehara T, Hayashi N.
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan.
Abstract
BACKGROUND & AIMS: This study investigated the efficacy and adverse effects of pegylated interferon (Peg-IFN) plus ribavirin therapy in aged patients with chronic hepatitis C (CH-C).
METHODS: A total of 1040 naïve patients with CH-C (genotype 1, n=759; genotype 2, n=281), of whom 240 (23%) over 65years old (y.o.), were treated with Peg-IFN alfa-2b plus ribavirin and assessed after being classified into five categories, according to age.
RESULTS: The discontinuance rate was higher for patients over 70 y.o. (36%), the most common reason being anemia. In the presence of genotype 1, the SVR rate was similar (42-46%) among patients under 65 y.o. and declined (26-29%) among patients over 65 y.o. For patients over 65 y.o., being male (Odds ratio, OR, 3.5, p=0.035) and EVR (OR, 83.3, p<0.001) were significant factors for SVR, in multivariate analysis. The Peg-IFN dose was related to EVR, and when EVR was attained, 76-86% of patients over 65 y.o. achieved SVR. SVR was not achieved (0/35, 0/38, respectively) if a 1-log decrease and a 2-log decrease were not attained at week 4 and week 8, respectively. In the presence of genotype 2, the SVR rate was similar (70-71%) among patients under 70 y.o. and declined among patients over 70 y.o. (43%).
CONCLUSIONS: Aged patients up to 65 y.o. with genotype 1 and 70 y.o. with genotype 2 can be candidates for pegylated interferon (Peg-IFN) plus ribavirin therapy. The response-guided therapy can be applied for aged patients with genotype 1.
Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
PMID: 21145907 [PubMed - as supplied by publisher]
Source
Oze T, Hiramatsu N, Yakushijin T, Mochizuki K, Oshita M, Hagiwara H, Mita E, Ito T, Fukui H, Inui Y, Hijioka T, Inada M, Kaytayama K, Tamura S, Yoshihara H, Inoue A, Imai Y, Kato M, Miyagi T, Yoshida Y, Tatsumi T, Kiso S, Kanto T, Kasahara A, Takehara T, Hayashi N.
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan.
Abstract
BACKGROUND & AIMS: This study investigated the efficacy and adverse effects of pegylated interferon (Peg-IFN) plus ribavirin therapy in aged patients with chronic hepatitis C (CH-C).
METHODS: A total of 1040 naïve patients with CH-C (genotype 1, n=759; genotype 2, n=281), of whom 240 (23%) over 65years old (y.o.), were treated with Peg-IFN alfa-2b plus ribavirin and assessed after being classified into five categories, according to age.
RESULTS: The discontinuance rate was higher for patients over 70 y.o. (36%), the most common reason being anemia. In the presence of genotype 1, the SVR rate was similar (42-46%) among patients under 65 y.o. and declined (26-29%) among patients over 65 y.o. For patients over 65 y.o., being male (Odds ratio, OR, 3.5, p=0.035) and EVR (OR, 83.3, p<0.001) were significant factors for SVR, in multivariate analysis. The Peg-IFN dose was related to EVR, and when EVR was attained, 76-86% of patients over 65 y.o. achieved SVR. SVR was not achieved (0/35, 0/38, respectively) if a 1-log decrease and a 2-log decrease were not attained at week 4 and week 8, respectively. In the presence of genotype 2, the SVR rate was similar (70-71%) among patients under 70 y.o. and declined among patients over 70 y.o. (43%).
CONCLUSIONS: Aged patients up to 65 y.o. with genotype 1 and 70 y.o. with genotype 2 can be candidates for pegylated interferon (Peg-IFN) plus ribavirin therapy. The response-guided therapy can be applied for aged patients with genotype 1.
Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
PMID: 21145907 [PubMed - as supplied by publisher]
Source
Impact of donor and recipient IL28B rs12979860 genotypes on hepatitis C virus liver graft reinfection
J Hepatol. 2010 Dec 10. [Epub ahead of print]
Lange CM, Moradpour D, Doehring A, Lehr HA, Müllhaupt B, Bibert S, Bochud PY, Antonino AT, Pascual M, Farnik H, Shi Y, Bechstein WO, Moench C, Hansmann ML, Sarrazin C, Lötsch J, Zeuzem S, Hofmann WP.
Medizinische Klinik 1, Germany; Centre Hospitalier Universitaire Vaudois, University of Lausanne, Rue Bugnon 46, CH-1010 Lausanne, Switzerland.
Abstract
BACKGROUND AND AIM: Recent studies described a major impact of genetic variations near the IL28B gene on the natural course and outcome of antiviral therapy in chronic hepatitis C. We therefore aimed to explore the impact of donor and recipient genotypes of these polymorphisms on hepatitis C virus (HCV) liver graft reinfection.
METHODS: Donor and recipient genotypes of IL28B rs12979860C>T single nucleotide polymorphism were determined in 91 patients with HCV liver graft reinfection, 47 of which were treated with pegylated interferon-α(PEG-IFN-α) and ribavirin. IL28B genetic polymorphisms were correlated with the natural course and treatment outcome of recurrent hepatitis C.
RESULTS: Patients requiring liver transplantation due to end-stage chronic hepatitis C appeared to be selected towards the adverse genotypes rs12979860CT/TT compared to non-transplanted HCV-infected patients (p=0.046). Patients with the donor genotype rs12979860CC had higher peak ALT and HCV RNA serum concentrations than those with CT/TT (p=0.04 and 0.06, respectively). No associations were observed between ALT / HCV RNA serum concentrations and recipient genotypes (p>0.3). More important, donor IL28B rs12979860 CC vs. CT/TT genotypes were associated with rapid, complete early, and sustained virologic response (RVR, cEVR, SVR) to treatment with PEG-IFN-α and ribavirin (p=0.003, 0.0012, 0.008, respectively), but weaker associations of recipient genotypes with RVR, cEVR and SVR were observed as well (p=0.0046, 0.115, 0.118, respectively).
CONCLUSIONS: We provide evidence for a dominant, but not exclusive impact of the donor rather than the recipient IL28B genetic background on the natural course and treatment outcome of HCV liver graft reinfection.
Copyright © 2010. Published by Elsevier B.V.
PMID: 21147186 [PubMed - as supplied by publisher]
Source
Lange CM, Moradpour D, Doehring A, Lehr HA, Müllhaupt B, Bibert S, Bochud PY, Antonino AT, Pascual M, Farnik H, Shi Y, Bechstein WO, Moench C, Hansmann ML, Sarrazin C, Lötsch J, Zeuzem S, Hofmann WP.
Medizinische Klinik 1, Germany; Centre Hospitalier Universitaire Vaudois, University of Lausanne, Rue Bugnon 46, CH-1010 Lausanne, Switzerland.
Abstract
BACKGROUND AND AIM: Recent studies described a major impact of genetic variations near the IL28B gene on the natural course and outcome of antiviral therapy in chronic hepatitis C. We therefore aimed to explore the impact of donor and recipient genotypes of these polymorphisms on hepatitis C virus (HCV) liver graft reinfection.
METHODS: Donor and recipient genotypes of IL28B rs12979860C>T single nucleotide polymorphism were determined in 91 patients with HCV liver graft reinfection, 47 of which were treated with pegylated interferon-α(PEG-IFN-α) and ribavirin. IL28B genetic polymorphisms were correlated with the natural course and treatment outcome of recurrent hepatitis C.
RESULTS: Patients requiring liver transplantation due to end-stage chronic hepatitis C appeared to be selected towards the adverse genotypes rs12979860CT/TT compared to non-transplanted HCV-infected patients (p=0.046). Patients with the donor genotype rs12979860CC had higher peak ALT and HCV RNA serum concentrations than those with CT/TT (p=0.04 and 0.06, respectively). No associations were observed between ALT / HCV RNA serum concentrations and recipient genotypes (p>0.3). More important, donor IL28B rs12979860 CC vs. CT/TT genotypes were associated with rapid, complete early, and sustained virologic response (RVR, cEVR, SVR) to treatment with PEG-IFN-α and ribavirin (p=0.003, 0.0012, 0.008, respectively), but weaker associations of recipient genotypes with RVR, cEVR and SVR were observed as well (p=0.0046, 0.115, 0.118, respectively).
CONCLUSIONS: We provide evidence for a dominant, but not exclusive impact of the donor rather than the recipient IL28B genetic background on the natural course and treatment outcome of HCV liver graft reinfection.
Copyright © 2010. Published by Elsevier B.V.
PMID: 21147186 [PubMed - as supplied by publisher]
Source
IL28B inhibits Hepatitis C virus replication through the JAK-STAT pathway
J Hepatol. 2010 Dec 10. [Epub ahead of print]
Zhang L, Jilg N, Shao RX, Lin W, Fusco DN, Zhao H, Goto K, Peng LF, Chen WC, Chung RT.
Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Abstract
BACKGROUND AND AIMS: The combination of pegylated interferon (IFN) α and ribavirin (RBV) is standard therapy for patients with chronic HCV infection. However, it produces a sustained virologic response (SVR) in only half of treated individuals and is associated with significant side effects. Recently several single-nucleotide polymorphisms (SNPs) near the IL28B locus, also known as IFNλ3, were identified to be strong predictors of SVR in patients receiving PEG-IFN and RBV. We sought to determine whether IL28B was capable of inhibiting HCV replication and to determine the pathway by which IL28B exhibits anti-HCV activity.
METHODS: Using the full-length HCV replicon OR6 and the infectious HCV clones JFH1 and Jc1, we assessed the anti-HCV effect of IL28B on HCV and characterized the key steps of the JAK-STAT pathway by real time PCR, luciferase assay, and Western blot. Finally, we evaluated the anti-HCV effect of IL28B in the presence of JAK-STAT pathway inhibitors such as blocking antibodies, a pharmacological inhibitor and siRNAs.
RESULTS: We found that IL28B inhibits HCV replication in a dose- and time- dependent manner. Like IFNα, IL28B induces the phosphorylation of STAT1 and STAT2, ISRE-driven transcription, and expression of known ISGs. The anti-HCV effects of IL28A, IL28B and IL29 were abrogated by an IL10R2 blocking antibody, a pharmacological inhibitor of JAK1/TYK2, and by siRNA against IL28R1, STAT1, STAT2 and IRF9.
CONCLUSIONS: Our data demonstrate that IL28A, IL28B and IL29 signal through the JAK-STAT pathway to inhibit HCV. These data suggest possible applications of new approaches in HCV treatment.
Copyright © 2010. Published by Elsevier B.V.
PMID: 21147189 [PubMed - as supplied by publisher]
Source
Zhang L, Jilg N, Shao RX, Lin W, Fusco DN, Zhao H, Goto K, Peng LF, Chen WC, Chung RT.
Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Abstract
BACKGROUND AND AIMS: The combination of pegylated interferon (IFN) α and ribavirin (RBV) is standard therapy for patients with chronic HCV infection. However, it produces a sustained virologic response (SVR) in only half of treated individuals and is associated with significant side effects. Recently several single-nucleotide polymorphisms (SNPs) near the IL28B locus, also known as IFNλ3, were identified to be strong predictors of SVR in patients receiving PEG-IFN and RBV. We sought to determine whether IL28B was capable of inhibiting HCV replication and to determine the pathway by which IL28B exhibits anti-HCV activity.
METHODS: Using the full-length HCV replicon OR6 and the infectious HCV clones JFH1 and Jc1, we assessed the anti-HCV effect of IL28B on HCV and characterized the key steps of the JAK-STAT pathway by real time PCR, luciferase assay, and Western blot. Finally, we evaluated the anti-HCV effect of IL28B in the presence of JAK-STAT pathway inhibitors such as blocking antibodies, a pharmacological inhibitor and siRNAs.
RESULTS: We found that IL28B inhibits HCV replication in a dose- and time- dependent manner. Like IFNα, IL28B induces the phosphorylation of STAT1 and STAT2, ISRE-driven transcription, and expression of known ISGs. The anti-HCV effects of IL28A, IL28B and IL29 were abrogated by an IL10R2 blocking antibody, a pharmacological inhibitor of JAK1/TYK2, and by siRNA against IL28R1, STAT1, STAT2 and IRF9.
CONCLUSIONS: Our data demonstrate that IL28A, IL28B and IL29 signal through the JAK-STAT pathway to inhibit HCV. These data suggest possible applications of new approaches in HCV treatment.
Copyright © 2010. Published by Elsevier B.V.
PMID: 21147189 [PubMed - as supplied by publisher]
Source
Meeting vaccination quality measures for hepatitis A and B virus in patients with chronic hepatitis C infection
Hepatology. 2010 Oct 6. [Epub ahead of print]
Kramer JR, Hachem CY, Kanwal F, Mei M, El-Serag HB.
Houston VA Health Services Research #38; Development Center of Excellence, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX.
Abstract
Coinfection with hepatitis A virus (HAV) or hepatitis B virus (HBV) in patients with chronic hepatitis C virus (HCV) is associated with increased morbidity and mortality. The Center for Medicare and Medicaid Services has identified HAV and HBV vaccination as a priority area for quality measurement in HCV. It is unclear to what extent patients with HCV meet these recommendations. We used national data from the Department of Veterans Affairs HCV Clinical Case Registry to evaluate the prevalence and predictors of meeting the quality measure (QM) of receiving vaccination or documented immunity to HAV and HBV in patients with chronic HCV. We identified 88,456 patients who had overall vaccination rates of 21.9% and 20.7% for HBV and HAV, respectively. The QM rates were 57.0% and 45.5% for HBV and HAV, respectively. Patients who were nonwhite or who had elevated alanine aminotransferase levels, cirrhosis, or human immunodeficiency virus were more likely to meet the HBV QM. Factors related to HCV care were also determinants of meeting the HBV QM. These factors included receiving a specialist consult, genotype testing, or HCV treatment. Patients who were older, had psychosis, and had a higher comorbidity score were less likely to meet the HBV QM. With a few exceptions, similar variables were related to meeting the HAV QM. The incidence of superinfection with acute HBV and HAV was low, but it was significantly lower in patients who received vaccination than in those who did not. Conclusion: Quality measure rates for HAV and HBV are suboptimal for patients with chronic HCV. In addition, several patient-related factors and receiving HCV-related care are associated with a higher likelihood of meeting QMs. (HEPATOLOGY 2010;).
PMID: 21157783 [PubMed - as supplied by publisher]
Source
Kramer JR, Hachem CY, Kanwal F, Mei M, El-Serag HB.
Houston VA Health Services Research #38; Development Center of Excellence, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX.
Abstract
Coinfection with hepatitis A virus (HAV) or hepatitis B virus (HBV) in patients with chronic hepatitis C virus (HCV) is associated with increased morbidity and mortality. The Center for Medicare and Medicaid Services has identified HAV and HBV vaccination as a priority area for quality measurement in HCV. It is unclear to what extent patients with HCV meet these recommendations. We used national data from the Department of Veterans Affairs HCV Clinical Case Registry to evaluate the prevalence and predictors of meeting the quality measure (QM) of receiving vaccination or documented immunity to HAV and HBV in patients with chronic HCV. We identified 88,456 patients who had overall vaccination rates of 21.9% and 20.7% for HBV and HAV, respectively. The QM rates were 57.0% and 45.5% for HBV and HAV, respectively. Patients who were nonwhite or who had elevated alanine aminotransferase levels, cirrhosis, or human immunodeficiency virus were more likely to meet the HBV QM. Factors related to HCV care were also determinants of meeting the HBV QM. These factors included receiving a specialist consult, genotype testing, or HCV treatment. Patients who were older, had psychosis, and had a higher comorbidity score were less likely to meet the HBV QM. With a few exceptions, similar variables were related to meeting the HAV QM. The incidence of superinfection with acute HBV and HAV was low, but it was significantly lower in patients who received vaccination than in those who did not. Conclusion: Quality measure rates for HAV and HBV are suboptimal for patients with chronic HCV. In addition, several patient-related factors and receiving HCV-related care are associated with a higher likelihood of meeting QMs. (HEPATOLOGY 2010;).
PMID: 21157783 [PubMed - as supplied by publisher]
Source
December 17, 2010
Progression of initially mild hepatic fibrosis in patients with chronic hepatitis C infection
J Viral Hepat. 2011 Jan;18(1):17-22. doi: 10.1111/j.1365-2893.2009.01262.x.
Williams MJ, Lang-Lenton M; on behalf of the Trent HCV Study Group.
Nottingham Digestive Diseases Centre, Nottingham University Hospital, Nottingham, UK.
Abstract
Summary. A significant number of patients with chronic hepatitis C infection have minimal fibrosis at presentation. Although the short-term outlook for such patients is good, there are limited data available on long-term progression. We assessed the risk of fibrosis progression in 282 patients with chronic hepatitis C with Ishak stage 0 or 1 fibrosis on initial liver biopsy. Progression of fibrosis stage occurred in 118 patients (42%) over a median interval of 52.5 months. Thirteen (5%) progressed to severe (Ishak stage 4 or more) fibrosis. Progression was significantly associated with both age at initial biopsy [odds ratio (OR) for progression of 1.31 per 10 year increase in age] and median alanine transaminase (ALT) levels during follow-up (OR of 1.06 per 10 IU/L increase). There was no significant association with gender, histological inflammatory grade, hepatic steatosis or body mass index. We conclude that hepatitis C with initially mild fibrosis does progress in a substantial proportion of patients and should not be viewed as a benign disease. Early antiviral therapy should be considered in older patients and those with high ALT levels.
© 2010 Blackwell Publishing Ltd.
PMID: 20088889 [PubMed - as supplied by publisher]
Source
Williams MJ, Lang-Lenton M; on behalf of the Trent HCV Study Group.
Nottingham Digestive Diseases Centre, Nottingham University Hospital, Nottingham, UK.
Abstract
Summary. A significant number of patients with chronic hepatitis C infection have minimal fibrosis at presentation. Although the short-term outlook for such patients is good, there are limited data available on long-term progression. We assessed the risk of fibrosis progression in 282 patients with chronic hepatitis C with Ishak stage 0 or 1 fibrosis on initial liver biopsy. Progression of fibrosis stage occurred in 118 patients (42%) over a median interval of 52.5 months. Thirteen (5%) progressed to severe (Ishak stage 4 or more) fibrosis. Progression was significantly associated with both age at initial biopsy [odds ratio (OR) for progression of 1.31 per 10 year increase in age] and median alanine transaminase (ALT) levels during follow-up (OR of 1.06 per 10 IU/L increase). There was no significant association with gender, histological inflammatory grade, hepatic steatosis or body mass index. We conclude that hepatitis C with initially mild fibrosis does progress in a substantial proportion of patients and should not be viewed as a benign disease. Early antiviral therapy should be considered in older patients and those with high ALT levels.
© 2010 Blackwell Publishing Ltd.
PMID: 20088889 [PubMed - as supplied by publisher]
Source
Enhanced Liver Fibrosis (ELF) test accurately identifies liver fibrosis in patients with chronic hepatitis C
J Viral Hepat. 2011 Jan;18(1):23-31. doi: 10.1111/j.1365-2893.2009.01263.x.
Parkes J, Guha IN, Roderick P, Harris S, Cross R, Manos MM, Irving W, Zaitoun A, Wheatley M, Ryder S, Rosenberg W.
Public Health Sciences & Medical Statistics, University of Southampton, Southampton Nottingham Digestive Diseases Centre Biomedical Research Unit, University of Nottingham iQur Ltd, Southampton General Hospital, Southampton, UK Kaiser Permanente Division of Research; Oakland, CA, USA Division of Microbiology, University Hospital, Queen's Medical Centre, Nottingham Department of Histopathology, University Hospital Queens Medical Centre, Nottingham Division of Gastroenterology, Queens Medical Centre, Nottingham; Centre for Hepatology, University College London, London, UK.
Abstract
Summary. Assessment of liver fibrosis is important in determining prognosis and evaluating interventions. Due to limitations of accuracy and patient hazard of liver biopsy, non-invasive methods have been sought to provide information on liver fibrosis, including the European liver fibrosis (ELF) test, shown to have good diagnostic accuracy for the detection of moderate and severe fibrosis. Access to independent cohorts of patients has provided an opportunity to explore if this test could be simplified. This paper reports the simplification of the ELF test and its ability to identity severity of liver fibrosis in external validation studies in patients with chronic hepatitis C (CHC). Paired biopsy and serum samples from 347 naïve patients with CHC in three independent cohorts were analysed. Diagnostic performance characteristics were derived (AUROC, sensitivity and specificity, predictive values), and clinical utility modelling performed to determine the proportion of biopsies that could have been avoided if ELF test was used in this patient group. It was possible to simplify the original ELF test without loss of performance and the new algorithm is reported. The simplified ELF test was able to predict severe fibrosis [pooled AUROC of 0.85 (95% CI 0.81-0.89)] and using clinical utility modelling to predict severe fibrosis (Ishak stages 4-6; METAVIR stages 3 and 4) 81% of biopsies could have been avoided (65% correctly). Issues of spectrum effect in diagnostic test evaluations are discussed. In chronic hepatitis C a simplified ELF test can detect severe liver fibrosis with good accuracy.
© 2010 Blackwell Publishing Ltd.
PMID: 20196799 [PubMed - as supplied by publisher]
Source
Parkes J, Guha IN, Roderick P, Harris S, Cross R, Manos MM, Irving W, Zaitoun A, Wheatley M, Ryder S, Rosenberg W.
Public Health Sciences & Medical Statistics, University of Southampton, Southampton Nottingham Digestive Diseases Centre Biomedical Research Unit, University of Nottingham iQur Ltd, Southampton General Hospital, Southampton, UK Kaiser Permanente Division of Research; Oakland, CA, USA Division of Microbiology, University Hospital, Queen's Medical Centre, Nottingham Department of Histopathology, University Hospital Queens Medical Centre, Nottingham Division of Gastroenterology, Queens Medical Centre, Nottingham; Centre for Hepatology, University College London, London, UK.
Abstract
Summary. Assessment of liver fibrosis is important in determining prognosis and evaluating interventions. Due to limitations of accuracy and patient hazard of liver biopsy, non-invasive methods have been sought to provide information on liver fibrosis, including the European liver fibrosis (ELF) test, shown to have good diagnostic accuracy for the detection of moderate and severe fibrosis. Access to independent cohorts of patients has provided an opportunity to explore if this test could be simplified. This paper reports the simplification of the ELF test and its ability to identity severity of liver fibrosis in external validation studies in patients with chronic hepatitis C (CHC). Paired biopsy and serum samples from 347 naïve patients with CHC in three independent cohorts were analysed. Diagnostic performance characteristics were derived (AUROC, sensitivity and specificity, predictive values), and clinical utility modelling performed to determine the proportion of biopsies that could have been avoided if ELF test was used in this patient group. It was possible to simplify the original ELF test without loss of performance and the new algorithm is reported. The simplified ELF test was able to predict severe fibrosis [pooled AUROC of 0.85 (95% CI 0.81-0.89)] and using clinical utility modelling to predict severe fibrosis (Ishak stages 4-6; METAVIR stages 3 and 4) 81% of biopsies could have been avoided (65% correctly). Issues of spectrum effect in diagnostic test evaluations are discussed. In chronic hepatitis C a simplified ELF test can detect severe liver fibrosis with good accuracy.
© 2010 Blackwell Publishing Ltd.
PMID: 20196799 [PubMed - as supplied by publisher]
Source
WHAT KINDS OF DOCTORS TREAT LIVER DISEASE?
Written by Melissa Palmer, MD
Melissa Palmer, MD is the author of " Dr. Melissa Palmer's Guide of Hepatitis and Liver Disease". (Published 2004. Penguin Putnam).
There are many different kinds of doctors who evaluate and treat people with liver disorders. First, there is the family physician or internist. These doctors are also referred to as primary care physicians (PCPs). They are often the first ones to discover that something is wrong with the liver. From there, the patient is customarily referred to a specialist—either a gastroenterologist, hepatologist, or infectious disease specialist—for further evaluation and treatment. This specialist may be in a practice located at an academic institution or in a private practice located in a community setting. The difference between the various types of doctors a patient with liver disease encounters may sometimes be confusing. Hopefully, this section will clarify these differences in order to eliminate any future confusion.
The Medical Doctor (MD)
Medical Doctors (MDs) are physicians who have successfully completed four years of medical school training. After graduating from medical school, these doctors must complete a minimum of one additional year of training in a hospital in what is known as an internship. They must then pass a state-licensing exam in order to practice medicine in that state. After obtaining their license, they have the right to practice medicine in that state. However, many doctors choose to continue their training in a hospital by undergoing a residency—typically an additional two years.
After completing their residency, these doctors must take an exam in order to become board certified in a specialty, such as family medicine or internal medicine. Doctors may practice medicine whether or not they pass this exam. Doctors who become family doctors or internists have general knowledge in all areas of medicine including the heart, lungs, kidneys, stomach, intestines, and liver. At this time, a doctor may decide to undergo additional specialty training, known as a fellowship, in a specific area of internal medicine, such as gastroenterology, hepatology, or infectious diseases, in order to become an expert in these areas.
The Doctor of Osteopathy (DO)
Doctors of osteopathy (DOs) are commonly referred to as osteopaths. These are doctors who graduated from a four-year osteopathic school. They must also complete a one-year internship in a hospital in order to be eligible to obtain a license to practice medicine. Osteopaths can also choose to undergo an additional two-year residency, and may thereafter undergo specialty training in a specific area of medicine.
Osteopaths tend to focus on treating “the body as a whole,” particularly on the body’s ability to heal itself. Osteopaths typically center their treatment on the musculoskeletal system, the muscles and bones, often using techniques such as bone manipulation and a form of massage.
The Family Physician
A family physician is a doctor—either an MD or a DO—who has been trained to prevent, diagnose, and treat medical conditions in people of all ages. The family physician takes care of the general health of the patient and his entire family. Their training is not limited to internal medicine, but includes some training in psychiatry, obstetrics, gynecology, and surgery. These are the “Marcus Welby” doctors, seemingly able to handle almost any general problem.
There is a separate board certification examination specifically for family practitioners. This is known as the family practice boards. Specializing in family practice medicine requires an additional three years’ training beyond medical school. The amount of exposure to, and degree of expertise in liver disease varies among family practitioners. However, family physicians have not undergone additional specialized training in liver disease.
The Internist
An internist is a doctor—an MD or a DO—who is trained to prevent, diagnose, and treat medical conditions in adolescents and adults, including the elderly. Internists have received some basic training in subspecialty areas of internal medicine, including gastroenterology, hepatology, and infectious diseases. Internists are trained to treat both straightforward and complex problems of the internal organs. They are also trained in emergency medicine and critical care medicine. There is a separate board certification examination specifically for internists. It is known as the internal medicine boards. Specializing in internal medicine requires an additional three years’ training beyond medical school.
The amount of exposure to, and degree of expertise in liver disease varies among internists. Internists have the option of continuing their training in a subspecialty of internal medicine. This requires applying for, and being accepted into, a fellowship in the subspecialty of their choice. gastroenterology, hepatology, and infectious diseases are among the many subspecialties of internal medicine.
The Gastroenterologist
A gastroenterologist is an internist who has completed specialty training in the treatment of digestive disorders. Digestive disorders include disorders of the esophagus, stomach, small and large intestines, pancreas, gallbladder, and liver. In order to become board certified in gastroenterology, the doctor must first become board certified in internal medicine. In order to become eligible to even take the examination for board certification in gastroenterology, a gastrointestinal (GI) fellowship lasting an additional two to three years beyond an internal medicine residency must be completed.
During the course of their two to three years of training in gastroenterology, some gastroenterologists have little exposure to patients with liver disease. On the other hand, some gastroenterologists have a great deal of exposure to patients with liver disease during the course of their gastroenterology specialty training. Thus, the level of experience and expertise among gastroenterologists in diagnosing and treating liver disease varies greatly. It is important for the patient to determine the gastroenterologist’s level of expertise in liver disease prior to establishing a long-term medical relationship with this type of doctor.
The Hepatologist
A hepatologist is the most experienced and qualified type of doctor to treat people with liver disease. Since there is currently no separate board certification examination in the field of hepatology, there is no official definition of a hepatologist. However, there are specialized training programs for doctors who are focused solely on liver disease. These are known as hepatology fellowships and typically last from one to two years. Over the course of a hepatology fellowship, a doctor receives comprehensive training in the diagnosis and treatment of liver disease. This specialty training typically includes extensive exposure to all liver diseases, including those that are rare and infrequently seen. This intense training in liver disease is rarely matched in a gastroenterology fellowship.
A physician who successfully completes a hepatology fellowship is considered a hepatologist. Most hepatologists, although not all, are also gastroenterologists. These doctors have successfully completed both a hepatology and a gastroenterology fellowship. Occasionally, gastroenterologists who have not completed a fellowship in hepatology nonetheless focus their medical practice primarily on the diagnosis and treatment of people with liver disease. While these physicians do not have a separate diploma in the field of liver disease, they may also be considered hepatologists.
For many reasons, it is to the patient’s advantage to choose a hepatologist to treat his liver disease. The patient can be virtually assured that the hepatologist will have substantial experience in the diagnosis and treatment of the full range of liver diseases. Furthermore, hepatologists are likely to be the first to learn about the most up-to-date therapies—both FDA-approved and experimental—and to incorporate them into their practices. However, whether someone chooses to see a gastroenterologist or a hepatologist, it is important to find a doctor who is willing to work with him as an equal partner in the healing process.
Infectious Disease Specialists
An infectious disease specialist is an internist who has completed a specialty fellowship in infectious diseases of all types. Many infectious disease specialists treat people with liver disease caused by infectious - such as hepatitis B and C (both of which are caused by viruses). During the course of their two years of training in infectious diseases, some infectious disease specialists have little exposure to patients with viral hepatitis. On the other hand, some infectious disease specialists receive a great deal of exposure to patients with viral hepatitis during the course of their specialty training. Thus, the level of expertise among infectious disease specialists in diagnosing and treating viral hepatitis varies greatly. It is important for the patient to determine the infectious disease specialist’s level of expertise in treating hepatitis B or C prior to establishing a long-term medical relationship with this type of doctor. It should be stressed that infectious disease doctors have no special expertise treating liver diseases that are not caused by infections – such as alcoholic liver disease or autoimmune hepatitis.
Academic Physicians Versus Private Practitioners
People searching for a doctor should be aware of the differences between academic physicians and private practitioners. Each type of doctor has pros and cons that must be carefully weighed by the patient as part of the process of choosing a physician.
The Academic Physician
An academic physician is a doctor who has accepted a faculty position on staff at a hospital. Often, though not always, the hospital will be associated with a medical school. These doctors spend a portion of their time teaching medical students and physicians-in-training (interns, residents, and fellows) about their specialty—in this case hepatology. Also, some academic physicians spend a considerable percentage of their time conducting research, as opposed to treating patients. Although some of this research is performed in a laboratory, some is within the context of clinical trials involving patients. (See Chapter 11 of my book for a discussion of clinical trials.)
These physicians are usually, but not always, board certified in their specialty, and some have contributed significantly to the advancement of the medical profession in their specialty. However, this is not always the case. Academic physicians carry a title such as assistant professor, associate professor, or professor. This title is based on a number of factors, including, but not limited to, how long they have been practicing in their specialty, their leadership skills, their teaching skills and the contributions made by them in their specialty. No one should ever assume that the qualifications of a given academic physician are superior to those of a given private practitioner merely based on the academic physician’s title or employment by a hospital. This may even hold true of the department chairman.
Academic physicians are generally expected to stay abreast of the newest developments in their field. Such a physician may have initiated or prompted the investigation of a new drug or may have played a significant role in the development of a new medical procedure. Frequently, but not always, academic physicians are involved in conducting investigational trials on the most promising experimental drugs. However, the requirements of entering a study at an academic center may be very rigid and typically involve a risk that the patient will be given a placebo (dummy drug).
Doctors at an academic institution usually allot some time to patient care. However, since these physicians must also teach, the patient will sometimes be evaluated and treated primarily by a doctor-in-training rather than the more experienced faculty member he was expecting. Although these doctor trainees must discuss the patient with the academic physician, the patient will have no assurance of ever meeting with the academic physician, sometimes the patient will only briefly meet with the academic doctor whose credentials prompted his visit in the first place. This may occur on the initial consultation and/or on subsequent visits. Thus, the patient may experience, but cannot count on a close personal relationship with this doctor. Therefore, it is important for a patient making an appointment with a physician who is on staff at a hospital to inquire whether he will be seeing the doctor in a clinic setting or in some type of private office. And, whether he will be seeing the doctor he is requesting the appointment with, opposed to his associates or staff, both for the initial consultation and follow-up visits.
Finally, since academic physicians are typically based within a hospital, their office hours are often limited. Rarely, if ever, will these physicians make themselves available for routine appointments after 5:00 pm, before 8:00 am, or on weekends. And since these doctors have so many other duties in the hospital, such as meetings, teaching, and lecturing, typically only two or three days at most will be devoted to seeing patients, and then only for a limited number of hours. The result of such limited hours is that typically the patient will only be able to book an appointment several weeks, if not months, in advance. Furthermore, hospital-based physicians are typically away from their practice many weeks out of the year attending meetings and lecturing.
The Private Practitioner
A private practitioner is a physician who typically focuses his career on patient care. Usually, but not always, private practitioners take care of people who are admitted to local hospitals in their communities. That is, these private practitioners have either admitting or consulting privileges at one or more local hospitals. Some private practitioners may also be affiliated with an academic institution, where they also treat patients and occasionally teach. And, some private practitioners do not see patients in a hospital setting at all but only in their office for consultations.
Private practitioner physicians may be in solo practice, wherein only one doctor is running the practice; in a partnership, wherein two or more physicians share the responsibilities of the practice; or in a group practice, wherein several doctors are affiliated across an array of different medical specialties. As compared with at an academic setting within a large hospital, a personal relationship with the physician is more likely to develop in a private-practice setting. (Although this is not always the case). If the physician is not a solo practitioner, the patient should inquire whether he will be seen by the same physician on each visit. Similarly, all patients in the process of choosing a physician should inquire whether they will be seen by an actual doctor, as opposed to a nurse or physician’s assistant (P.A.) on each visit.
Private practitioners typically have much longer and more flexible office hours than physicians who are hospital staff members. Thus, early morning, as well as evening, and weekend hours are often available. Of course, the actual hours of availability vary considerably among private practitioners. Also, as compared with hospital-based physicians, private practitioners are less likely to be away from their offices for extended periods of time. Thus, it is possible to obtain an appointment with a highly qualified hepatologist in private practice much more quickly (usually within a few weeks) than with an academic hepatologist of similar stature.
A person doesn’t necessarily have to be treated at an academic institution in order to enroll in a clinical trial of an experimental drug. Some private practitioners conduct clinical studies as part of their practice, in the same manner as would an academic physician. However, this is not especially common and generally applies only to the most knowledgeable privately practicing hepatologists. This is an important area to inquire about prior to making an appointment with the doctor. Typically, studies run in a private practitioner’s office are less rigid in terms of criteria for including or excluding subjects and are less likely to involve the use of a placebo as compared with those conducted at an academic institution. It is important to thoroughly research the credentials of the physician conducting the study, whether the study is conducted in a private practice setting or at an academic institution. This will be discussed in further detail in Chapter 11.
Finally, many people with liver disease incorrectly assume that, if they are treated by an academic physician who is affiliated with a transplant center, this will automatically increase their chances of obtaining a new liver, should one be required. This is a total misconception, as all people are subject to identical rules, regulations, and criteria for liver transplantation—regardless of whether the patient is being treated within an academic or private practice setting. (See chapter xx for more about liver transplantation).
WHAT TO LOOK FOR IN A SPECIALIST
Now that you are familiar with the different kinds of doctors, the next step is to find out about the specialist you have chosen and how he runs his office.
So, what questions should be asked to determine the doctors experience treating people with liver disease?
Determining The Doctor’s Experience With Liver Disease
It is essential to find a doctor who has a significant amount of experience in taking care of people who have liver disease. Information about hepatitis and liver disease rapidly changes. Thus, unless the doctor deals with these diseases multiple times a day it is unlikely that he will be up-to date with information. Even most textbooks are two to three years out-of-date by the time they are published. In this regard, the patient should pose some basic questions to the doctor. See the sample questions that follow. Also, there is no guarantee that the doctor will be totally forthcoming about his level of experience. It’s very important to remember that just because the doctor’s business card or door sign says liver disease, it shouldn’t be assumed that his practice focuses on liver disease. The printer and the sign maker do not verify the doctor’s qualifications and credentials.
- Did your specialty training include a liver fellowship?
As discussed above, a doctor may have trained in the general specialty of gastroenterology, which includes some training in liver disease, or the doctor may have additional training specifically in liver disease. Doctors typically, but not always, hang their diplomas that they are awarded at the completion of their training on the wall. Therefore, simply looking at the doctor’s wall to see if there are two separate diplomas – one for liver disease and the other for gastroenterology will answer this question in many instances.
• ‑Approximately what percentage of your practice is devoted to liver disease, and about how many liver disease patients are you presently treating?
Some doctors have a very large practice but treat very few individuals with liver disease. Other doctors have a relatively small practice, but it may be one that is devoted primarily to taking care of people with liver disease. And some doctors—despite being well known in the field of hepatology—have not actually treated many people with liver disease. These doctors, who often work at large, well-respected hospitals, have devoted their careers to liver disease research rather than patient care.
• Are you involved in liver disease research?
It is advisable to ask the doctor whether he has participated in or is currently conducting research devoted to liver disease. For example, a doctor may be involved in experimental trials to evaluate a promising new form of diet or drug therapy for liver disease or may be involved in evaluating a new method of diagnosing liver disease. A doctor involved in such investigations will afford the patient the opportunity not only to learn firsthand about the most up-to-date therapies, but also may enable the patient to begin using a promising form of therapy before it becomes readily available to the public.
• Have you written any articles on liver disease? Have you written or contributed to any books on liver disease?
A patient should feel free to inquire about the doctor’s medical research experience and also about whether the doctor has authored any publications on liver disease. Many of the most knowledgeable hepatologists have published articles in any well-respected peer-review medical publications, such as Hepatology, Gastro-enterology, or Seminars in Liver Disease. This can be independently checked by accessing medline on the Internet (see Appendix for website address) or by asking for a copy of the article. Doctors are usually more than happy to comply with such a request. Remember, however, that articles appearing in medical publications are written for other physicians and other members of the medical community. These articles will, therefore, contain technical medical terminology. Some doctors have written articles on liver disease for the general public. These may appear in local newspapers, general circulation magazines, specialty publications -such as “Hepatitis” magazine, or publications such as the American Liver Foundation newsletters and pamphlets.
Some of the doctors who are the most dedicated to liver disease have demonstrated their dedication by writing book chapters, book forwards, or entire books on the subject of liver disease – either for the medical or lay community. The patient should feel free to inquire about any of these publications.
• What is your knowledgeability regarding alternatives to conventional medical therapies?
While a liver specialist is primarily involved in prescribing mainstream medical treatments, he should also be knowledgeable about the available alternatives to conventional medical therapy. Extensive evaluation of any alternative treatment is essential before its effectiveness can be assessed. How familiar is the doctor with the alternative therapy in question? How is the doctor basing his recommendations as to the alternative in question? How many of the doctor’s patients tried this alternative treatment, and what were the results?
If a doctor is going to treat your liver disease, it is important that he be knowledgeable as to the most popular alternative treatments for liver disease. While the doctor may not necessarily recommend their usage, it is important that he be conversant with their pros and cons.
- How many people with liver disease have you treated?
It is important to know how experienced the doctor is in treating patients with liver disease. However, while you may be tempted to ask the doctor his age or how long he has been in practice, these questions are of questionable usefulness. Though most people would prefer not to be treated by a doctor who has just completed specialty training, the actual amount of years in practice may not be a reliable indicator of the doctor’s experience with liver disease. For example, a doctor who has been in practice for thirty years may treat only ten individuals with liver disease each week. While another doctor, who may have been in practice for ten years, treats thirty people with liver disease each week. Who is more qualified? The answer is they both may be sufficiently qualified. The bottom line is that the age of the physician and the actual number of years he has been in practice are not reliable criteria by which to judge a doctor’s level of experience.
THE DOCTOR’S OFFICE AND STAFF
In addition to the qualifications of the doctor, there are several important factors which a prospective patient should consider when choosing a liver specialist. It is important to search for a practice in which the doctor has made many amends to make the practice convenient, available and private. This section discusses some additional issues to consider when finding a doctor to treat your liver disease.
Office Staff
Often, the patient can get a baseline impression of the doctor by observing how the office is run. Take note of whether the office staff seems to be knowledgeable about liver disease. A person telephoning the office may not always be able to contact the doctor immediately. Does the doctor have a nurse, medical assistant, or office manager who can promptly and accurately answer questions in the doctor’s absence?
Office Availability
What is the availability of the doctor and the doctor’s staff? How many days a week is the office open? Are the doctor’s hours flexible? Are evening and weekend appointments available? How long must the patient wait to get an appointment? A doctor may not have an appointment available the same day a patient calls, but no matter how busy the doctor’s practice is (even in the busiest of practices), a patient should be able to schedule an appointment within 3 or 4 weeks—at most.
How long does the patient have to wait once in the doctor’s office? If on every visit, the patient is left waiting for more than two hours in the waiting room, then there is something wrong with the doctor’s method of scheduling. But a long wait on occasion should not be cause for concern. Emergencies sometimes arise and can result in delays.
Office Privacy
It is important to be treated by a medical practice that respects your privacy. In fact, it’s the law. Is the nurse’s and office reception area enclosed with a window or door, or is it open thereby allowing patients’ names and personal information to be overheard? Do the doctor or his staff discuss other patients’ information (i.e. on the phone) while in your presence? Can you rely on the doctor and his staff to take the necessary steps to protect your medical information? Is the doctor’s practice in compliance with the Health Insurance Portability and Accountability Act of 1996 (HIPAA)?
What is HIPAA?
HIPAA was developed by the Department of Health and Human Services (HHS). This law applies uniformly to all areas of the United States effective as of April 15, 2003. These laws are a national standard. No doctor’s office or hospital in any area of the country is exempt from this law. The HIPAA law is designed to protect the security and confidentiality of patients’ protected health information (PHI) whether it is on paper, in computers or communicated orally. PHI is any information that the doctor’s office possesses about the patient that identifies the patient and relates to their past, current and future physical and/or mental health condition and the health care products and services that have been provided. Under this law your medical records and conversations with the doctor and doctor’s staff are not readily available to anyone without your written authorization.
All doctors’ offices must provide written notice to their patients describing their rights under this law. Patients typically will be asked to sign, initial or otherwise acknowledge that they received this notice. Furthermore, a notice must also be posted in the doctors’ office describing the basic features of this law. An office which does not display a HIPAA notice is in violation of their patients’ privacy rights and is subject to both civil and criminal penalties. The same applies to an office that does not provide you with a written notice describing your rights under HIPAA.
Office Services
People with liver disease generally need frequent assessment of their blood work. Therefore, it is important to find out whether blood will be drawn at the doctor’s office or whether the patient will be sent to a laboratory to have blood drawn. Obviously, it is a great convenience to have blood drawn in the doctor’s office at the time of the visit.
Often the patient with liver disease will need evaluation of his digestive system for a variety of reasons. The evaluation will typically include an upper endoscopy and a colonoscopy. An upper endoscopy is a flexible tube with a light at the end and is performed to evaluate the esophagus for possible esophageal varices, and the stomach for possible ulcers or infection. A colonoscopy is a flexible tube with a light at the end of it performed to evaluate the lower intestines (colon), for polyps or rectal bleeding, for example. Some doctors perform these tests in the comfort, privacy, and convenience of their office. Other doctors perform these tests at the local hospital, which is invariably more time consuming for the patient, as well as less convenient.
Who Will The Patient Actually Be Seeing?
It is crucial for the patient to find out whether he will be seeing the doctor on the initial, as well as subsequent visits, or a nurse, physician’s assistant (P.A.), or medical assistant (M.A.). You want to know who is actually going to be treating you. For many doctors, their standard procedure is to only conduct the initial evaluation of the patient. All subsequent visits, phone calls or other contacts with the patient are handled by a doctor’s representative – i.e. nurse, medical assistant, or physician assistant. These doctors’ helpers are commonly referred to as “physician extenders”. In such practices, the doctor is directly involved with the patient’s care only in the event of a serious complication. Baring a serious complication, the management of the patient is mostly left in the hands of the physician extender. However, in many practices, every patient is managed personally by the doctor. In such practices, the doctor himself will perform all examinations of the patient, (both initial and subsequent), will personally evaluate the patient’s response to therapy, and will personally make all treatment decisions - both major and minor. In this type of practice, the physician that you have chosen - after researching his level of expertise and experience in liver disease, will be the individual who is treating you.
Finally, find out how many doctors there are in the practice and whether you will be seeing the same doctor at each visit. It is in the best interest of the patient to establish a relationship with one doctor. This way, the doctor’s familiarity with the patient’s medical history and special needs will be maximized. This is likely to lead to the highest rate of success in treatment of the patient’s liver disease.
THE WAYS DOCTORS HELP PATIENTS OUTSIDE THEIR PRACTICES
Treating each person individually is the standard way a doctor helps patients get better. But there are additional ways that a doctor can help people—ways in which he can reach out to large groups of people with liver disease and to their loved ones all at once.
If a doctor spends his spare time involved in activities relating to liver disease, such as writing articles, lecturing, making radio or television appearances, creating instructional videos, or running a website devoted to liver disease, it’s pretty obvious that this doctor is dedicating his career, as well as his free time and spare energy, to helping people with liver disease. Patients should not hesitate to ask their doctors if they are involved in any of these worthy activities.
Publications
A doctor who writes articles on liver disease can reach a large number of people. The article can be contributed to a local newspaper, a health-related magazine, or the newsletter or brochure of a support group or a nonprofit organization devoted to liver disease, such as the American Liver Foundation (ALF) or Hepatitis Foundation International (HFI). Similarly, many pharmaceutical companies involved in the treatment of liver disease have literature concerning the disease and its treatment. The patient should find out if the doctor has contributed to any of these publications. Doctors who have had articles published will often have copies available at their offices that the patient can take home to read.
Lecturing
Does the doctor give lectures on liver disease, either within the local community or nationally? Lectures are regularly sponsored by nonprofit organizations such as ALF or HFI. The general public is normally invited to attend these lectures, either free of charge or for a very minimal fee. A knowledgeable doctor should be able to inform the patient of the date and location of scheduled lectures in the community or nearby areas. The patient should find out if the doctor is invited to speak at these lectures. A doctor who is involved in lecturing to the public will gladly tell the patient when the next lecture is scheduled, so that the patient may attend if he wishes. Or the doctor will describe to the patient the most recent lecture that he has given.
Media Appearances
The media is a means by which the doctor can reach out to many people with liver disease and their loved ones all at the same time. By communicating to the public through the media, the doctor is able to spread information about liver disease to thousands, if not millions, of people. Health topics are frequently discussed on news programs and talk shows. Often, local or cable television stations devote entire programs to liver disease, and radio programs often have short segments related to health topics. The patient should find out if the doctor has appeared on television or radio shows concerning liver disease, or if the doctor has participated in the production of any videotapes devoted to liver disease. A doctor who has appeared on television, radio, or videotape will probably be able to provide the patient with a taped copy of the show, or at the very least, provide information about how to obtain a copy.
Internet Websites
There are numerous liver-related websites on the Internet. The patient should find out if the doctor is involved in running one of these websites. The doctor should be able to direct the patient to some informative, accurate Internet websites related to liver disease. This topic will be discussed in more detail later in this chapter on page xx.
Associations and Foundations
Methods for the diagnosis and treatment of liver disease change rapidly on an ongoing basis. It is important to be treated by a doctor who is familiar with the most up-to-date developments. There are many professional organizations that keep doctors abreast of the most recent information on liver disease. The most prominent of these organizations in the field of liver disease is the American Association for the Study of Liver Disease (AASLD). A doctor who has been elected to membership in the AASLD is most likely to be actively involved in liver disease. The AASLD is an association of physicians and scientists who are dedicated to the advancement and application of knowledge of liver disease.
There are also numerous lay (non-professional) organizations that are dedicated to increasing the awareness of liver disease. Perhaps the best-known of these is the American Liver Foundation (ALF) is a voluntary nonprofit organization whose membership consists of doctors, patients, and any other individuals interested in liver disease. ALF’s major goals include educating the public about liver disease and fostering the prevention and treatment of liver disease. A doctor may be involved with ALF to varying degrees, ranging from being a member to running a support group to lecturing to the public on a topic pertaining to liver disease. Doctors who have demonstrated exceptional dedication to the cause of helping individuals with liver disease are often invited to serve as a board member of ALF, either at the national or local level. A patient can contact ALF to inquire about a doctor’s level of activity in this organization.
INSURANCE AND HMO PLANS
A full discussion of insurance plans, including HMOs, POSs and PPOs, is beyond the scope of this book. However, the patient should be aware of one very important point concerning insurance plans, which is described in the following scenario: After Tom’s exhausting search, he finally found a specialist that he wanted to consult with. However, when he checked in his insurance book, to his great disappointment, the specialist’s name was nowhere to be found! Now what?
All patients should be aware that most insurance plans will pay for a visit to a doctor who is not included in their plan, if—and this is an important if—the doctor offers special or unique services that no other doctor in the plan offers. For example, some liver specialists offer a wealth of experience treating people with liver disease, which greatly exceeds that of any other doctors who are currently listed on the plan, or they are offering treatment options that are not available through any of the other doctors on the plan. In these circumstances, an appeal letter or even a phone call to the appropriate insurance company representative explaining the dilemma often results in the patient being granted coverage for a consultation with the desired specialist. Also, the patient may want to ask the doctor personally if he would consider joining his health plan.
LIVER DISEASE SPECIALISTS AND THE INTERNET
The Internet may be considered a double-edged sword when it comes to liver disease. It is an ocean of both information and misinformation. Surf with caution. The number of Internet websites continues to grow at an explosive rate. Despite the relative newness of the Internet, there are already over one hundred Internet websites devoted to liver disease and hepatitis. It can be difficult for the layperson to determine which information is correct and which information is not. It is most important for the patient using the Internet to determine who is sponsoring the website.
Is a pharmaceutical company maintaining the website? For example, Schering-Plough, Roche, and Intermune, three major drug companies that manufacture and distribute pharmaceuticals used in the prevention or treatment of liver disease all maintain Internet websites. Each of these websites contains useful information, but, keep in mind that these companies also are promoting their product. Is it a well-respected hepatologist who maintains the website? For example, I maintain a regularly updated Internet website, and there are a number of other excellent hepatologists who also maintain websites devoted to liver disease. Or, is it a health-care professional who is not a hepatologist? Does a well-established not-for-profit organization maintain the website? For example, ALF and HFI, in addition to many other groups maintain helpful websites. Is it a knowledgeable patient eager to help others who maintains the site? Or is it a not-so-knowledgeable patient who is giving false and possibly dangerous information? Be careful. (See Appendix for some helpful website addresses.)
Some websites provide referrals to doctors who purportedly specialize in liver disease. Unfortunately, it is often impossible to ascertain what criteria were used in selecting the referred doctors. Some sites merely require a doctor to pay a fee in order to be listed. While it may be difficult to obtain accurate information from searching the Internet, one generality may be relied on: If the doctor has a website devoted to liver disease, it is likely his practice is focused on taking care of people with liver disease.
CONSULTING WITH THE SPECIALIST
Now that the patient has located a specialist, there are a few tips to follow, which will help make the appointment as smooth and efficient as possible for both the patient and the doctor. It is normal to be nervous about seeing a specialist. So much new and crucial information will be provided to the patient during this visit. It is to be expected that after the initial consultation is over, the patient will not recall a significant amount of what the doctor has said. For this reason, the patient should try to have a relative or close friend along for the consultation. Prior to the visit, the patient should make a list of all of the questions that he wants answered during this visit. The patient should bring this list to the consultation and should not leave the doctor’s office until every question has been satisfactorily answered. It’s perfectly okay to take short notes while the doctor is talking and to check off each question after the doctor has answered it. If necessary, the patient should request that the doctor write down unfamiliar technical medical terms used during the conversation.
The patient can make the initial consultation more productive for the specialist by bringing all prior records from other doctors to the visit. This will better enable the doctor to promptly and accurately assess the patient’s condition on the initial visit. It is especially important to bring the doctor copies of all previously performed blood work, imaging studies, and liver biopsy reports or slides. Doing so will not only assist the doctor, but it can sometimes eliminate the necessity of repeating the tests and/or biopsy.
Remember, all prior records, reports, and slides legally belong to the patient. These records should never be difficult for the patient to obtain. However, most doctors’ offices, hospitals, and medical facilities require a written request authorizing the release of the records to another doctor or hospital. Often there is a fee. Be aware that the maximum fee that by law can be charged for medical records is seventy-five cents per page.
Finally, the patient should always bring the doctor a list of all medications, including over-the-counter medications, vitamins, dietary supplements, and/or herbal remedies, that he is taking. The more comprehensive the information the patient provides, the more accurate the specialist’s advice will be.
FINDING SECOND OPINIONS
If a patient is not comfortable with the advice he receives from a specialist, it is advisable to seek another opinion. Always make sure that a second opinion is provided by a doctor whose knowledge of liver disease is superior to, or at least equal to, that of the first specialist. However, patients should keep multiple opinions in perspective. Under no circumstances should patients ever make it their objective to shop around for opinions until they hear the diagnosis or prognosis that they are looking for. A game plan of this nature could only cause a serious illness to be left neglected, untreated, or treated inappropriately. It is natural for anyone to hope to hear that there is nothing wrong and that a liver biopsy and treatment aren’t necessary. In some cases, these statements may in fact be accurate; however, if the patient has seen two or three well-respected liver specialists, all of whom concur that something is wrong, the patient must accept that he has a chronic illness that may require treatment.
Source
Melissa Palmer, MD is the author of " Dr. Melissa Palmer's Guide of Hepatitis and Liver Disease". (Published 2004. Penguin Putnam).
There are many different kinds of doctors who evaluate and treat people with liver disorders. First, there is the family physician or internist. These doctors are also referred to as primary care physicians (PCPs). They are often the first ones to discover that something is wrong with the liver. From there, the patient is customarily referred to a specialist—either a gastroenterologist, hepatologist, or infectious disease specialist—for further evaluation and treatment. This specialist may be in a practice located at an academic institution or in a private practice located in a community setting. The difference between the various types of doctors a patient with liver disease encounters may sometimes be confusing. Hopefully, this section will clarify these differences in order to eliminate any future confusion.
The Medical Doctor (MD)
Medical Doctors (MDs) are physicians who have successfully completed four years of medical school training. After graduating from medical school, these doctors must complete a minimum of one additional year of training in a hospital in what is known as an internship. They must then pass a state-licensing exam in order to practice medicine in that state. After obtaining their license, they have the right to practice medicine in that state. However, many doctors choose to continue their training in a hospital by undergoing a residency—typically an additional two years.
After completing their residency, these doctors must take an exam in order to become board certified in a specialty, such as family medicine or internal medicine. Doctors may practice medicine whether or not they pass this exam. Doctors who become family doctors or internists have general knowledge in all areas of medicine including the heart, lungs, kidneys, stomach, intestines, and liver. At this time, a doctor may decide to undergo additional specialty training, known as a fellowship, in a specific area of internal medicine, such as gastroenterology, hepatology, or infectious diseases, in order to become an expert in these areas.
The Doctor of Osteopathy (DO)
Doctors of osteopathy (DOs) are commonly referred to as osteopaths. These are doctors who graduated from a four-year osteopathic school. They must also complete a one-year internship in a hospital in order to be eligible to obtain a license to practice medicine. Osteopaths can also choose to undergo an additional two-year residency, and may thereafter undergo specialty training in a specific area of medicine.
Osteopaths tend to focus on treating “the body as a whole,” particularly on the body’s ability to heal itself. Osteopaths typically center their treatment on the musculoskeletal system, the muscles and bones, often using techniques such as bone manipulation and a form of massage.
The Family Physician
A family physician is a doctor—either an MD or a DO—who has been trained to prevent, diagnose, and treat medical conditions in people of all ages. The family physician takes care of the general health of the patient and his entire family. Their training is not limited to internal medicine, but includes some training in psychiatry, obstetrics, gynecology, and surgery. These are the “Marcus Welby” doctors, seemingly able to handle almost any general problem.
There is a separate board certification examination specifically for family practitioners. This is known as the family practice boards. Specializing in family practice medicine requires an additional three years’ training beyond medical school. The amount of exposure to, and degree of expertise in liver disease varies among family practitioners. However, family physicians have not undergone additional specialized training in liver disease.
The Internist
An internist is a doctor—an MD or a DO—who is trained to prevent, diagnose, and treat medical conditions in adolescents and adults, including the elderly. Internists have received some basic training in subspecialty areas of internal medicine, including gastroenterology, hepatology, and infectious diseases. Internists are trained to treat both straightforward and complex problems of the internal organs. They are also trained in emergency medicine and critical care medicine. There is a separate board certification examination specifically for internists. It is known as the internal medicine boards. Specializing in internal medicine requires an additional three years’ training beyond medical school.
The amount of exposure to, and degree of expertise in liver disease varies among internists. Internists have the option of continuing their training in a subspecialty of internal medicine. This requires applying for, and being accepted into, a fellowship in the subspecialty of their choice. gastroenterology, hepatology, and infectious diseases are among the many subspecialties of internal medicine.
The Gastroenterologist
A gastroenterologist is an internist who has completed specialty training in the treatment of digestive disorders. Digestive disorders include disorders of the esophagus, stomach, small and large intestines, pancreas, gallbladder, and liver. In order to become board certified in gastroenterology, the doctor must first become board certified in internal medicine. In order to become eligible to even take the examination for board certification in gastroenterology, a gastrointestinal (GI) fellowship lasting an additional two to three years beyond an internal medicine residency must be completed.
During the course of their two to three years of training in gastroenterology, some gastroenterologists have little exposure to patients with liver disease. On the other hand, some gastroenterologists have a great deal of exposure to patients with liver disease during the course of their gastroenterology specialty training. Thus, the level of experience and expertise among gastroenterologists in diagnosing and treating liver disease varies greatly. It is important for the patient to determine the gastroenterologist’s level of expertise in liver disease prior to establishing a long-term medical relationship with this type of doctor.
The Hepatologist
A hepatologist is the most experienced and qualified type of doctor to treat people with liver disease. Since there is currently no separate board certification examination in the field of hepatology, there is no official definition of a hepatologist. However, there are specialized training programs for doctors who are focused solely on liver disease. These are known as hepatology fellowships and typically last from one to two years. Over the course of a hepatology fellowship, a doctor receives comprehensive training in the diagnosis and treatment of liver disease. This specialty training typically includes extensive exposure to all liver diseases, including those that are rare and infrequently seen. This intense training in liver disease is rarely matched in a gastroenterology fellowship.
A physician who successfully completes a hepatology fellowship is considered a hepatologist. Most hepatologists, although not all, are also gastroenterologists. These doctors have successfully completed both a hepatology and a gastroenterology fellowship. Occasionally, gastroenterologists who have not completed a fellowship in hepatology nonetheless focus their medical practice primarily on the diagnosis and treatment of people with liver disease. While these physicians do not have a separate diploma in the field of liver disease, they may also be considered hepatologists.
For many reasons, it is to the patient’s advantage to choose a hepatologist to treat his liver disease. The patient can be virtually assured that the hepatologist will have substantial experience in the diagnosis and treatment of the full range of liver diseases. Furthermore, hepatologists are likely to be the first to learn about the most up-to-date therapies—both FDA-approved and experimental—and to incorporate them into their practices. However, whether someone chooses to see a gastroenterologist or a hepatologist, it is important to find a doctor who is willing to work with him as an equal partner in the healing process.
Infectious Disease Specialists
An infectious disease specialist is an internist who has completed a specialty fellowship in infectious diseases of all types. Many infectious disease specialists treat people with liver disease caused by infectious - such as hepatitis B and C (both of which are caused by viruses). During the course of their two years of training in infectious diseases, some infectious disease specialists have little exposure to patients with viral hepatitis. On the other hand, some infectious disease specialists receive a great deal of exposure to patients with viral hepatitis during the course of their specialty training. Thus, the level of expertise among infectious disease specialists in diagnosing and treating viral hepatitis varies greatly. It is important for the patient to determine the infectious disease specialist’s level of expertise in treating hepatitis B or C prior to establishing a long-term medical relationship with this type of doctor. It should be stressed that infectious disease doctors have no special expertise treating liver diseases that are not caused by infections – such as alcoholic liver disease or autoimmune hepatitis.
Academic Physicians Versus Private Practitioners
People searching for a doctor should be aware of the differences between academic physicians and private practitioners. Each type of doctor has pros and cons that must be carefully weighed by the patient as part of the process of choosing a physician.
The Academic Physician
An academic physician is a doctor who has accepted a faculty position on staff at a hospital. Often, though not always, the hospital will be associated with a medical school. These doctors spend a portion of their time teaching medical students and physicians-in-training (interns, residents, and fellows) about their specialty—in this case hepatology. Also, some academic physicians spend a considerable percentage of their time conducting research, as opposed to treating patients. Although some of this research is performed in a laboratory, some is within the context of clinical trials involving patients. (See Chapter 11 of my book for a discussion of clinical trials.)
These physicians are usually, but not always, board certified in their specialty, and some have contributed significantly to the advancement of the medical profession in their specialty. However, this is not always the case. Academic physicians carry a title such as assistant professor, associate professor, or professor. This title is based on a number of factors, including, but not limited to, how long they have been practicing in their specialty, their leadership skills, their teaching skills and the contributions made by them in their specialty. No one should ever assume that the qualifications of a given academic physician are superior to those of a given private practitioner merely based on the academic physician’s title or employment by a hospital. This may even hold true of the department chairman.
Academic physicians are generally expected to stay abreast of the newest developments in their field. Such a physician may have initiated or prompted the investigation of a new drug or may have played a significant role in the development of a new medical procedure. Frequently, but not always, academic physicians are involved in conducting investigational trials on the most promising experimental drugs. However, the requirements of entering a study at an academic center may be very rigid and typically involve a risk that the patient will be given a placebo (dummy drug).
Doctors at an academic institution usually allot some time to patient care. However, since these physicians must also teach, the patient will sometimes be evaluated and treated primarily by a doctor-in-training rather than the more experienced faculty member he was expecting. Although these doctor trainees must discuss the patient with the academic physician, the patient will have no assurance of ever meeting with the academic physician, sometimes the patient will only briefly meet with the academic doctor whose credentials prompted his visit in the first place. This may occur on the initial consultation and/or on subsequent visits. Thus, the patient may experience, but cannot count on a close personal relationship with this doctor. Therefore, it is important for a patient making an appointment with a physician who is on staff at a hospital to inquire whether he will be seeing the doctor in a clinic setting or in some type of private office. And, whether he will be seeing the doctor he is requesting the appointment with, opposed to his associates or staff, both for the initial consultation and follow-up visits.
Finally, since academic physicians are typically based within a hospital, their office hours are often limited. Rarely, if ever, will these physicians make themselves available for routine appointments after 5:00 pm, before 8:00 am, or on weekends. And since these doctors have so many other duties in the hospital, such as meetings, teaching, and lecturing, typically only two or three days at most will be devoted to seeing patients, and then only for a limited number of hours. The result of such limited hours is that typically the patient will only be able to book an appointment several weeks, if not months, in advance. Furthermore, hospital-based physicians are typically away from their practice many weeks out of the year attending meetings and lecturing.
The Private Practitioner
A private practitioner is a physician who typically focuses his career on patient care. Usually, but not always, private practitioners take care of people who are admitted to local hospitals in their communities. That is, these private practitioners have either admitting or consulting privileges at one or more local hospitals. Some private practitioners may also be affiliated with an academic institution, where they also treat patients and occasionally teach. And, some private practitioners do not see patients in a hospital setting at all but only in their office for consultations.
Private practitioner physicians may be in solo practice, wherein only one doctor is running the practice; in a partnership, wherein two or more physicians share the responsibilities of the practice; or in a group practice, wherein several doctors are affiliated across an array of different medical specialties. As compared with at an academic setting within a large hospital, a personal relationship with the physician is more likely to develop in a private-practice setting. (Although this is not always the case). If the physician is not a solo practitioner, the patient should inquire whether he will be seen by the same physician on each visit. Similarly, all patients in the process of choosing a physician should inquire whether they will be seen by an actual doctor, as opposed to a nurse or physician’s assistant (P.A.) on each visit.
Private practitioners typically have much longer and more flexible office hours than physicians who are hospital staff members. Thus, early morning, as well as evening, and weekend hours are often available. Of course, the actual hours of availability vary considerably among private practitioners. Also, as compared with hospital-based physicians, private practitioners are less likely to be away from their offices for extended periods of time. Thus, it is possible to obtain an appointment with a highly qualified hepatologist in private practice much more quickly (usually within a few weeks) than with an academic hepatologist of similar stature.
A person doesn’t necessarily have to be treated at an academic institution in order to enroll in a clinical trial of an experimental drug. Some private practitioners conduct clinical studies as part of their practice, in the same manner as would an academic physician. However, this is not especially common and generally applies only to the most knowledgeable privately practicing hepatologists. This is an important area to inquire about prior to making an appointment with the doctor. Typically, studies run in a private practitioner’s office are less rigid in terms of criteria for including or excluding subjects and are less likely to involve the use of a placebo as compared with those conducted at an academic institution. It is important to thoroughly research the credentials of the physician conducting the study, whether the study is conducted in a private practice setting or at an academic institution. This will be discussed in further detail in Chapter 11.
Finally, many people with liver disease incorrectly assume that, if they are treated by an academic physician who is affiliated with a transplant center, this will automatically increase their chances of obtaining a new liver, should one be required. This is a total misconception, as all people are subject to identical rules, regulations, and criteria for liver transplantation—regardless of whether the patient is being treated within an academic or private practice setting. (See chapter xx for more about liver transplantation).
WHAT TO LOOK FOR IN A SPECIALIST
Now that you are familiar with the different kinds of doctors, the next step is to find out about the specialist you have chosen and how he runs his office.
So, what questions should be asked to determine the doctors experience treating people with liver disease?
Determining The Doctor’s Experience With Liver Disease
It is essential to find a doctor who has a significant amount of experience in taking care of people who have liver disease. Information about hepatitis and liver disease rapidly changes. Thus, unless the doctor deals with these diseases multiple times a day it is unlikely that he will be up-to date with information. Even most textbooks are two to three years out-of-date by the time they are published. In this regard, the patient should pose some basic questions to the doctor. See the sample questions that follow. Also, there is no guarantee that the doctor will be totally forthcoming about his level of experience. It’s very important to remember that just because the doctor’s business card or door sign says liver disease, it shouldn’t be assumed that his practice focuses on liver disease. The printer and the sign maker do not verify the doctor’s qualifications and credentials.
- Did your specialty training include a liver fellowship?
As discussed above, a doctor may have trained in the general specialty of gastroenterology, which includes some training in liver disease, or the doctor may have additional training specifically in liver disease. Doctors typically, but not always, hang their diplomas that they are awarded at the completion of their training on the wall. Therefore, simply looking at the doctor’s wall to see if there are two separate diplomas – one for liver disease and the other for gastroenterology will answer this question in many instances.
• ‑Approximately what percentage of your practice is devoted to liver disease, and about how many liver disease patients are you presently treating?
Some doctors have a very large practice but treat very few individuals with liver disease. Other doctors have a relatively small practice, but it may be one that is devoted primarily to taking care of people with liver disease. And some doctors—despite being well known in the field of hepatology—have not actually treated many people with liver disease. These doctors, who often work at large, well-respected hospitals, have devoted their careers to liver disease research rather than patient care.
• Are you involved in liver disease research?
It is advisable to ask the doctor whether he has participated in or is currently conducting research devoted to liver disease. For example, a doctor may be involved in experimental trials to evaluate a promising new form of diet or drug therapy for liver disease or may be involved in evaluating a new method of diagnosing liver disease. A doctor involved in such investigations will afford the patient the opportunity not only to learn firsthand about the most up-to-date therapies, but also may enable the patient to begin using a promising form of therapy before it becomes readily available to the public.
• Have you written any articles on liver disease? Have you written or contributed to any books on liver disease?
A patient should feel free to inquire about the doctor’s medical research experience and also about whether the doctor has authored any publications on liver disease. Many of the most knowledgeable hepatologists have published articles in any well-respected peer-review medical publications, such as Hepatology, Gastro-enterology, or Seminars in Liver Disease. This can be independently checked by accessing medline on the Internet (see Appendix for website address) or by asking for a copy of the article. Doctors are usually more than happy to comply with such a request. Remember, however, that articles appearing in medical publications are written for other physicians and other members of the medical community. These articles will, therefore, contain technical medical terminology. Some doctors have written articles on liver disease for the general public. These may appear in local newspapers, general circulation magazines, specialty publications -such as “Hepatitis” magazine, or publications such as the American Liver Foundation newsletters and pamphlets.
Some of the doctors who are the most dedicated to liver disease have demonstrated their dedication by writing book chapters, book forwards, or entire books on the subject of liver disease – either for the medical or lay community. The patient should feel free to inquire about any of these publications.
• What is your knowledgeability regarding alternatives to conventional medical therapies?
While a liver specialist is primarily involved in prescribing mainstream medical treatments, he should also be knowledgeable about the available alternatives to conventional medical therapy. Extensive evaluation of any alternative treatment is essential before its effectiveness can be assessed. How familiar is the doctor with the alternative therapy in question? How is the doctor basing his recommendations as to the alternative in question? How many of the doctor’s patients tried this alternative treatment, and what were the results?
If a doctor is going to treat your liver disease, it is important that he be knowledgeable as to the most popular alternative treatments for liver disease. While the doctor may not necessarily recommend their usage, it is important that he be conversant with their pros and cons.
- How many people with liver disease have you treated?
It is important to know how experienced the doctor is in treating patients with liver disease. However, while you may be tempted to ask the doctor his age or how long he has been in practice, these questions are of questionable usefulness. Though most people would prefer not to be treated by a doctor who has just completed specialty training, the actual amount of years in practice may not be a reliable indicator of the doctor’s experience with liver disease. For example, a doctor who has been in practice for thirty years may treat only ten individuals with liver disease each week. While another doctor, who may have been in practice for ten years, treats thirty people with liver disease each week. Who is more qualified? The answer is they both may be sufficiently qualified. The bottom line is that the age of the physician and the actual number of years he has been in practice are not reliable criteria by which to judge a doctor’s level of experience.
THE DOCTOR’S OFFICE AND STAFF
In addition to the qualifications of the doctor, there are several important factors which a prospective patient should consider when choosing a liver specialist. It is important to search for a practice in which the doctor has made many amends to make the practice convenient, available and private. This section discusses some additional issues to consider when finding a doctor to treat your liver disease.
Office Staff
Often, the patient can get a baseline impression of the doctor by observing how the office is run. Take note of whether the office staff seems to be knowledgeable about liver disease. A person telephoning the office may not always be able to contact the doctor immediately. Does the doctor have a nurse, medical assistant, or office manager who can promptly and accurately answer questions in the doctor’s absence?
Office Availability
What is the availability of the doctor and the doctor’s staff? How many days a week is the office open? Are the doctor’s hours flexible? Are evening and weekend appointments available? How long must the patient wait to get an appointment? A doctor may not have an appointment available the same day a patient calls, but no matter how busy the doctor’s practice is (even in the busiest of practices), a patient should be able to schedule an appointment within 3 or 4 weeks—at most.
How long does the patient have to wait once in the doctor’s office? If on every visit, the patient is left waiting for more than two hours in the waiting room, then there is something wrong with the doctor’s method of scheduling. But a long wait on occasion should not be cause for concern. Emergencies sometimes arise and can result in delays.
Office Privacy
It is important to be treated by a medical practice that respects your privacy. In fact, it’s the law. Is the nurse’s and office reception area enclosed with a window or door, or is it open thereby allowing patients’ names and personal information to be overheard? Do the doctor or his staff discuss other patients’ information (i.e. on the phone) while in your presence? Can you rely on the doctor and his staff to take the necessary steps to protect your medical information? Is the doctor’s practice in compliance with the Health Insurance Portability and Accountability Act of 1996 (HIPAA)?
What is HIPAA?
HIPAA was developed by the Department of Health and Human Services (HHS). This law applies uniformly to all areas of the United States effective as of April 15, 2003. These laws are a national standard. No doctor’s office or hospital in any area of the country is exempt from this law. The HIPAA law is designed to protect the security and confidentiality of patients’ protected health information (PHI) whether it is on paper, in computers or communicated orally. PHI is any information that the doctor’s office possesses about the patient that identifies the patient and relates to their past, current and future physical and/or mental health condition and the health care products and services that have been provided. Under this law your medical records and conversations with the doctor and doctor’s staff are not readily available to anyone without your written authorization.
All doctors’ offices must provide written notice to their patients describing their rights under this law. Patients typically will be asked to sign, initial or otherwise acknowledge that they received this notice. Furthermore, a notice must also be posted in the doctors’ office describing the basic features of this law. An office which does not display a HIPAA notice is in violation of their patients’ privacy rights and is subject to both civil and criminal penalties. The same applies to an office that does not provide you with a written notice describing your rights under HIPAA.
Office Services
People with liver disease generally need frequent assessment of their blood work. Therefore, it is important to find out whether blood will be drawn at the doctor’s office or whether the patient will be sent to a laboratory to have blood drawn. Obviously, it is a great convenience to have blood drawn in the doctor’s office at the time of the visit.
Often the patient with liver disease will need evaluation of his digestive system for a variety of reasons. The evaluation will typically include an upper endoscopy and a colonoscopy. An upper endoscopy is a flexible tube with a light at the end and is performed to evaluate the esophagus for possible esophageal varices, and the stomach for possible ulcers or infection. A colonoscopy is a flexible tube with a light at the end of it performed to evaluate the lower intestines (colon), for polyps or rectal bleeding, for example. Some doctors perform these tests in the comfort, privacy, and convenience of their office. Other doctors perform these tests at the local hospital, which is invariably more time consuming for the patient, as well as less convenient.
Who Will The Patient Actually Be Seeing?
It is crucial for the patient to find out whether he will be seeing the doctor on the initial, as well as subsequent visits, or a nurse, physician’s assistant (P.A.), or medical assistant (M.A.). You want to know who is actually going to be treating you. For many doctors, their standard procedure is to only conduct the initial evaluation of the patient. All subsequent visits, phone calls or other contacts with the patient are handled by a doctor’s representative – i.e. nurse, medical assistant, or physician assistant. These doctors’ helpers are commonly referred to as “physician extenders”. In such practices, the doctor is directly involved with the patient’s care only in the event of a serious complication. Baring a serious complication, the management of the patient is mostly left in the hands of the physician extender. However, in many practices, every patient is managed personally by the doctor. In such practices, the doctor himself will perform all examinations of the patient, (both initial and subsequent), will personally evaluate the patient’s response to therapy, and will personally make all treatment decisions - both major and minor. In this type of practice, the physician that you have chosen - after researching his level of expertise and experience in liver disease, will be the individual who is treating you.
Finally, find out how many doctors there are in the practice and whether you will be seeing the same doctor at each visit. It is in the best interest of the patient to establish a relationship with one doctor. This way, the doctor’s familiarity with the patient’s medical history and special needs will be maximized. This is likely to lead to the highest rate of success in treatment of the patient’s liver disease.
THE WAYS DOCTORS HELP PATIENTS OUTSIDE THEIR PRACTICES
Treating each person individually is the standard way a doctor helps patients get better. But there are additional ways that a doctor can help people—ways in which he can reach out to large groups of people with liver disease and to their loved ones all at once.
If a doctor spends his spare time involved in activities relating to liver disease, such as writing articles, lecturing, making radio or television appearances, creating instructional videos, or running a website devoted to liver disease, it’s pretty obvious that this doctor is dedicating his career, as well as his free time and spare energy, to helping people with liver disease. Patients should not hesitate to ask their doctors if they are involved in any of these worthy activities.
Publications
A doctor who writes articles on liver disease can reach a large number of people. The article can be contributed to a local newspaper, a health-related magazine, or the newsletter or brochure of a support group or a nonprofit organization devoted to liver disease, such as the American Liver Foundation (ALF) or Hepatitis Foundation International (HFI). Similarly, many pharmaceutical companies involved in the treatment of liver disease have literature concerning the disease and its treatment. The patient should find out if the doctor has contributed to any of these publications. Doctors who have had articles published will often have copies available at their offices that the patient can take home to read.
Lecturing
Does the doctor give lectures on liver disease, either within the local community or nationally? Lectures are regularly sponsored by nonprofit organizations such as ALF or HFI. The general public is normally invited to attend these lectures, either free of charge or for a very minimal fee. A knowledgeable doctor should be able to inform the patient of the date and location of scheduled lectures in the community or nearby areas. The patient should find out if the doctor is invited to speak at these lectures. A doctor who is involved in lecturing to the public will gladly tell the patient when the next lecture is scheduled, so that the patient may attend if he wishes. Or the doctor will describe to the patient the most recent lecture that he has given.
Media Appearances
The media is a means by which the doctor can reach out to many people with liver disease and their loved ones all at the same time. By communicating to the public through the media, the doctor is able to spread information about liver disease to thousands, if not millions, of people. Health topics are frequently discussed on news programs and talk shows. Often, local or cable television stations devote entire programs to liver disease, and radio programs often have short segments related to health topics. The patient should find out if the doctor has appeared on television or radio shows concerning liver disease, or if the doctor has participated in the production of any videotapes devoted to liver disease. A doctor who has appeared on television, radio, or videotape will probably be able to provide the patient with a taped copy of the show, or at the very least, provide information about how to obtain a copy.
Internet Websites
There are numerous liver-related websites on the Internet. The patient should find out if the doctor is involved in running one of these websites. The doctor should be able to direct the patient to some informative, accurate Internet websites related to liver disease. This topic will be discussed in more detail later in this chapter on page xx.
Associations and Foundations
Methods for the diagnosis and treatment of liver disease change rapidly on an ongoing basis. It is important to be treated by a doctor who is familiar with the most up-to-date developments. There are many professional organizations that keep doctors abreast of the most recent information on liver disease. The most prominent of these organizations in the field of liver disease is the American Association for the Study of Liver Disease (AASLD). A doctor who has been elected to membership in the AASLD is most likely to be actively involved in liver disease. The AASLD is an association of physicians and scientists who are dedicated to the advancement and application of knowledge of liver disease.
There are also numerous lay (non-professional) organizations that are dedicated to increasing the awareness of liver disease. Perhaps the best-known of these is the American Liver Foundation (ALF) is a voluntary nonprofit organization whose membership consists of doctors, patients, and any other individuals interested in liver disease. ALF’s major goals include educating the public about liver disease and fostering the prevention and treatment of liver disease. A doctor may be involved with ALF to varying degrees, ranging from being a member to running a support group to lecturing to the public on a topic pertaining to liver disease. Doctors who have demonstrated exceptional dedication to the cause of helping individuals with liver disease are often invited to serve as a board member of ALF, either at the national or local level. A patient can contact ALF to inquire about a doctor’s level of activity in this organization.
INSURANCE AND HMO PLANS
A full discussion of insurance plans, including HMOs, POSs and PPOs, is beyond the scope of this book. However, the patient should be aware of one very important point concerning insurance plans, which is described in the following scenario: After Tom’s exhausting search, he finally found a specialist that he wanted to consult with. However, when he checked in his insurance book, to his great disappointment, the specialist’s name was nowhere to be found! Now what?
All patients should be aware that most insurance plans will pay for a visit to a doctor who is not included in their plan, if—and this is an important if—the doctor offers special or unique services that no other doctor in the plan offers. For example, some liver specialists offer a wealth of experience treating people with liver disease, which greatly exceeds that of any other doctors who are currently listed on the plan, or they are offering treatment options that are not available through any of the other doctors on the plan. In these circumstances, an appeal letter or even a phone call to the appropriate insurance company representative explaining the dilemma often results in the patient being granted coverage for a consultation with the desired specialist. Also, the patient may want to ask the doctor personally if he would consider joining his health plan.
LIVER DISEASE SPECIALISTS AND THE INTERNET
The Internet may be considered a double-edged sword when it comes to liver disease. It is an ocean of both information and misinformation. Surf with caution. The number of Internet websites continues to grow at an explosive rate. Despite the relative newness of the Internet, there are already over one hundred Internet websites devoted to liver disease and hepatitis. It can be difficult for the layperson to determine which information is correct and which information is not. It is most important for the patient using the Internet to determine who is sponsoring the website.
Is a pharmaceutical company maintaining the website? For example, Schering-Plough, Roche, and Intermune, three major drug companies that manufacture and distribute pharmaceuticals used in the prevention or treatment of liver disease all maintain Internet websites. Each of these websites contains useful information, but, keep in mind that these companies also are promoting their product. Is it a well-respected hepatologist who maintains the website? For example, I maintain a regularly updated Internet website, and there are a number of other excellent hepatologists who also maintain websites devoted to liver disease. Or, is it a health-care professional who is not a hepatologist? Does a well-established not-for-profit organization maintain the website? For example, ALF and HFI, in addition to many other groups maintain helpful websites. Is it a knowledgeable patient eager to help others who maintains the site? Or is it a not-so-knowledgeable patient who is giving false and possibly dangerous information? Be careful. (See Appendix for some helpful website addresses.)
Some websites provide referrals to doctors who purportedly specialize in liver disease. Unfortunately, it is often impossible to ascertain what criteria were used in selecting the referred doctors. Some sites merely require a doctor to pay a fee in order to be listed. While it may be difficult to obtain accurate information from searching the Internet, one generality may be relied on: If the doctor has a website devoted to liver disease, it is likely his practice is focused on taking care of people with liver disease.
CONSULTING WITH THE SPECIALIST
Now that the patient has located a specialist, there are a few tips to follow, which will help make the appointment as smooth and efficient as possible for both the patient and the doctor. It is normal to be nervous about seeing a specialist. So much new and crucial information will be provided to the patient during this visit. It is to be expected that after the initial consultation is over, the patient will not recall a significant amount of what the doctor has said. For this reason, the patient should try to have a relative or close friend along for the consultation. Prior to the visit, the patient should make a list of all of the questions that he wants answered during this visit. The patient should bring this list to the consultation and should not leave the doctor’s office until every question has been satisfactorily answered. It’s perfectly okay to take short notes while the doctor is talking and to check off each question after the doctor has answered it. If necessary, the patient should request that the doctor write down unfamiliar technical medical terms used during the conversation.
The patient can make the initial consultation more productive for the specialist by bringing all prior records from other doctors to the visit. This will better enable the doctor to promptly and accurately assess the patient’s condition on the initial visit. It is especially important to bring the doctor copies of all previously performed blood work, imaging studies, and liver biopsy reports or slides. Doing so will not only assist the doctor, but it can sometimes eliminate the necessity of repeating the tests and/or biopsy.
Remember, all prior records, reports, and slides legally belong to the patient. These records should never be difficult for the patient to obtain. However, most doctors’ offices, hospitals, and medical facilities require a written request authorizing the release of the records to another doctor or hospital. Often there is a fee. Be aware that the maximum fee that by law can be charged for medical records is seventy-five cents per page.
Finally, the patient should always bring the doctor a list of all medications, including over-the-counter medications, vitamins, dietary supplements, and/or herbal remedies, that he is taking. The more comprehensive the information the patient provides, the more accurate the specialist’s advice will be.
FINDING SECOND OPINIONS
If a patient is not comfortable with the advice he receives from a specialist, it is advisable to seek another opinion. Always make sure that a second opinion is provided by a doctor whose knowledge of liver disease is superior to, or at least equal to, that of the first specialist. However, patients should keep multiple opinions in perspective. Under no circumstances should patients ever make it their objective to shop around for opinions until they hear the diagnosis or prognosis that they are looking for. A game plan of this nature could only cause a serious illness to be left neglected, untreated, or treated inappropriately. It is natural for anyone to hope to hear that there is nothing wrong and that a liver biopsy and treatment aren’t necessary. In some cases, these statements may in fact be accurate; however, if the patient has seen two or three well-respected liver specialists, all of whom concur that something is wrong, the patient must accept that he has a chronic illness that may require treatment.
Source
New hepatitis C drug offers cure for more patients
Published on 17/12/10 at 10:38am
A new treatment from Janssen which could help cure many more patients with hepatitis C has been submitted in Europe.
Telaprevir is an oral, direct-acting antiviral that treats chronic genotype 1 hepatitis C virus (HCV), the most common form of the virus. Europe's regulator the EMA will fast-track the drug's appraisal, in recognition of its potential to significantly improve treatment of the disease.
Current standard treatment of HCV is pegylated-interferon and ribavirin, but only 40-50% of patients see the virus suppressed to levels where they are considered to be cured.
Clinical trials of telaprevir have shown spectacular results when added to standard therapy, with the drug raising cure rates from 44% to 75 per cent. Moreover the drug achieved these results by 24 weeks, half the time taken by current standard therapy.
The treatment has also shown to help treatment-naïve patients and those who have failed to respond to standard therapy.
The impressive results have led some analysts to predict peak sales of up to $3 billion.
The drug was discovered by Vertex, and is being marketed in Europe by Janssen.
Telaprevir has direct competition in the form of Merck’s boceprevir, which is in the same protease inhibitor class, and is expected to be filed with regulators very shortly.
“Current treatment for hepatitis is lengthy and only effective for approximately half of treatment-naïve patients, and even fewer patients who failed previous treatment,” commented Stefan Zeuzem, Professor of Medicine and chief, department of medicine, J W Goethe University Hospital, Frankfurt.
“If approved, telaprevir would help to significantly improve cure rates and shorten treatment duration for many people living with HCV, compared to current standard treatment.”
Johan Van Hoof, global therapeutic area head infectious diseases and vaccines at Janssen, called the filing a 'landmark' in the HCV treatment and said it demonstrated Janssen's dedication to addressing unmet medical need in infectious diseases.
An estimated 170 million people are living with HCV around the world, including more than five million in Europe.
Chronic HCV can result in serious long-term health problems, and an estimated 30% of patients will develop progressive liver disease, including cirrhosis of the liver, which places them at risk for liver insufficiency and liver cancer. HCV is the most common cause of liver transplant in Europe.
Andrew McConaghie
Source
A new treatment from Janssen which could help cure many more patients with hepatitis C has been submitted in Europe.
Telaprevir is an oral, direct-acting antiviral that treats chronic genotype 1 hepatitis C virus (HCV), the most common form of the virus. Europe's regulator the EMA will fast-track the drug's appraisal, in recognition of its potential to significantly improve treatment of the disease.
Current standard treatment of HCV is pegylated-interferon and ribavirin, but only 40-50% of patients see the virus suppressed to levels where they are considered to be cured.
Clinical trials of telaprevir have shown spectacular results when added to standard therapy, with the drug raising cure rates from 44% to 75 per cent. Moreover the drug achieved these results by 24 weeks, half the time taken by current standard therapy.
The treatment has also shown to help treatment-naïve patients and those who have failed to respond to standard therapy.
The impressive results have led some analysts to predict peak sales of up to $3 billion.
The drug was discovered by Vertex, and is being marketed in Europe by Janssen.
Telaprevir has direct competition in the form of Merck’s boceprevir, which is in the same protease inhibitor class, and is expected to be filed with regulators very shortly.
“Current treatment for hepatitis is lengthy and only effective for approximately half of treatment-naïve patients, and even fewer patients who failed previous treatment,” commented Stefan Zeuzem, Professor of Medicine and chief, department of medicine, J W Goethe University Hospital, Frankfurt.
“If approved, telaprevir would help to significantly improve cure rates and shorten treatment duration for many people living with HCV, compared to current standard treatment.”
Johan Van Hoof, global therapeutic area head infectious diseases and vaccines at Janssen, called the filing a 'landmark' in the HCV treatment and said it demonstrated Janssen's dedication to addressing unmet medical need in infectious diseases.
An estimated 170 million people are living with HCV around the world, including more than five million in Europe.
Chronic HCV can result in serious long-term health problems, and an estimated 30% of patients will develop progressive liver disease, including cirrhosis of the liver, which places them at risk for liver insufficiency and liver cancer. HCV is the most common cause of liver transplant in Europe.
Andrew McConaghie
Source
December 16, 2010
Liver cancer in cirrhotic patients effectively treated with radiofrequency ablation
Public release date: 16-Dec-2010
Contact: Dawn Peters
healthnews@wiley.com
781-388-8408
Wiley-Blackwell
RFA highly valuable therapy for controlling cancerous nodules
Researchers from Italy determined that radiofrequency ablation (RFA) is a safe and effective therapy for managing hepatocellular carcinoma (HCC) in cirrhotic patients. The high repeatability of RFA is advantageous in controlling recurrences of cancerous tumors in the liver. Results of this 10-year retrospective study are available in the January 2011 issue of Hepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases (AASLD).
HCC is the third leading cause of death from cancer worldwide and according to the National Cancer Institute approximately 19,000 deaths due to liver and intrahepatic bile duct cancer occurred in the U.S. in 2010. Studies have shown that many patients with liver cancer also have underlying cirrhosis (scarring of the liver), which complicates cancer management and is often a direct cause of death. Current guidelines recommend surgical resection for early-stage HCC in patients who have adequate liver function and chemical or thermal tumor ablation in cases where surgery is not possible.
In order to evaluate the effectiveness of RFA in managing the initial HCC nodule and recurrences and its impact on survival, a research team led by Sandro Rossi, M.D., from the Policlinico San Matteo Foundation in Pavia, Italy conducted a retrospective study of 706 patients presenting with HCC from January 1998 through January 2008. Percutaneous or laparoscopic RFA was performed, producing one to three thermal lesions with each insertion. Major complications that threatened a patient's life, produced morbidity, or prolonged the hospital stay were assessed with abdominal ultrasound (3 and 24 hours post RFA), complete blood counts, lactic dehydrogenase, aminotransferase level, and Child-Pugh-related tests.
Researchers classified results as either complete responses (CRs)—no enhancing tissue at the tumor site and normalization of alpha-fetoprotein (AFP) levels; or incomplete responses (IRs)—enhancing tissue at the tumor site, persistently elevated AFP levels, or both. An IR to laparoscopic RFA was classified as treatment failure (TF). When IR was observed after percutaneous RFA, the procedure was repeated within 15 days. An IR to the second percutaneous RFA treatment was then classified as a TF, with these patients then receiving selective transarterial chemoembolization (sTACE).
Results showed that CRs were obtained in 696 patients (98.5%) and 465 (66.8%) of these patients experienced a first recurrence during follow-up (median-29 months). RFA was repeated in 323 (69%) of patients with first recurrence, restoring disease-free status in 318 (98%) cases. In 223 patients there was a second recurrence and RFA was repeated in 147 (66%), with disease-free status obtained in 145 (98%) of cases.
"RFA is safe and effective for managing HCC in patients with cirrhosis," confirmed Dr. Rossi. Overall, 1326 HCC nodules were managed with 1921 RFA sessions (percutaneous-1840; laparoscopic-81), with no procedure-related deaths, and fewer than 1.0% of sessions with major complications. After repeated RFAs the estimated 3-year overall and disease-free survival rates were 67% and 40%; 5-year rates were 68% and 38%.
The researchers noted that optimal treatment strategies for cirrhotic patients with HCC is limited by the unpredictability of tumor progression, tumor understaging, and substantial risk of death unrelated to HCC. "Our experience indicates that RFA should be the treatment of choice for patients with one or two small HCCs," concluded Dr. Rossi. "Further research focusing on identifying tumor cell markers and genetic profiles associated with HCC growth patterns will ultimately help to develop individualized treatment strategies for managing liver cancer."
###
"Repeated Radiofrequency Ablation for Management of Cirrhotic Patients with Small Hepatocellular Carcinomas: A Long-term Cohort Study." Sandro Rossi, Valentina Ravetta, Laura Rosa, Giorgia Ghittoni, Francesca Torello Viera, Francesco Garbagnati, Enrico Maria Silini, Paolo Dionigi, Fabrizio Calliada, Pietro Quaretti, Carmine Tinelli. Hepatology; Published Online: October 21, 2010 (DOI: 10.1002/hep.23965); Print Issue Date: January 2011. http://onlinelibrary.wiley.com/doi/10.1002/hep.23965/abstract.
This study is published in Hepatology. Media wishing to receive a PDF of this article may contact healthnews@wiley.com.
About the Journal
Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published on behalf of the American Association for the Study of Liver Diseases (AASLD). For more information, please visit http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1527-3350 .
About Wiley-Blackwell
Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world's leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit http://www.wileyblackwell.com/ or our new online platform, Wiley Online Library (wileyonlinelibrary.com), one of the world's most extensive multidisciplinary collections of online resources, covering life, health, social and physical sciences, and humanities.
Source
Contact: Dawn Peters
healthnews@wiley.com
781-388-8408
Wiley-Blackwell
RFA highly valuable therapy for controlling cancerous nodules
Researchers from Italy determined that radiofrequency ablation (RFA) is a safe and effective therapy for managing hepatocellular carcinoma (HCC) in cirrhotic patients. The high repeatability of RFA is advantageous in controlling recurrences of cancerous tumors in the liver. Results of this 10-year retrospective study are available in the January 2011 issue of Hepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases (AASLD).
HCC is the third leading cause of death from cancer worldwide and according to the National Cancer Institute approximately 19,000 deaths due to liver and intrahepatic bile duct cancer occurred in the U.S. in 2010. Studies have shown that many patients with liver cancer also have underlying cirrhosis (scarring of the liver), which complicates cancer management and is often a direct cause of death. Current guidelines recommend surgical resection for early-stage HCC in patients who have adequate liver function and chemical or thermal tumor ablation in cases where surgery is not possible.
In order to evaluate the effectiveness of RFA in managing the initial HCC nodule and recurrences and its impact on survival, a research team led by Sandro Rossi, M.D., from the Policlinico San Matteo Foundation in Pavia, Italy conducted a retrospective study of 706 patients presenting with HCC from January 1998 through January 2008. Percutaneous or laparoscopic RFA was performed, producing one to three thermal lesions with each insertion. Major complications that threatened a patient's life, produced morbidity, or prolonged the hospital stay were assessed with abdominal ultrasound (3 and 24 hours post RFA), complete blood counts, lactic dehydrogenase, aminotransferase level, and Child-Pugh-related tests.
Researchers classified results as either complete responses (CRs)—no enhancing tissue at the tumor site and normalization of alpha-fetoprotein (AFP) levels; or incomplete responses (IRs)—enhancing tissue at the tumor site, persistently elevated AFP levels, or both. An IR to laparoscopic RFA was classified as treatment failure (TF). When IR was observed after percutaneous RFA, the procedure was repeated within 15 days. An IR to the second percutaneous RFA treatment was then classified as a TF, with these patients then receiving selective transarterial chemoembolization (sTACE).
Results showed that CRs were obtained in 696 patients (98.5%) and 465 (66.8%) of these patients experienced a first recurrence during follow-up (median-29 months). RFA was repeated in 323 (69%) of patients with first recurrence, restoring disease-free status in 318 (98%) cases. In 223 patients there was a second recurrence and RFA was repeated in 147 (66%), with disease-free status obtained in 145 (98%) of cases.
"RFA is safe and effective for managing HCC in patients with cirrhosis," confirmed Dr. Rossi. Overall, 1326 HCC nodules were managed with 1921 RFA sessions (percutaneous-1840; laparoscopic-81), with no procedure-related deaths, and fewer than 1.0% of sessions with major complications. After repeated RFAs the estimated 3-year overall and disease-free survival rates were 67% and 40%; 5-year rates were 68% and 38%.
The researchers noted that optimal treatment strategies for cirrhotic patients with HCC is limited by the unpredictability of tumor progression, tumor understaging, and substantial risk of death unrelated to HCC. "Our experience indicates that RFA should be the treatment of choice for patients with one or two small HCCs," concluded Dr. Rossi. "Further research focusing on identifying tumor cell markers and genetic profiles associated with HCC growth patterns will ultimately help to develop individualized treatment strategies for managing liver cancer."
###
"Repeated Radiofrequency Ablation for Management of Cirrhotic Patients with Small Hepatocellular Carcinomas: A Long-term Cohort Study." Sandro Rossi, Valentina Ravetta, Laura Rosa, Giorgia Ghittoni, Francesca Torello Viera, Francesco Garbagnati, Enrico Maria Silini, Paolo Dionigi, Fabrizio Calliada, Pietro Quaretti, Carmine Tinelli. Hepatology; Published Online: October 21, 2010 (DOI: 10.1002/hep.23965); Print Issue Date: January 2011. http://onlinelibrary.wiley.com/doi/10.1002/hep.23965/abstract.
This study is published in Hepatology. Media wishing to receive a PDF of this article may contact healthnews@wiley.com.
About the Journal
Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published on behalf of the American Association for the Study of Liver Diseases (AASLD). For more information, please visit http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1527-3350 .
About Wiley-Blackwell
Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world's leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit http://www.wileyblackwell.com/ or our new online platform, Wiley Online Library (wileyonlinelibrary.com), one of the world's most extensive multidisciplinary collections of online resources, covering life, health, social and physical sciences, and humanities.
Source
December 15, 2010
SciClone Announces Topline Results From Phase 2b Clinical Trial of SCV-07 for Treatment of Chronic Hepatitis C
Posted on: Wed, 15 Dec 2010 16:10:32 EST
FOSTER CITY, CA, Dec 15, 2010 (MARKETWIRE via COMTEX) --
SciClone Pharmaceuticals, Inc. (NASDAQ: SCLN
PowerRating) today announced topline results from the Company's phase 2b clinical trial of SCV-07 for the treatment of hepatitis C (HCV). The study evaluated the safety and immunomodulatory effects of SCV-07 as a monotherapy and in combination with ribavirin in relapsed HCV patients. Study data demonstrated SCV-07 to be safe and well-tolerated at both administered doses. Topline results showed a clear biological signal from SCV-07 but did not meet the study's primary efficacy endpoint of a 2 log reduction in viral load from baseline level. A secondary measure of efficacy, defined as a reduction in viral load of greater than 0.5 log from baseline level, was seen in 38.5% of the low-dose patients (5/13) and in 44.4% of the high-dose patients (8/18). Additionally, while no patients in the low-dose group achieved greater than a 1 log reduction, 3 of the high-dose patients achieved greater than a 1 log reduction in viral load. This proof of concept study was designed to provide an estimate of SCV-07's treatment effect in relapsed HCV patients and guide further studies of SCV-07 in addressing this chronic infection.
"Although the data showed an interesting biological signal, due to the rapidly changing landscape of effective treatments which increase the complexity and risks of developing drugs in chronic HCV, we have decided not to continue development in this indication. On another front, we continue to be excited about the potential for SCV-07 in the prevention of oral mucositis in patients with head and neck cancer and the initiation of our phase 2b study, which should begin by early 2011," stated Friedhelm Blobel, Ph.D., President and Chief Executive Officer of SciClone. "Our primary focus remains on rapidly growing our commercially successful specialty pharmaceutical business in China and other key emerging markets to increase profitability and generate cash for our shareholders."
Study Design The phase 2b multicenter, multi-dose, open-label study was designed to evaluate the safety and immunomodulatory effects of SCV-07 as a monotherapy or in combination with ribavirin in non-cirrhotic patients with genotype 1 chronic HCV who have relapsed after at least 44 weeks of treatment with pegylated interferon and ribavirin. The study, which also monitored biomarkers of immune activation and HCV viral load dynamics, included two treatment cohorts of 20 patients each who received SCV-07 at a dose of either 0.1 mg/kg or 1.0 mg/kg. The eight week treatment period included four weeks of SCV-07 monotherapy followed by four weeks of SCV-07 in combination with ribavirin. The trial also included three follow-up visits within seven weeks after the completion of treatment.
About SCV-07 SCV-07 (gamma-D-glutamyl-L-tryptophan) is a small molecule which appears to stimulate the immune system through inhibition of STAT3 signaling and the resulting effects on T-helper 1 cells. SCV-07 has been shown to be efficacious in animal models of immune-sensitive diseases, including prevention of oral mucositis, treatment of cancer, viral infections, and enhancement of response to vaccines.
Additionally, SciClone is currently planning to initiate a phase 2b study of SCV-07 for the prevention of oral mucositis by early 2011. As compared to the company's recently completed phase 2a trial, the phase 2b study design is expected to include higher doses of SCV-07 and be adequately powered to demonstrate statistical significance. Additionally, researchers expect to continue to investigate the role of specific genetic profiles on patient response to SCV-07, as well as the potential link between cytokine activity and SCV-07's sub-cellular mechanism of action.
SCV-07 is protected by composition of matter patents as well as multiple method of treatment patents. SciClone has exclusive worldwide rights to SCV-07 outside of Russia, where the molecule has recently been approved for stimulation of depressed immune systems.
About SciClone SciClone Pharmaceuticals (NASDAQ: SCLN) is a revenue-generating, China-centric, specialty pharmaceutical company with a substantial international business and a product portfolio of novel therapies for cancer and infectious diseases. The Company is focused on continuing sales growth and executing a clinical development strategy with prudently managed costs. ZADAXIN(R) (thymalfasin) is approved in over 30 countries for the treatment of hepatitis B (HBV) and hepatitis C (HCV), certain cancers, and as a vaccine adjuvant. In addition to further studying thymalfasin's use as a vaccine enhancer, SciClone is planning to evaluate SCV-07 in a phase 2b trial to modify the course of oral mucositis in patients with head and neck cancer; and recently completed a phase 2b trial of SCV-07 for the treatment of HCV. The Company also has exclusive commercialization and distribution rights in China to a novel treatment for advanced liver cancer, DC Bead(R), currently under review by regulatory agencies in that country. Additionally, SciClone owns exclusive commercialization and distribution rights to the anti-nausea drug ondansetron RapidFilm(R) in China, including Hong Kong and Macau, and Vietnam. The Company intends to seek regulatory approval for the product, commonly used to treat and prevent nausea and vomiting caused by chemotherapy, radiotherapy, and surgery, in these markets. For additional information, please visit www.sciclone.com.
Forward-looking statements The information in this press release contains forward-looking statements, including our expectations and beliefs regarding the timing and results of our clinical trials. You are urged to consider statements that include the words "may," "will," "would," "could," "should," "might," "believes," "estimates," "projects," "potential," "expects," "plans," "anticipates," "intends," "continues," "forecast," "designed," "goal," or the negative of those words or other comparable words to be uncertain and forward-looking. These statements are subject to risks and uncertainties that are difficult to predict and actual outcomes may differ materially. These risks and uncertainties include our forward-looking statements regarding our commercial and development objectives because of uncertainties, including future sales, product pricing, the timing of clinical trial events such as patient enrollment, requirements of, and future actions of, the U.S. Food and Drug Administration, the fact that experimental data, and clinical results derived from studies with animals or a limited group of patients, as well as comparisons with other clinical trials, may not be predictive of the results of larger studies and, therefore, such experimental or clinical data are not necessarily predictive indicative of the efficacy or safety or the results of larger studies and clinical trials. Please also refer to the other risks and uncertainties described in SciClone's filings with the Securities and Exchange Commission. All forward-looking statements are based on information currently available to SciClone, and SciClone assumes no obligation to update any such forward-looking statements.
DC Bead is a registered trademark of Biocompatibles UK Limited.
RapidFilm is a registered trademark of Labtec Gesellschaft fuer technologische Forschung und Entwicklung mbH.
SOURCE: SciClone Pharmaceuticals, Inc.
Source
FOSTER CITY, CA, Dec 15, 2010 (MARKETWIRE via COMTEX) --
SciClone Pharmaceuticals, Inc. (NASDAQ: SCLN
PowerRating) today announced topline results from the Company's phase 2b clinical trial of SCV-07 for the treatment of hepatitis C (HCV). The study evaluated the safety and immunomodulatory effects of SCV-07 as a monotherapy and in combination with ribavirin in relapsed HCV patients. Study data demonstrated SCV-07 to be safe and well-tolerated at both administered doses. Topline results showed a clear biological signal from SCV-07 but did not meet the study's primary efficacy endpoint of a 2 log reduction in viral load from baseline level. A secondary measure of efficacy, defined as a reduction in viral load of greater than 0.5 log from baseline level, was seen in 38.5% of the low-dose patients (5/13) and in 44.4% of the high-dose patients (8/18). Additionally, while no patients in the low-dose group achieved greater than a 1 log reduction, 3 of the high-dose patients achieved greater than a 1 log reduction in viral load. This proof of concept study was designed to provide an estimate of SCV-07's treatment effect in relapsed HCV patients and guide further studies of SCV-07 in addressing this chronic infection.
"Although the data showed an interesting biological signal, due to the rapidly changing landscape of effective treatments which increase the complexity and risks of developing drugs in chronic HCV, we have decided not to continue development in this indication. On another front, we continue to be excited about the potential for SCV-07 in the prevention of oral mucositis in patients with head and neck cancer and the initiation of our phase 2b study, which should begin by early 2011," stated Friedhelm Blobel, Ph.D., President and Chief Executive Officer of SciClone. "Our primary focus remains on rapidly growing our commercially successful specialty pharmaceutical business in China and other key emerging markets to increase profitability and generate cash for our shareholders."
Study Design The phase 2b multicenter, multi-dose, open-label study was designed to evaluate the safety and immunomodulatory effects of SCV-07 as a monotherapy or in combination with ribavirin in non-cirrhotic patients with genotype 1 chronic HCV who have relapsed after at least 44 weeks of treatment with pegylated interferon and ribavirin. The study, which also monitored biomarkers of immune activation and HCV viral load dynamics, included two treatment cohorts of 20 patients each who received SCV-07 at a dose of either 0.1 mg/kg or 1.0 mg/kg. The eight week treatment period included four weeks of SCV-07 monotherapy followed by four weeks of SCV-07 in combination with ribavirin. The trial also included three follow-up visits within seven weeks after the completion of treatment.
About SCV-07 SCV-07 (gamma-D-glutamyl-L-tryptophan) is a small molecule which appears to stimulate the immune system through inhibition of STAT3 signaling and the resulting effects on T-helper 1 cells. SCV-07 has been shown to be efficacious in animal models of immune-sensitive diseases, including prevention of oral mucositis, treatment of cancer, viral infections, and enhancement of response to vaccines.
Additionally, SciClone is currently planning to initiate a phase 2b study of SCV-07 for the prevention of oral mucositis by early 2011. As compared to the company's recently completed phase 2a trial, the phase 2b study design is expected to include higher doses of SCV-07 and be adequately powered to demonstrate statistical significance. Additionally, researchers expect to continue to investigate the role of specific genetic profiles on patient response to SCV-07, as well as the potential link between cytokine activity and SCV-07's sub-cellular mechanism of action.
SCV-07 is protected by composition of matter patents as well as multiple method of treatment patents. SciClone has exclusive worldwide rights to SCV-07 outside of Russia, where the molecule has recently been approved for stimulation of depressed immune systems.
About SciClone SciClone Pharmaceuticals (NASDAQ: SCLN) is a revenue-generating, China-centric, specialty pharmaceutical company with a substantial international business and a product portfolio of novel therapies for cancer and infectious diseases. The Company is focused on continuing sales growth and executing a clinical development strategy with prudently managed costs. ZADAXIN(R) (thymalfasin) is approved in over 30 countries for the treatment of hepatitis B (HBV) and hepatitis C (HCV), certain cancers, and as a vaccine adjuvant. In addition to further studying thymalfasin's use as a vaccine enhancer, SciClone is planning to evaluate SCV-07 in a phase 2b trial to modify the course of oral mucositis in patients with head and neck cancer; and recently completed a phase 2b trial of SCV-07 for the treatment of HCV. The Company also has exclusive commercialization and distribution rights in China to a novel treatment for advanced liver cancer, DC Bead(R), currently under review by regulatory agencies in that country. Additionally, SciClone owns exclusive commercialization and distribution rights to the anti-nausea drug ondansetron RapidFilm(R) in China, including Hong Kong and Macau, and Vietnam. The Company intends to seek regulatory approval for the product, commonly used to treat and prevent nausea and vomiting caused by chemotherapy, radiotherapy, and surgery, in these markets. For additional information, please visit www.sciclone.com.
Forward-looking statements The information in this press release contains forward-looking statements, including our expectations and beliefs regarding the timing and results of our clinical trials. You are urged to consider statements that include the words "may," "will," "would," "could," "should," "might," "believes," "estimates," "projects," "potential," "expects," "plans," "anticipates," "intends," "continues," "forecast," "designed," "goal," or the negative of those words or other comparable words to be uncertain and forward-looking. These statements are subject to risks and uncertainties that are difficult to predict and actual outcomes may differ materially. These risks and uncertainties include our forward-looking statements regarding our commercial and development objectives because of uncertainties, including future sales, product pricing, the timing of clinical trial events such as patient enrollment, requirements of, and future actions of, the U.S. Food and Drug Administration, the fact that experimental data, and clinical results derived from studies with animals or a limited group of patients, as well as comparisons with other clinical trials, may not be predictive of the results of larger studies and, therefore, such experimental or clinical data are not necessarily predictive indicative of the efficacy or safety or the results of larger studies and clinical trials. Please also refer to the other risks and uncertainties described in SciClone's filings with the Securities and Exchange Commission. All forward-looking statements are based on information currently available to SciClone, and SciClone assumes no obligation to update any such forward-looking statements.
DC Bead is a registered trademark of Biocompatibles UK Limited.
RapidFilm is a registered trademark of Labtec Gesellschaft fuer technologische Forschung und Entwicklung mbH.
SOURCE: SciClone Pharmaceuticals, Inc.
Source
Ontarians deserve better access to treatment for hepatitis B and C
December 15, 2010
ICES study calls for more prevention, more screening and more research but what about treatment?
Toronto, December 15, 2010: Hepatitis B and C are insidious diseases that have few symptoms until they reach an advanced and potentially fatal stage. The time it takes for these diseases to cause cirrhosis or liver cancer may be anywhere from two to 20 years -- more than enough time to intervene. Simple blood tests can identify the hepatitis B and C viruses and yet these tests are not a standard part of annual physicals. Effective treatments also exist for both chronic hepatitis B and C but they are not always accessible to those who need them. With the recent Institute of Clinical Evaluative Sciences (ICES) study ranking hepatitis B and C in the top five most burdensome infectious diseases, the Canadian Liver Foundation is calling upon the provincial government to establish standardized screening protocols and to make treatment more widely accessible for all Ontarians with hepatitis B and C.
“The ICES study should be an eye-opener for everyone,” says Dr. Morris Sherman, Chairman of the Canadian Liver Foundation and a hepatologist at Toronto General Hospital. “It shows that hepatitis B and C are major contributors to morbidity and mortality in Ontario. These diseases have not been a priority for our government despite the major toll they take on our population. The tragedy is that the power to reduce this human cost is within the grasp of government but they have yet to recognize it.”
The study calls for greater screening and preventative measures like immunization (in the case of hepatitis B) to tackle the problem. It is estimated that as many as one third of Ontarians with viral hepatitis do not realize that they have it. If all physicians incorporated hepatitis testing into standard physicals, more patients would be identified and those that had not been exposed to hepatitis B could be immunized. These measures would increase the early identification and intervention but are only part of the solution. Once identified, patients need to have access to affordable treatments in order to prevent the more serious consequences of their disease.
Hepatitis B is the leading cause of liver cancer – a form of cancer that is on the rise in Ontario. If diagnosed at an early stage however, hepatitis B and even liver cancer can be treated effectively. “There are excellent treatments available for hepatitis B that will prevent most of the potentially fatal complications of this disease,” says Dr. Sherman. “And yet, restrictions on funding for treatment exist in most provinces and in Ontario, those restrictions are so tight that most patients who need treatment cannot get reimbursement through the government. With a high proportion of hepatitis B patients coming from the Chinese immigrant community, these policies are particularly discriminatory. Without access to affordable and effective treatments, hepatitis B will continue to contribute to mortality in this province.”
The Canadian Liver Foundation agrees with the report’s recommendation for more funding for research. Hepatitis C is a good example of how investment in research can pay off in a short amount of time. From the virus first being identified in the 1980s, hepatitis C has seen dramatic steps forward in treatment with more on the way. “Improved treatment for hepatitis C is just a few years away,” says Dr. Sherman. “With these new treatments the cure rate will go up from about 45% to 75%. These breakthroughs will give us tremendous opportunity to reduce the burden of this disease but only if the treatments are available to patients regardless of their financial resources.”
“The ICES study sheds light on serious health issues that the Canadian Liver Foundation and the hepatology community have been aware of for some time,” says Dr. Sherman. “While we hope that this report will help open a dialogue on the financial and human costs of hepatitis B and C in this province, we call upon the government to act now to make appropriate treatment for hepatitis B and hepatitis C available to all those who need it to mitigate the effects of these diseases. If this study is repeated in the future, we do not want to see hepatitis B and hepatitis C in the top 10.”
For more information, contact
Melanie Kearns
416-491-3353 ext. 4923
mkearns@liver.ca
Source
ICES study calls for more prevention, more screening and more research but what about treatment?
Toronto, December 15, 2010: Hepatitis B and C are insidious diseases that have few symptoms until they reach an advanced and potentially fatal stage. The time it takes for these diseases to cause cirrhosis or liver cancer may be anywhere from two to 20 years -- more than enough time to intervene. Simple blood tests can identify the hepatitis B and C viruses and yet these tests are not a standard part of annual physicals. Effective treatments also exist for both chronic hepatitis B and C but they are not always accessible to those who need them. With the recent Institute of Clinical Evaluative Sciences (ICES) study ranking hepatitis B and C in the top five most burdensome infectious diseases, the Canadian Liver Foundation is calling upon the provincial government to establish standardized screening protocols and to make treatment more widely accessible for all Ontarians with hepatitis B and C.
“The ICES study should be an eye-opener for everyone,” says Dr. Morris Sherman, Chairman of the Canadian Liver Foundation and a hepatologist at Toronto General Hospital. “It shows that hepatitis B and C are major contributors to morbidity and mortality in Ontario. These diseases have not been a priority for our government despite the major toll they take on our population. The tragedy is that the power to reduce this human cost is within the grasp of government but they have yet to recognize it.”
The study calls for greater screening and preventative measures like immunization (in the case of hepatitis B) to tackle the problem. It is estimated that as many as one third of Ontarians with viral hepatitis do not realize that they have it. If all physicians incorporated hepatitis testing into standard physicals, more patients would be identified and those that had not been exposed to hepatitis B could be immunized. These measures would increase the early identification and intervention but are only part of the solution. Once identified, patients need to have access to affordable treatments in order to prevent the more serious consequences of their disease.
Hepatitis B is the leading cause of liver cancer – a form of cancer that is on the rise in Ontario. If diagnosed at an early stage however, hepatitis B and even liver cancer can be treated effectively. “There are excellent treatments available for hepatitis B that will prevent most of the potentially fatal complications of this disease,” says Dr. Sherman. “And yet, restrictions on funding for treatment exist in most provinces and in Ontario, those restrictions are so tight that most patients who need treatment cannot get reimbursement through the government. With a high proportion of hepatitis B patients coming from the Chinese immigrant community, these policies are particularly discriminatory. Without access to affordable and effective treatments, hepatitis B will continue to contribute to mortality in this province.”
The Canadian Liver Foundation agrees with the report’s recommendation for more funding for research. Hepatitis C is a good example of how investment in research can pay off in a short amount of time. From the virus first being identified in the 1980s, hepatitis C has seen dramatic steps forward in treatment with more on the way. “Improved treatment for hepatitis C is just a few years away,” says Dr. Sherman. “With these new treatments the cure rate will go up from about 45% to 75%. These breakthroughs will give us tremendous opportunity to reduce the burden of this disease but only if the treatments are available to patients regardless of their financial resources.”
“The ICES study sheds light on serious health issues that the Canadian Liver Foundation and the hepatology community have been aware of for some time,” says Dr. Sherman. “While we hope that this report will help open a dialogue on the financial and human costs of hepatitis B and C in this province, we call upon the government to act now to make appropriate treatment for hepatitis B and hepatitis C available to all those who need it to mitigate the effects of these diseases. If this study is repeated in the future, we do not want to see hepatitis B and hepatitis C in the top 10.”
For more information, contact
Melanie Kearns
416-491-3353 ext. 4923
mkearns@liver.ca
Source
How Long Does HCV Live on Surfaces?
Alan Franciscus, Editor-in-Chief
HCV Advocate
How long is HCV stable on exposed (environmental) surfaces? In real world situations it would be almost impossible to effectively study this problem because of the many variables involved in testing blood on exposed surfaces, such as room temperature, amount of blood exposed, viral load (low/high) and various contaminants in the environment. However, a study conducted by the Centers for Disease Control may shed some light on this issue and help provide a better understanding of the infectivity of HCV on surfaces, which will help fine tune HCV prevention measures.
A study conducted by Kris Krawczynski et. al from the Centers for Disease Control and Prevention tested the stability of dried and stored serum (blood) of HCV infected blood in chimpanzees to determine how long HCV infected blood lives on an outside surface as well as the level of infectivity of the blood exposed.
Chimpanzee plasma (CID) divided into 105 infectious doses (genotype 1a) was dried in tubes under vacuum. After overnight drying (~16 hours) samples were either rehydrated with sterile water and stored at -70C or transferred to a controlled environmental chamber (42% humidity, over saturated salt solution) for a 4 or 7 day storage at 25C and subsequently rehydrated with sterile water and kept at -70C.
Samples dried/stored 7 days and dried overnight were used for testing. To determine infectivity, samples of dried/stored plasma for 7 days, 4 days and overnight, were reconstituted in sterile water and injected into a chimpanzee. The size of the infectious dose of each inoculum was calculated at 3.3 x 104 CID. Plasma samples were tested for HCV RNA (viral load), HCV anti-body and alanine aminotransferase (ALT) levels twice weekly. In addition, liver specimens were obtained weekly or biweekly and tested for hepatitis C virus antigen (HCVAg) and histopathology (liver health).
The chimpanzee was first inoculated with the HCV inoculum that was dried and stored for 7 days and followed during 129 days. Subsequently, the chimpanzee was inoculated with the HCV inoculum that was dried and stored for 4 days and followed for 134 days, and finally inoculated with the dried sample overnight and followed for 201 days. Data from three chimpanzees with untreated HCV inoculum were included in the study as a control group.
The authors found that HCV RNA (viral load) was detectable in plasma dried overnight and 7 days, but a ten fold decrease of detectable HCV RNA (viral load) was found in both of the samples compared with the HCV RNA level of the original, untreated HCV positive plasma sample. No evidence of HCV infections was detected in the chimpanzee given either the 7-day or 4-day dried and stored samples. All blood samples tested were negative for HCV RNA and HCV antibodies. In addition, ALT levels remained in the normal range. However after inoculation with the overnight dried sample, HCV RNA was detected in the blood of the chimpanzee from day 7 post inoculation and viral load reached 6.0 to 7.3 logs IU/mL. HCV Ag positive hepatocytes (liver cells) were observed from day 11 post inoculation, seroconversion to anti-HCV was observed on day 127, and the chimpanzee was still positive for HCV RNA (4.8 logs IU/mL) at day 201 post infection. ALT activity level was elevated over the normal range from day 11 post inoculation and remained elevated until the end of the observation period. Virologic, serologic, and clinical evidence of HCV infection and acute hepatitis was found in all three control animals.
The Bottom Line
The authors of this study concluded that infectivity studies in a chimpanzee suggest that HCV may survive on environmental surfaces at room temperature for at least 16 hours but not longer than 4 days. The potential for HCV to survive in the environment re-emphasizes the importance of cleaning and disinfection procedures, safe therapeutic injection practices, and harm reduction counseling and services for injection drug users.
Source
Also See:
HCV Outside the Body: How Well Does It Survive on Surfaces, in Syringes, and in the Lab?
HCV Advocate
How long is HCV stable on exposed (environmental) surfaces? In real world situations it would be almost impossible to effectively study this problem because of the many variables involved in testing blood on exposed surfaces, such as room temperature, amount of blood exposed, viral load (low/high) and various contaminants in the environment. However, a study conducted by the Centers for Disease Control may shed some light on this issue and help provide a better understanding of the infectivity of HCV on surfaces, which will help fine tune HCV prevention measures.
A study conducted by Kris Krawczynski et. al from the Centers for Disease Control and Prevention tested the stability of dried and stored serum (blood) of HCV infected blood in chimpanzees to determine how long HCV infected blood lives on an outside surface as well as the level of infectivity of the blood exposed.
Chimpanzee plasma (CID) divided into 105 infectious doses (genotype 1a) was dried in tubes under vacuum. After overnight drying (~16 hours) samples were either rehydrated with sterile water and stored at -70C or transferred to a controlled environmental chamber (42% humidity, over saturated salt solution) for a 4 or 7 day storage at 25C and subsequently rehydrated with sterile water and kept at -70C.
Samples dried/stored 7 days and dried overnight were used for testing. To determine infectivity, samples of dried/stored plasma for 7 days, 4 days and overnight, were reconstituted in sterile water and injected into a chimpanzee. The size of the infectious dose of each inoculum was calculated at 3.3 x 104 CID. Plasma samples were tested for HCV RNA (viral load), HCV anti-body and alanine aminotransferase (ALT) levels twice weekly. In addition, liver specimens were obtained weekly or biweekly and tested for hepatitis C virus antigen (HCVAg) and histopathology (liver health).
The chimpanzee was first inoculated with the HCV inoculum that was dried and stored for 7 days and followed during 129 days. Subsequently, the chimpanzee was inoculated with the HCV inoculum that was dried and stored for 4 days and followed for 134 days, and finally inoculated with the dried sample overnight and followed for 201 days. Data from three chimpanzees with untreated HCV inoculum were included in the study as a control group.
The authors found that HCV RNA (viral load) was detectable in plasma dried overnight and 7 days, but a ten fold decrease of detectable HCV RNA (viral load) was found in both of the samples compared with the HCV RNA level of the original, untreated HCV positive plasma sample. No evidence of HCV infections was detected in the chimpanzee given either the 7-day or 4-day dried and stored samples. All blood samples tested were negative for HCV RNA and HCV antibodies. In addition, ALT levels remained in the normal range. However after inoculation with the overnight dried sample, HCV RNA was detected in the blood of the chimpanzee from day 7 post inoculation and viral load reached 6.0 to 7.3 logs IU/mL. HCV Ag positive hepatocytes (liver cells) were observed from day 11 post inoculation, seroconversion to anti-HCV was observed on day 127, and the chimpanzee was still positive for HCV RNA (4.8 logs IU/mL) at day 201 post infection. ALT activity level was elevated over the normal range from day 11 post inoculation and remained elevated until the end of the observation period. Virologic, serologic, and clinical evidence of HCV infection and acute hepatitis was found in all three control animals.
The Bottom Line
The authors of this study concluded that infectivity studies in a chimpanzee suggest that HCV may survive on environmental surfaces at room temperature for at least 16 hours but not longer than 4 days. The potential for HCV to survive in the environment re-emphasizes the importance of cleaning and disinfection procedures, safe therapeutic injection practices, and harm reduction counseling and services for injection drug users.
Source
Also See:
HCV Outside the Body: How Well Does It Survive on Surfaces, in Syringes, and in the Lab?
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