By Lois Wingerson
August 17, 2010
We cannot escape the realities of biology. Just as children rescued from leukemia and lymphoma live to grow into adults who must confront the adverse effects of their curative treatment, people rescued from AIDS by HAART (highly active antiretroviral therapy) are showing a substantially increased risk of cancers other than the "AIDS-defining" malignancies designated by the Centers for Disease Control in the 1980s: Kaposi sarcoma, non-Hodgkin lymphoma (NHL), and cervical cancer.
With increasing numbers of people surviving for long periods whose immune systems have been weakened by HIV, we can expect to witness an increased incidence of this spectrum of "non-AIDS defining" cancers, or NADCs. This is the independent conclusion from unrelated studies in the United States and Switzerland, which show nearly identical increases in the risk of Hodgkin lymphoma and anal cancer many years after the initiation of HAART therapy.
The US-based AIDS Malignancy Consortium has referred to a coming "epidemic" of these cancers. "NADCs are here to stay," remarked immunologist Dirk Dittmer PhD of the Center for AIDS Research at the University of North Carolina, Chapel Hill, in an editorial about the US study.
That study, apparently the largest and longest-term comparison to date matching cancer rates among HIV+ people with those of other cancer patients, used records from a national cancer registry and those of more than 260,000 adults and adolescents diagnosed with AIDS or HIV-positive status between 1980 and 2008. Thus it can speak to the experience of people who have lived as long as 10 years after diagnosis.
The new analysis of data from the NCI-sponsored HIV-AIDS Cancer Match Study appears this month in the Archives of Internal Medicine.
The latest results from the analogous but smaller Swiss HIV Cohort Study were published last month in the British Journal of Cancer. The investigators from the International Agency for Research on Cancer (IARC) matched records from 9,429 persons with HIV or AIDS against data from a Swiss cancer registry.
"By and large, we all agree that several cancers (especially those associated with HPV [human papilloma virus] and HBV/HCV [hepatitis B and hepatitis C virus]) are going to increase in people with HIV and AIDS unless effective screening/treatment of cancer-associated infections are found and implemented," said two of the IARC authors, Silvia Franceschi and Gary Clifford, when asked to compare the two studies.
The NCI researchers found a decline in Kaposi sarcoma (KS) and the AIDS-associated varieties of NHL during the study period, presumably due to the effects of HAART treatment. But there was an overall increase of 20% in non-AIDS defining cancers during the HAART era. The incidence of Hodgkin lymphoma doubled (most commonly the mixed-cellularity type associated with the Epstein-Barr virus). The incidence of anal cancer in this population tripled between the non-HAART and the HAART era, with a relative risk about 30 times that of the general population.
The IARC study also showed a decline in KS and NHL, accompanied by an increase in NADCs to a level approximately double that of the general population.
It is important not to attribute to HAART any "unproven responsibility" for these recent upward trends in NADCs, Franceschi and Clifford remarked. The increase in risk of NADCs can likely be attributed to "age as a proxy of duration of exposure to cancer-causing chronic infections … that are much more common in people with HIV and AIDS than in the general population, and are characterized by long latent phases," they added.
In other words, the oncogenic events that trigger these cancers may happen even before HIV infection is discovered (as the NCI authors also observed). A weakened immune system predisposes to the NADC malignancy, and HAART treatment allows it the time to develop.
Environmental factors implicit in HIV infection—specifically sexual practices and intravenous drug use—might equally play a role, the NCI authors observed, given that most of the NADCs involve the anal and genital regions, the mouth, throat, and tongue, and the blood.
After the advent of HAART, anal cancer became as prevalent as KS and NHL among AIDS/HIV patients. It may be time to add anal cancer to the AIDS-defining malignancies, Dittmer speculated in his editorial. It's also important not to minimize their total impact, he added in an email. "Despite their relative decline, AIDS defining cancers (Kaposi sarcoma and NHL) still account for more diagnosis than any one other cancer," Dittmer wrote. "The AIDS-related cancers are here to stay as well, as new people continue to be infected with HIV."
HAART is not to blame, exactly, but it must be accounted for in using chemotherapy to treat NADCs. Look for results from a collaborative study assessing the effects of HAART on the effects of cancer chemotherapy with the tyrosine kinase inhibitor sutinib maleate. Recruitment is scheduled to close next month. According to a report at this year's annual meeting of the American Society for Clinical Oncology, so far the drug has been well tolerated in this scenario and pharmacokinetic information is being analyzed.
Source
August 17, 2010
Dental problems delaying the initiation of interferon therapy for HCV-infected patients
There has been little discussion about the importance of oral management and interferon (IFN) therapy, although management of the side effects of therapy for chronic hepatitis C has been documented.This study determined whether dental problems delayed the initiation of IFN therapy for hepatitis C virus (HCV)-infected patients.
Results: We analyzed 570 HCV-infected patients who were admitted to our hospital from December 2003 to June 2010 for treatment consisting of pegylated IFN (Peg-IFN) monotherapy or Peg-IFN/ribavirin combination therapy. The group comprised 274 men and 296 women with a mean age 57.2 years.
Of the 570 patients, six could not commence Peg-IFN therapy, despite their admission, because of dental problems such as periodontitis, pupitis, and pericoronitis. The ages of six whose dental problems delayed the initiation of Peg-IFN ranged from 25 to 67 years, with a mean age of 47.3 +/- 15.2 years.
IFN therapy was deferred for 61.3 +/- 47.7 days. Among the six subjects for whom IFN treatment was delayed, only one had a salivary flow that was lower than the normal value.
Conclusions: Treatment of dental infections is required before IFN therapy for HCV infection can be started.
To increase the depth of understanding of oral health care, it is hoped that dentists and medical specialists in all areas will hold discussions to generate cooperation.
Author: Yumiko NagaoMichio Sata
Credits/Source: Virology Journal 2010, 7:192
Published on: 2010-08-17
Source
Results: We analyzed 570 HCV-infected patients who were admitted to our hospital from December 2003 to June 2010 for treatment consisting of pegylated IFN (Peg-IFN) monotherapy or Peg-IFN/ribavirin combination therapy. The group comprised 274 men and 296 women with a mean age 57.2 years.
Of the 570 patients, six could not commence Peg-IFN therapy, despite their admission, because of dental problems such as periodontitis, pupitis, and pericoronitis. The ages of six whose dental problems delayed the initiation of Peg-IFN ranged from 25 to 67 years, with a mean age of 47.3 +/- 15.2 years.
IFN therapy was deferred for 61.3 +/- 47.7 days. Among the six subjects for whom IFN treatment was delayed, only one had a salivary flow that was lower than the normal value.
Conclusions: Treatment of dental infections is required before IFN therapy for HCV infection can be started.
To increase the depth of understanding of oral health care, it is hoped that dentists and medical specialists in all areas will hold discussions to generate cooperation.
Author: Yumiko NagaoMichio Sata
Credits/Source: Virology Journal 2010, 7:192
Published on: 2010-08-17
Source
Studies Confirm Genetic Link to Advanced Fatty Liver Disease
17 August 2010 Wiley - Blackwell
Genome-Wide Study Identifies an Important Genetic Variant Associated with NAFLD
Researchers at Massachusetts General Hospital found that patients with nonalcoholic fatty liver disease (NAFLD) who carry an allele of the PNPLA3 gene have an increased risk of developing advanced disease, including nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. A second study supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) validates these findings and further concludes that in pediatric patients, the same allele is associated with earlier disease presentation. Both studies are available in the September issue of Hepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases (AASLD).
NAFLD is the most common cause of chronic liver disease and afflicts an estimated 20%-30% of the general population and 67%-75% of the obese population. The precise mechanism responsible for the development of the NASH phenotype is yet to be clarified. Genome-wide association (GWA) studies are an important initial step in the identification of these genetic factors because they evaluate the genotypic-phenotypic association in large population-based cohorts and have identified susceptibility loci in numerous diseases.
Recently, GWA studies identified an important genetic variant associated with the presence of NAFLD. Whether these genetic variants also determine disease severity is unknown. To find out, researchers at the NIDDK evaluated single nucleotide polymorphism (SNP) genotypes in 894 primarily Caucasian adults, compared with a control group of 336 Caucasians. The patient population was recruited from 1 of 3 National Institutes of Health (NIH) sponsored NASH-Clinical Research Network (NASH-CRN) multicenter studies, as well as a cohort of individuals with NASH at the NIH Clinical Center. Study participants had histological evidence of NAFLD or NASH determined by biopsy obtained prior to enrollment. The focus of the study was the PNPLA3 locus on chromosome 22, and especially the non-synonymous coding SNP rs738409 G.
Results indicate that the rs738409 G allele was significantly associated with increased steatosis, portal inflammation, and lobular inflammation. For all of these parameters, genotypes containing rs738409 G were associated with more severe disease. After adjustment for age, gender, body mass index (BMI), diabetes type 2 and alcohol consumption, all associations remained significant.
“Our findings suggest that the rs738409 G allele may predispose patients to fat accumulation in the liver, but that other factors, environmental or hereditary, may be required for the development of inflammation, cellular injury and fibrosis,” says study leader T. Jake Liang, M.D. “However, once patients develop NASH, the rs738409 G allele predisposes them to more severe injury.”
NAFLD is becoming increasingly prevalent in pediatric patients, prompting the researchers to also search for an association between the PNPLA3 SNPs and disease severity in 223 children enrolled in the same study groups as the adults. While no association was found, the presence of the rs738409 G allele was associated with a younger age at the time of liver biopsy, suggesting a younger age of disease presentation.
Concurrent research at Massachusetts General Hospital also identified the G allele of rs738409 in PNPLA3 as a potential risk factor for NAFLD. The Mass General team examined SNPs at 7 loci associated with steatosis in 592 patients of European ancestry from the CRN and 1,405 ancestry-matched controls from the MIGen study. No association was observed between rs738409 G and BMI, triglyceride levels, and high and low-density lipoprotein levels, or diabetes. None of the variants at the other six other loci were associated with NAFLD.
The results suggest that certain inherited variations in lipid metabolism precede and could lead to the development of liver disease. The analysis indicates that genetic variation at PNPLA3 confers a markedly increased risk of severe histological features of NAFLD, without a strong effect on metabolic syndrome component traits. Given that PNPLA3 appears to be part of a family of enzymes that affect lipid metabolism, this suggests that altering lipid metabolism, particularly within the liver, can affect accumulation of fat and subsequent development of NAFLD.
Study leader Elizabeth Speliotes, M.D., Ph.D., M.Ph., concludes, “Through genetic analyses, we may be able to delineate the causal pathways that lead to specific disease complications of metabolic risk factors such as NAFLD and, in the future, selectively target them for therapeutic intervention.”
Full bibliographic information
Article: “PNPLA3 Variants Specifically Confer Increased Risk for Histologic NAFLD but Not Metabolic Disease.” Elizabeth K. Speliotes, Johannah L. Butler, Cameron Palmer, Benjamin F. Voight, the GIANT Consortium, the MIGen Consortium, the NASH CRN, Joel N. Hirschhorn. Hepatology; Published Online: May 18, 2010 (DOI: 10.1002/hep.23768); Print Issue Date: September 2010. http://onlinelibrary.wiley.com/doi/10.1002/hep.23768/abstract
Article: “The Association of Genetic Variability in PNPLA3 with Histological Severity of Non-Alcoholic Fatty Liver Disease.” Yaron Rotman, Christopher Koh, Joseph M. Zmuda, David E. Kleiner, T. Jake Liang, and the NASH CRN. Hepatology; Published Online: May 14, 2010 (DOI: 10.1002/hep.23759); Print Issue Date: September 2010. http://onlinelibrary.wiley.com/doi/10.1002/hep.23759/abstract
Source
Genome-Wide Study Identifies an Important Genetic Variant Associated with NAFLD
Researchers at Massachusetts General Hospital found that patients with nonalcoholic fatty liver disease (NAFLD) who carry an allele of the PNPLA3 gene have an increased risk of developing advanced disease, including nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. A second study supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) validates these findings and further concludes that in pediatric patients, the same allele is associated with earlier disease presentation. Both studies are available in the September issue of Hepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases (AASLD).
NAFLD is the most common cause of chronic liver disease and afflicts an estimated 20%-30% of the general population and 67%-75% of the obese population. The precise mechanism responsible for the development of the NASH phenotype is yet to be clarified. Genome-wide association (GWA) studies are an important initial step in the identification of these genetic factors because they evaluate the genotypic-phenotypic association in large population-based cohorts and have identified susceptibility loci in numerous diseases.
Recently, GWA studies identified an important genetic variant associated with the presence of NAFLD. Whether these genetic variants also determine disease severity is unknown. To find out, researchers at the NIDDK evaluated single nucleotide polymorphism (SNP) genotypes in 894 primarily Caucasian adults, compared with a control group of 336 Caucasians. The patient population was recruited from 1 of 3 National Institutes of Health (NIH) sponsored NASH-Clinical Research Network (NASH-CRN) multicenter studies, as well as a cohort of individuals with NASH at the NIH Clinical Center. Study participants had histological evidence of NAFLD or NASH determined by biopsy obtained prior to enrollment. The focus of the study was the PNPLA3 locus on chromosome 22, and especially the non-synonymous coding SNP rs738409 G.
Results indicate that the rs738409 G allele was significantly associated with increased steatosis, portal inflammation, and lobular inflammation. For all of these parameters, genotypes containing rs738409 G were associated with more severe disease. After adjustment for age, gender, body mass index (BMI), diabetes type 2 and alcohol consumption, all associations remained significant.
“Our findings suggest that the rs738409 G allele may predispose patients to fat accumulation in the liver, but that other factors, environmental or hereditary, may be required for the development of inflammation, cellular injury and fibrosis,” says study leader T. Jake Liang, M.D. “However, once patients develop NASH, the rs738409 G allele predisposes them to more severe injury.”
NAFLD is becoming increasingly prevalent in pediatric patients, prompting the researchers to also search for an association between the PNPLA3 SNPs and disease severity in 223 children enrolled in the same study groups as the adults. While no association was found, the presence of the rs738409 G allele was associated with a younger age at the time of liver biopsy, suggesting a younger age of disease presentation.
Concurrent research at Massachusetts General Hospital also identified the G allele of rs738409 in PNPLA3 as a potential risk factor for NAFLD. The Mass General team examined SNPs at 7 loci associated with steatosis in 592 patients of European ancestry from the CRN and 1,405 ancestry-matched controls from the MIGen study. No association was observed between rs738409 G and BMI, triglyceride levels, and high and low-density lipoprotein levels, or diabetes. None of the variants at the other six other loci were associated with NAFLD.
The results suggest that certain inherited variations in lipid metabolism precede and could lead to the development of liver disease. The analysis indicates that genetic variation at PNPLA3 confers a markedly increased risk of severe histological features of NAFLD, without a strong effect on metabolic syndrome component traits. Given that PNPLA3 appears to be part of a family of enzymes that affect lipid metabolism, this suggests that altering lipid metabolism, particularly within the liver, can affect accumulation of fat and subsequent development of NAFLD.
Study leader Elizabeth Speliotes, M.D., Ph.D., M.Ph., concludes, “Through genetic analyses, we may be able to delineate the causal pathways that lead to specific disease complications of metabolic risk factors such as NAFLD and, in the future, selectively target them for therapeutic intervention.”
Full bibliographic information
Article: “PNPLA3 Variants Specifically Confer Increased Risk for Histologic NAFLD but Not Metabolic Disease.” Elizabeth K. Speliotes, Johannah L. Butler, Cameron Palmer, Benjamin F. Voight, the GIANT Consortium, the MIGen Consortium, the NASH CRN, Joel N. Hirschhorn. Hepatology; Published Online: May 18, 2010 (DOI: 10.1002/hep.23768); Print Issue Date: September 2010. http://onlinelibrary.wiley.com/doi/10.1002/hep.23768/abstract
Article: “The Association of Genetic Variability in PNPLA3 with Histological Severity of Non-Alcoholic Fatty Liver Disease.” Yaron Rotman, Christopher Koh, Joseph M. Zmuda, David E. Kleiner, T. Jake Liang, and the NASH CRN. Hepatology; Published Online: May 14, 2010 (DOI: 10.1002/hep.23759); Print Issue Date: September 2010. http://onlinelibrary.wiley.com/doi/10.1002/hep.23759/abstract
Source
Risk factors for infection during treatment with peginterferon ALFA and ribavirin for chronic hepatitis C
Robert Roomer 1, Bettina E. Hansen 1,2, Harry L.A. Janssen 1, Robert J. de Knegt 1,*,†
DOI: 10.1002/hep.23842
Copyright © 2010 American Association for the Study of Liver Diseases
Author Information
1 Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
2 Department of Biostatistics, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
Email: Robert J. de Knegt (r.roomer@erasmusmc.nl)
*Correspondence: Robert J. de Knegt, Department Gastrenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Room Ca-415's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands
†Ph: 0031 10 7031617
Publication History
Accepted manuscript online: 29 JUL 2010 12:00AM EST
Manuscript Accepted: 6 JUL 2010
Manuscript Revised: 24 JUN 2010
Manuscript Received: 28 APR 2010
Keywords:
Dose reductions;neutropenia;cirrhosis;HCV;age
Abstract
Neutropenia during treatment with peginterferon alfa and ribavirin for chronic hepatitis C (HCV) is a common cause for dose reductions of peginterferon alfa. These reductions are performed to prevent bacterial and fungal infections, which are common during HCV treatment and attributed to neutropenia. The aims of this study were to investigate the occurrence of infections and their relation to neutropenia and to find potential risk factors for infections during HCV treatment.
In this single center cohort study 2876 visits of 321 patients treated with peginterferon alfa and ribavirin were evaluated for neutropenia, infections, dose reductions and potential risk factors for infection during HCV treatment.
Baseline mean absolute neutrophil count (ANC) was 3420 cells/μL, 16 patients had baseline ANC below 1500 cells/μL. During treatment neutropenia defined as ANC <750 cells/μL was observed in 95 patients (29.7%) and ANC < 375/μL was observed in 16 patients (5%). Ninety-six infections were observed in 70 patients (21.8%). Thirteen infections (13.5%) were defined as severe. Infections were not correlated with neutropenia during treatment. Dose reductions did not lead to a decrease in infection rate. In the multivariate logistic regression analysis age older than 55 (OR 2.06, CI 1.19-3.56, p=0.01) and baseline hyperglycemia (OR 2.17 95% CI 1.15-4.10, p=0.016) were associated with an increased risk of infection during HCV treatment. Cirrhosis and chronic obstructive pulmonary disease (COPD) were no risk factors for infections.
Conclusion:
Bacterial infections during treatment with peginterferon alfa and ribavirin are not associated with neutropenia. Older patients and patients with poorly controlled diabetes mellitus are more at risk to develop infections during HCV treatment. (HEPATOLOGY 2010.)
Source
DOI: 10.1002/hep.23842
Copyright © 2010 American Association for the Study of Liver Diseases
Author Information
1 Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
2 Department of Biostatistics, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
Email: Robert J. de Knegt (r.roomer@erasmusmc.nl)
*Correspondence: Robert J. de Knegt, Department Gastrenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Room Ca-415's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands
†Ph: 0031 10 7031617
Publication History
Accepted manuscript online: 29 JUL 2010 12:00AM EST
Manuscript Accepted: 6 JUL 2010
Manuscript Revised: 24 JUN 2010
Manuscript Received: 28 APR 2010
Keywords:
Dose reductions;neutropenia;cirrhosis;HCV;age
Abstract
Neutropenia during treatment with peginterferon alfa and ribavirin for chronic hepatitis C (HCV) is a common cause for dose reductions of peginterferon alfa. These reductions are performed to prevent bacterial and fungal infections, which are common during HCV treatment and attributed to neutropenia. The aims of this study were to investigate the occurrence of infections and their relation to neutropenia and to find potential risk factors for infections during HCV treatment.
In this single center cohort study 2876 visits of 321 patients treated with peginterferon alfa and ribavirin were evaluated for neutropenia, infections, dose reductions and potential risk factors for infection during HCV treatment.
Baseline mean absolute neutrophil count (ANC) was 3420 cells/μL, 16 patients had baseline ANC below 1500 cells/μL. During treatment neutropenia defined as ANC <750 cells/μL was observed in 95 patients (29.7%) and ANC < 375/μL was observed in 16 patients (5%). Ninety-six infections were observed in 70 patients (21.8%). Thirteen infections (13.5%) were defined as severe. Infections were not correlated with neutropenia during treatment. Dose reductions did not lead to a decrease in infection rate. In the multivariate logistic regression analysis age older than 55 (OR 2.06, CI 1.19-3.56, p=0.01) and baseline hyperglycemia (OR 2.17 95% CI 1.15-4.10, p=0.016) were associated with an increased risk of infection during HCV treatment. Cirrhosis and chronic obstructive pulmonary disease (COPD) were no risk factors for infections.
Conclusion:
Bacterial infections during treatment with peginterferon alfa and ribavirin are not associated with neutropenia. Older patients and patients with poorly controlled diabetes mellitus are more at risk to develop infections during HCV treatment. (HEPATOLOGY 2010.)
Source
Beta-blockers in cirrhosis: Friend and foe?†
Florence Wong 1,*,‡, Francesco Salerno 2
DOI: 10.1002/hep.23852
Copyright © 2010 American Association for the Study of Liver Diseases
Author Information
1 Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
2 The Policlinico IRCCS San Donato and Dipartimento di Scienze Medico-Chirurgiche, Università di Milano, Italy
Email: Florence Wong (florence.wong@utoronto.ca)
*Correspondence: Florence Wong, 9N/983, Toronto General Hospital, University of Toronto, 200 Elizabeth Street, Toronto, Ontario M5G2C4, Canada
†There is no financial support for this article
‡Ph: 416-340 3834; Fax: 416-340 5019
Publication History
Accepted manuscript online: 29 JUL 2010 12:00AM EST
Manuscript Accepted: 8 JUL 2010
Manuscript Received: 29 JUN 2010
Keywords:
propranolol;non-selective beta-blockers;cirrhosis;refractory ascites;sepsis;variceal bleed
Abstract
Patients with cirrhosis are at risk for developing complications that can negatively impact their survival (1). These complications include the development of hepatocellular carcinoma (HCC), sepsis, renal failure and gastrointestinal bleeding, mainly variceal. The risk of bleeding is mainly related to the development of varices from portal hypertension. Bleeding from varices, whether esophageal or gastric, is associated with a mortality risk of 40% at 1 year (2).
Twenty-nine years ago, a randomized controlled trial (RCT) from France involving 74 patients with cirrhosis with a history of gastrointestinal bleeding showed that propranolol, a non-selective beta-blocker (NSBB), significantly reduced the risk of re-bleeding from esophageal varices (3). Since then, 615 papers have been published in the English literature on the use of propranolol or nadolol (the other NSBB) in cirrhosis, both for primary and secondary prophylaxis. In fact, NSBBs have become one of the most effective preventative therapies in patients with cirrhosis (4). The advantage of using NSBBs, however, must be weighed against the risks associated with their chronic use. NSBBs are contraindicated in patients with refractory asthma, respiratory failure, advanced atrio-ventricular block and severe arterial hypotension. In order to improve the risk/benefit ratio, administration of beta blockers is recommended only in patients with a substantial risk of bleeding such as those patients with medium or large varices or patients with small esophageal varices who are Child-Pugh class C (5,6). If possible, hepatic venous pressure gradient (HVPG) should be measured before and 1-2 months after NSBB administration to identify responders (those with a final HVPG <12mmHg or those who show a decrease of ≥20% in HVPG versus the pre-treatment value) who are most likely to benefit from NSBB prophylaxis. Non-responders should discontinue therapy so to prevent the development of side effects when their chances of any therapeutic benefits are small (7). (HEPATOLOGY 2010.)
Source
DOI: 10.1002/hep.23852
Copyright © 2010 American Association for the Study of Liver Diseases
Author Information
1 Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
2 The Policlinico IRCCS San Donato and Dipartimento di Scienze Medico-Chirurgiche, Università di Milano, Italy
Email: Florence Wong (florence.wong@utoronto.ca)
*Correspondence: Florence Wong, 9N/983, Toronto General Hospital, University of Toronto, 200 Elizabeth Street, Toronto, Ontario M5G2C4, Canada
†There is no financial support for this article
‡Ph: 416-340 3834; Fax: 416-340 5019
Publication History
Accepted manuscript online: 29 JUL 2010 12:00AM EST
Manuscript Accepted: 8 JUL 2010
Manuscript Received: 29 JUN 2010
Keywords:
propranolol;non-selective beta-blockers;cirrhosis;refractory ascites;sepsis;variceal bleed
Abstract
Patients with cirrhosis are at risk for developing complications that can negatively impact their survival (1). These complications include the development of hepatocellular carcinoma (HCC), sepsis, renal failure and gastrointestinal bleeding, mainly variceal. The risk of bleeding is mainly related to the development of varices from portal hypertension. Bleeding from varices, whether esophageal or gastric, is associated with a mortality risk of 40% at 1 year (2).
Twenty-nine years ago, a randomized controlled trial (RCT) from France involving 74 patients with cirrhosis with a history of gastrointestinal bleeding showed that propranolol, a non-selective beta-blocker (NSBB), significantly reduced the risk of re-bleeding from esophageal varices (3). Since then, 615 papers have been published in the English literature on the use of propranolol or nadolol (the other NSBB) in cirrhosis, both for primary and secondary prophylaxis. In fact, NSBBs have become one of the most effective preventative therapies in patients with cirrhosis (4). The advantage of using NSBBs, however, must be weighed against the risks associated with their chronic use. NSBBs are contraindicated in patients with refractory asthma, respiratory failure, advanced atrio-ventricular block and severe arterial hypotension. In order to improve the risk/benefit ratio, administration of beta blockers is recommended only in patients with a substantial risk of bleeding such as those patients with medium or large varices or patients with small esophageal varices who are Child-Pugh class C (5,6). If possible, hepatic venous pressure gradient (HVPG) should be measured before and 1-2 months after NSBB administration to identify responders (those with a final HVPG <12mmHg or those who show a decrease of ≥20% in HVPG versus the pre-treatment value) who are most likely to benefit from NSBB prophylaxis. Non-responders should discontinue therapy so to prevent the development of side effects when their chances of any therapeutic benefits are small (7). (HEPATOLOGY 2010.)
Source
Quality of Care in Patients With Chronic Hepatitis C Virus Infection
IMPROVING PATIENT CARE
A Cohort Study
Fasiha Kanwal, MD, MSHS; Mark S. Schnitzler, PhD; Bruce R. Bacon, MD; Tuyen Hoang, PhD; Paula M. Buchanan, PhD; and Steven M. Asch, MD, MPH
+ Author Affiliations
Abstract
Background: Medicare has proposed quality-of-care indicators for chronic hepatitis C virus (HCV) infection. The extent to which these standards are met in practice is largely unknown.
Objective: To evaluate the quality of health care that patients with HCV receive and the factors associated with receipt of quality care.
Design: Retrospective cohort study.
Setting: Nationwide U.S. health insurance company research database.
Participants: 10 385 patients with HCV enrolled in the database between 2003 and 2006. Patients were included if they were eligible for at least 1 quality indicator.
Measurements: Quality of HCV care received by patients, as measured by 7 explicit quality indicators included in Medicare's 2009 Physician Quality Reporting Initiative.
Results: Proportions of patients meeting quality indicators varied, ranging from 21.5% for vaccination to 79% for the HCV genotype testing indicator. Overall, 18.5% of patients (95% CI, 18% to 19%) received all recommended care. Older age and presence of comorbid conditions were associated with lower quality, whereas elevated liver enzyme levels, cirrhosis, and HIV infection were associated with higher quality. Patients who saw both generalists and specialists received the best care (odds ratio of receiving care for which a patient is eligible: specialists alone, 0.79 [CI, 0.66 to 0.95]; primary care physician alone, 0.44 [CI, 0.40 to 0.48]).
Limitations: The study had an observational retrospective design, used a convenience sample, and had no information on patient ethnicity. It may be that the indicators or the reporting of the indicators of HCV care—and not the care itself—is suboptimum.
Conclusion: Health care quality, based on Medicare criteria, is suboptimum for HCV. Care that included both specialists and generalists is associated with the best quality. Our results support the development of specialist and primary care collaboration to improve the quality of HCV care.
Primary Funding Source: Saint Louis University Liver Center.
Article and Author Information
Disclaimer: The opinions and assertions contained herein are the sole views of the authors and are not to be construed as official or as reflecting the views of the Department of Veterans Affairs.
Grant Support: Dr. Kanwal is supported by Veterans Affairs Health Services Research and Development Service Investigator Initiated Research Award IIR-07-111. This study was supported by an intramural grant from the Saint Louis University Liver Center.
Potential Conflicts of Interest: Dr. Kanwal: Grants received: Saint Louis University Liver Center. Dr. Bacon: Consultancies: Merck/Schering-Plough, Valeant. Honoraria: Merck/Schering-Plough, Gilead Sciences, Three Rivers Pharma, Vertex, Human Genome Sciences. Royalties: UpToDate. Dr. Bacon has also received payment for development of educational presentations, including service on speakers' bureaus, and has had his travel/accommodations expenses covered or reimbursed. Dr. Buchanan: Grants received (money to institution): Veterans Affairs Health Services Research and Development Service, Saint Louis University Liver Center. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M09-2380.
Reproducible Research Statement: Study protocol: Available from Dr. Kanwal (e-mail, fasiha.kanwal@va.gov). Statistical code: Available from Dr. Kanwal (e-mail, fasiha.kanwal@va.gov), Dr. Schnitzler (e-mail, schnitm@slu.edu), or Dr. Buchanan (e-mail, pbuchan1@slu.edu). Data set: Not available. These or similar data are available from commercial health insurance companies in the United States.
Requests for Single Reprints: Fasiha Kanwal, MD, MSHS, John Cochran Veterans Affairs Medical Center, 915 North Grand Boulevard, 111 JC/GI, St. Louis, MO 63106; e-mail, fasiha.kanwal@va.gov.
Current Author Addresses: Dr. Kanwal: John Cochran Veterans Affairs Medical Center, 915 North Grand Boulevard, 111 JC/GI, St. Louis, MO 63106.
Drs. Schnitzler and Buchanan: Center for Outcomes Research, Saint Louis University School of Medicine, 3545 Lafayette Avenue, St. Louis, MO 63104.
Dr. Bacon: Saint Louis University School of Medicine, Department of Internal Medicine, Division of Gastroenterology & Hepatology, 3635 Vista Avenue at Grand Boulevard, St. Louis, MO 63110-0250.
Drs. Hoang and Asch: Department of Internal Medicine and Health Services Research, Veterans Affairs Greater Los Angeles Medical Center, 11301 Wilshire Boulevard, Building 500 (111-G), Los Angeles, CA 90073.
Author Contributions: Conception and design: F. Kanwal, M.S. Schnitzler, S.M. Asch.
Analysis and interpretation of the data: F. Kanwal, M.S. Schnitzler, T. Hoang, P.M. Buchanan, S.M. Asch.
Drafting of the article: F. Kanwal, M.S. Schnitzler, P.M. Buchanan, S.M. Asch.
Critical revision of the article for important intellectual content: F. Kanwal, M.S. Schnitzler, B.R. Bacon, S.M. Asch.
Final approval of the article: M.S. Schnitzler, B.R. Bacon, P.M. Buchanan, S.M. Asch.
Provision of study materials or patients: M.S. Schnitzler.
Statistical expertise: M.S. Schnitzler, T. Hoang, P.M. Buchanan.
Obtaining of funding: F. Kanwal, M.S. Schnitzler.
Administrative, technical, or logistic support: F. Kanwal, B.R. Bacon.
Collection and assembly of data: M.S. Schnitzler, P.M. Buchanan.
Source
A Cohort Study
Fasiha Kanwal, MD, MSHS; Mark S. Schnitzler, PhD; Bruce R. Bacon, MD; Tuyen Hoang, PhD; Paula M. Buchanan, PhD; and Steven M. Asch, MD, MPH
+ Author Affiliations
Abstract
Background: Medicare has proposed quality-of-care indicators for chronic hepatitis C virus (HCV) infection. The extent to which these standards are met in practice is largely unknown.
Objective: To evaluate the quality of health care that patients with HCV receive and the factors associated with receipt of quality care.
Design: Retrospective cohort study.
Setting: Nationwide U.S. health insurance company research database.
Participants: 10 385 patients with HCV enrolled in the database between 2003 and 2006. Patients were included if they were eligible for at least 1 quality indicator.
Measurements: Quality of HCV care received by patients, as measured by 7 explicit quality indicators included in Medicare's 2009 Physician Quality Reporting Initiative.
Results: Proportions of patients meeting quality indicators varied, ranging from 21.5% for vaccination to 79% for the HCV genotype testing indicator. Overall, 18.5% of patients (95% CI, 18% to 19%) received all recommended care. Older age and presence of comorbid conditions were associated with lower quality, whereas elevated liver enzyme levels, cirrhosis, and HIV infection were associated with higher quality. Patients who saw both generalists and specialists received the best care (odds ratio of receiving care for which a patient is eligible: specialists alone, 0.79 [CI, 0.66 to 0.95]; primary care physician alone, 0.44 [CI, 0.40 to 0.48]).
Limitations: The study had an observational retrospective design, used a convenience sample, and had no information on patient ethnicity. It may be that the indicators or the reporting of the indicators of HCV care—and not the care itself—is suboptimum.
Conclusion: Health care quality, based on Medicare criteria, is suboptimum for HCV. Care that included both specialists and generalists is associated with the best quality. Our results support the development of specialist and primary care collaboration to improve the quality of HCV care.
Primary Funding Source: Saint Louis University Liver Center.
Article and Author Information
Disclaimer: The opinions and assertions contained herein are the sole views of the authors and are not to be construed as official or as reflecting the views of the Department of Veterans Affairs.
Grant Support: Dr. Kanwal is supported by Veterans Affairs Health Services Research and Development Service Investigator Initiated Research Award IIR-07-111. This study was supported by an intramural grant from the Saint Louis University Liver Center.
Potential Conflicts of Interest: Dr. Kanwal: Grants received: Saint Louis University Liver Center. Dr. Bacon: Consultancies: Merck/Schering-Plough, Valeant. Honoraria: Merck/Schering-Plough, Gilead Sciences, Three Rivers Pharma, Vertex, Human Genome Sciences. Royalties: UpToDate. Dr. Bacon has also received payment for development of educational presentations, including service on speakers' bureaus, and has had his travel/accommodations expenses covered or reimbursed. Dr. Buchanan: Grants received (money to institution): Veterans Affairs Health Services Research and Development Service, Saint Louis University Liver Center. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M09-2380.
Reproducible Research Statement: Study protocol: Available from Dr. Kanwal (e-mail, fasiha.kanwal@va.gov). Statistical code: Available from Dr. Kanwal (e-mail, fasiha.kanwal@va.gov), Dr. Schnitzler (e-mail, schnitm@slu.edu), or Dr. Buchanan (e-mail, pbuchan1@slu.edu). Data set: Not available. These or similar data are available from commercial health insurance companies in the United States.
Requests for Single Reprints: Fasiha Kanwal, MD, MSHS, John Cochran Veterans Affairs Medical Center, 915 North Grand Boulevard, 111 JC/GI, St. Louis, MO 63106; e-mail, fasiha.kanwal@va.gov.
Current Author Addresses: Dr. Kanwal: John Cochran Veterans Affairs Medical Center, 915 North Grand Boulevard, 111 JC/GI, St. Louis, MO 63106.
Drs. Schnitzler and Buchanan: Center for Outcomes Research, Saint Louis University School of Medicine, 3545 Lafayette Avenue, St. Louis, MO 63104.
Dr. Bacon: Saint Louis University School of Medicine, Department of Internal Medicine, Division of Gastroenterology & Hepatology, 3635 Vista Avenue at Grand Boulevard, St. Louis, MO 63110-0250.
Drs. Hoang and Asch: Department of Internal Medicine and Health Services Research, Veterans Affairs Greater Los Angeles Medical Center, 11301 Wilshire Boulevard, Building 500 (111-G), Los Angeles, CA 90073.
Author Contributions: Conception and design: F. Kanwal, M.S. Schnitzler, S.M. Asch.
Analysis and interpretation of the data: F. Kanwal, M.S. Schnitzler, T. Hoang, P.M. Buchanan, S.M. Asch.
Drafting of the article: F. Kanwal, M.S. Schnitzler, P.M. Buchanan, S.M. Asch.
Critical revision of the article for important intellectual content: F. Kanwal, M.S. Schnitzler, B.R. Bacon, S.M. Asch.
Final approval of the article: M.S. Schnitzler, B.R. Bacon, P.M. Buchanan, S.M. Asch.
Provision of study materials or patients: M.S. Schnitzler.
Statistical expertise: M.S. Schnitzler, T. Hoang, P.M. Buchanan.
Obtaining of funding: F. Kanwal, M.S. Schnitzler.
Administrative, technical, or logistic support: F. Kanwal, B.R. Bacon.
Collection and assembly of data: M.S. Schnitzler, P.M. Buchanan.
Source
Visceral adiposity index is associated with histological findings and with high viral load in patients with chronic hepatitis C due to genotype 1†
Salvatore Petta 1,*,‡, Marco Amato 2, Daniela Cabibi 3, Calogero Cammà 1, Vito Di Marco 1, Carla Giordano 2, Aldo Galluzzo 2, Antonio Craxì 1
DOI: 10.1002/hep.23859
Copyright © 2010 American Association for the Study of Liver Diseases
Author Information
1 Cattedra di Gastroenterologia, DiBiMIS, University of Palermo, Italy
2 Dipartimento di Oncologia Sperimentale ed Applicazioni Cliniche (DOSAC), Section of Endocrinology, University of Palermo, Italy
3 Cattedra di Anatomia Patologica, University of Palermo, Italy
Email: Salvatore Petta (petsa@inwind.it)
*Correspondence: Salvatore Petta, Gastroenterologia & Epatologia, Piazza delle Cliniche, 2, 90127 Palermo, Italy
†FINANCIAL SUPPORT No conflict of interest exists.
‡Ph: +39 091 655 2145; Fax +39 091 655 2156
Publication History
Accepted manuscript online: 29 JUL 2010 12:00AM EST
Manuscript Accepted: 13 JUL 2010
Manuscript Revised: 9 JUL 2010
Manuscript Received: 20 MAY 2010
Abstract
Background and Aims:
Metabolic factors have been associated with liver damage in patients with genotype 1 chronic hepatitis C (G1 CHC). We tested visceral adiposity index (VAI), a new marker of adipose dysfunction in G1 CHC patients to assess its association with host and viral factors, and its link to both histological findings and sustained virologic response (SVR).
Materials and Methods:
Two hundred thirty-six consecutive G1 CHC patients were evaluated by liver biopsy and anthropometric and metabolic measurements, including IR, the homeostasis model assessment (HOMA), and VAI by using waist circumference, body mass index, triglycerides and HDL. All biopsies were scored by one pathologist for staging and grading (Scheuer), and graded for steatosis, which was considered moderate-severe if ≥30%.
Results:
VAI score was independently associated with higher HOMA score (p=0.009), higher Log10 HCV RNA levels (p=0.01), necroinflammatory activity (p=0.04), and steatosis (p=0.04), by multiple linear regression analysis. IR (OR 3.879,95%CI 1.727–8.713, p=0.001), higher VAI score (OR 1.472,95%CI 1.051–2.062, p=0.02), and fibrosis (OR 2.255,95%CI 1.349–3.768, p=0.002) were linked to steatosis ≥30% by multiple logistic regression analysis. Older age (OR 1.030;95% CI 1.002-1.059; p=0.03), high VAI score (OR 1.618;95%CI 1.001-2.617; p=0.04) and fibrosis (OR 2.608;95%CI 1.565-4.345; p<0.001) were independently associated with moderate-severe necroinflammatory activity by logistic regression analysis. No independent associations were found between VAI score and both fibrosis and SVR.
Conclusion:
In G1 CHC patients, higher VAI score, a new index of adipose dysfunction, is independently associated with both steatosis and necroinflammatory activity, and has a direct correlation with viral load. (HEPATOLOGY 2010.)
Source
DOI: 10.1002/hep.23859
Copyright © 2010 American Association for the Study of Liver Diseases
Author Information
1 Cattedra di Gastroenterologia, DiBiMIS, University of Palermo, Italy
2 Dipartimento di Oncologia Sperimentale ed Applicazioni Cliniche (DOSAC), Section of Endocrinology, University of Palermo, Italy
3 Cattedra di Anatomia Patologica, University of Palermo, Italy
Email: Salvatore Petta (petsa@inwind.it)
*Correspondence: Salvatore Petta, Gastroenterologia & Epatologia, Piazza delle Cliniche, 2, 90127 Palermo, Italy
†FINANCIAL SUPPORT No conflict of interest exists.
‡Ph: +39 091 655 2145; Fax +39 091 655 2156
Publication History
Accepted manuscript online: 29 JUL 2010 12:00AM EST
Manuscript Accepted: 13 JUL 2010
Manuscript Revised: 9 JUL 2010
Manuscript Received: 20 MAY 2010
Abstract
Background and Aims:
Metabolic factors have been associated with liver damage in patients with genotype 1 chronic hepatitis C (G1 CHC). We tested visceral adiposity index (VAI), a new marker of adipose dysfunction in G1 CHC patients to assess its association with host and viral factors, and its link to both histological findings and sustained virologic response (SVR).
Materials and Methods:
Two hundred thirty-six consecutive G1 CHC patients were evaluated by liver biopsy and anthropometric and metabolic measurements, including IR, the homeostasis model assessment (HOMA), and VAI by using waist circumference, body mass index, triglycerides and HDL. All biopsies were scored by one pathologist for staging and grading (Scheuer), and graded for steatosis, which was considered moderate-severe if ≥30%.
Results:
VAI score was independently associated with higher HOMA score (p=0.009), higher Log10 HCV RNA levels (p=0.01), necroinflammatory activity (p=0.04), and steatosis (p=0.04), by multiple linear regression analysis. IR (OR 3.879,95%CI 1.727–8.713, p=0.001), higher VAI score (OR 1.472,95%CI 1.051–2.062, p=0.02), and fibrosis (OR 2.255,95%CI 1.349–3.768, p=0.002) were linked to steatosis ≥30% by multiple logistic regression analysis. Older age (OR 1.030;95% CI 1.002-1.059; p=0.03), high VAI score (OR 1.618;95%CI 1.001-2.617; p=0.04) and fibrosis (OR 2.608;95%CI 1.565-4.345; p<0.001) were independently associated with moderate-severe necroinflammatory activity by logistic regression analysis. No independent associations were found between VAI score and both fibrosis and SVR.
Conclusion:
In G1 CHC patients, higher VAI score, a new index of adipose dysfunction, is independently associated with both steatosis and necroinflammatory activity, and has a direct correlation with viral load. (HEPATOLOGY 2010.)
Source
Successful HCV eradication and inhibition of HIV replication by intravenous silibinin in an HIV–HCV coinfected patient
JOURNAL OF CLINICAL VIROLOGY
doi:10.1016/j.jcv.2010.07.006
© 2010 Elsevier B.V. All rights reserved.
B.A. Payer, T. Reiberger, K. Rutter, S. Beinhardt, A.F. Staettermayer, M. Peck-Radosavljevic, P. Ferenci
Received 12 May 2010; received in revised form 1 July 2010; accepted 6 July 2010. published online 16 August 2010.
Corrected Proof
Abstract
Introduction
The efficacy of antiviral therapy with pegylated interferon (PEGIFN) plus ribavirin (RBV) in patients with HIV and hepatitis C virus (HCV) coinfection is limited. Intravenous silibinin (ivSIL), a milk thistle extract with proven antiviral effects represents a novel therapeutic strategy for virological nonresponders.
Methods
We report a case of an HIV–HCV coinfected patient, who has not responded to a prior course of PEGIFN-α2a (180μg/week/s.c.) and RBV (1000mg/day/p.o.). Testing for IL-28β small nucleotid polymorphism revealed the nonfavourable genotype T/T. Antiretroviral therapy was not prescribed because the patients presented with well-preserved CD4+ cell counts and low HIV-RNA levels. She received retreatment with ivSIL for two weeks followed by PEGIFN/RBV combination therapy starting at week 1.
Results
After 2 weeks of ivSIL therapy both HCV-RNA and HIV-RNA become undetectable. On ivSIL monotherapy we noticed a trend towards an increase of CD4+ cell counts and a decrease of HIV-RNA. After 16 weeks PEGIFN+RBV was discontinued due to patients wish because of adverse events. HCV-RNA was still negative 24 weeks after cessation of therapy, while HIV-RNA returned to baseline levels.
Conclusion
ivSIL may represent a potential treatment option for retreatment of HIV–HCV coinfected patients nonresponding to PEGIFN+RBV combination therapy. Further investigations on the possible beneficial effects of ivSIL on CD4+ cell counts and HIV-RNA levels are necessary.
Keywords: HCV, HIV, Silibinin, Pegylated interferon, Ribavirin, Nonresponse
Source
doi:10.1016/j.jcv.2010.07.006
© 2010 Elsevier B.V. All rights reserved.
B.A. Payer, T. Reiberger, K. Rutter, S. Beinhardt, A.F. Staettermayer, M. Peck-Radosavljevic, P. Ferenci
Received 12 May 2010; received in revised form 1 July 2010; accepted 6 July 2010. published online 16 August 2010.
Corrected Proof
Abstract
Introduction
The efficacy of antiviral therapy with pegylated interferon (PEGIFN) plus ribavirin (RBV) in patients with HIV and hepatitis C virus (HCV) coinfection is limited. Intravenous silibinin (ivSIL), a milk thistle extract with proven antiviral effects represents a novel therapeutic strategy for virological nonresponders.
Methods
We report a case of an HIV–HCV coinfected patient, who has not responded to a prior course of PEGIFN-α2a (180μg/week/s.c.) and RBV (1000mg/day/p.o.). Testing for IL-28β small nucleotid polymorphism revealed the nonfavourable genotype T/T. Antiretroviral therapy was not prescribed because the patients presented with well-preserved CD4+ cell counts and low HIV-RNA levels. She received retreatment with ivSIL for two weeks followed by PEGIFN/RBV combination therapy starting at week 1.
Results
After 2 weeks of ivSIL therapy both HCV-RNA and HIV-RNA become undetectable. On ivSIL monotherapy we noticed a trend towards an increase of CD4+ cell counts and a decrease of HIV-RNA. After 16 weeks PEGIFN+RBV was discontinued due to patients wish because of adverse events. HCV-RNA was still negative 24 weeks after cessation of therapy, while HIV-RNA returned to baseline levels.
Conclusion
ivSIL may represent a potential treatment option for retreatment of HIV–HCV coinfected patients nonresponding to PEGIFN+RBV combination therapy. Further investigations on the possible beneficial effects of ivSIL on CD4+ cell counts and HIV-RNA levels are necessary.
Keywords: HCV, HIV, Silibinin, Pegylated interferon, Ribavirin, Nonresponse
Source
JBC Thematic Series Explores Hepatitis C Virus
BY NICK ZAGORSKI
The JBC recently unveiled a new thematic minireview series to showcase some of the recent advances in understanding the hepatitis C virus.
Hepatitis C virus is a member of the hepacivirus viral group and the causative agent of hepatitis C, an infectious disease affecting as many as 180 million people worldwide, and a major contributor to chronic liver diseases, including cirrhosis and hepatocellular carcinoma. Although much has been learned about how HCV replicates and how the virus is transmitted, it remains problematic from a therapeutic standpoint. Unlike the related HBV, there is no effective vaccine against HCV, and the present treatment for HCV infection, a regimen of pegylated interferon alpha and the antiviral drug ribavirin, shows varying success rates of 40–80 percent, depending on HCV genotype.
Recently, though, researchers have made significant advances in understanding HCV biochemistry, its life cycle and its interaction with hosts, which may lead to improved treatments and an effective vaccine. To showcase some of these important new findings, the Journal of Biological Chemistry recently presented a thematic review series titled “Hepatitis C Virus-host Interactions.”
This minireview series, coordinated by JBC Associate Editor Charles E. Samuel of the University of California, Santa Barbara, appeared in the May 10 issue of the journal and is collectively available online.
The series consists of five minireviews, two of which appeared in the JBC in previous years but provide an important foundation for the newer studies. The first is a 2006 review by Ralf Bartenschlager and colleagues titled “From Structure to Function: New Insights into Hepatitis C Virus RNA Replication.” The paper describes structural and biochemical insights into HCV RNA replication gained from HCV replicon systems and other methods allowing for efficient propagation of infectious HCV in tissue culture. The subsequent development of a cell-culture system that permitted the complete replication of HCV provided a tool to biochemically delineate the initial processes in infection, namely virion attachment and entry. These advances are described in the 2008 review by Thomas von Hahn and Charles M. Rice entitled “Hepatitis C Viral Entry.”
In the first of the three new minireviews, titled “Hepatitis C Virus Non-structural Protein 3 (HCV NS3): a Multifunctional Antiviral Target,” Craig E. Cameron and colleagues discuss new developments in the biochemistry and structural biology of the bifunctional NS3 protein, which possesses both serine protease activity (in the N-terminal region) and RNA helicase activity (in the C-terminal region). The second new minireview, written by Daniel M Jones and John McLauchlan and titled “Hepatitis C Virus: Assembly and Release of Virus Particles,” summarizes progress in understanding HCV protein trafficking and the various stages of virion assembly and release. The third and final minireview is by Stanley M. Lemon. Titled “Induction and Evasion of Innate Antiviral Responses to Hepatitis C Virus,” this article summarizes the progress in understanding the cellular signaling pathways and antiviral responses antagonized by HCV proteins and the multiple strategies utilized by HCV to evade activated innate antiviral responses.
Together, these five minireviews provide a comprehensive overview of the current state of HCV research and should be a valuable resource to all.
Nick Zagorski (nzagorski@asbmb.org) is a science writer at ASBMB.
Source
The JBC recently unveiled a new thematic minireview series to showcase some of the recent advances in understanding the hepatitis C virus.
Hepatitis C virus is a member of the hepacivirus viral group and the causative agent of hepatitis C, an infectious disease affecting as many as 180 million people worldwide, and a major contributor to chronic liver diseases, including cirrhosis and hepatocellular carcinoma. Although much has been learned about how HCV replicates and how the virus is transmitted, it remains problematic from a therapeutic standpoint. Unlike the related HBV, there is no effective vaccine against HCV, and the present treatment for HCV infection, a regimen of pegylated interferon alpha and the antiviral drug ribavirin, shows varying success rates of 40–80 percent, depending on HCV genotype.
Recently, though, researchers have made significant advances in understanding HCV biochemistry, its life cycle and its interaction with hosts, which may lead to improved treatments and an effective vaccine. To showcase some of these important new findings, the Journal of Biological Chemistry recently presented a thematic review series titled “Hepatitis C Virus-host Interactions.”
This minireview series, coordinated by JBC Associate Editor Charles E. Samuel of the University of California, Santa Barbara, appeared in the May 10 issue of the journal and is collectively available online.
The series consists of five minireviews, two of which appeared in the JBC in previous years but provide an important foundation for the newer studies. The first is a 2006 review by Ralf Bartenschlager and colleagues titled “From Structure to Function: New Insights into Hepatitis C Virus RNA Replication.” The paper describes structural and biochemical insights into HCV RNA replication gained from HCV replicon systems and other methods allowing for efficient propagation of infectious HCV in tissue culture. The subsequent development of a cell-culture system that permitted the complete replication of HCV provided a tool to biochemically delineate the initial processes in infection, namely virion attachment and entry. These advances are described in the 2008 review by Thomas von Hahn and Charles M. Rice entitled “Hepatitis C Viral Entry.”
In the first of the three new minireviews, titled “Hepatitis C Virus Non-structural Protein 3 (HCV NS3): a Multifunctional Antiviral Target,” Craig E. Cameron and colleagues discuss new developments in the biochemistry and structural biology of the bifunctional NS3 protein, which possesses both serine protease activity (in the N-terminal region) and RNA helicase activity (in the C-terminal region). The second new minireview, written by Daniel M Jones and John McLauchlan and titled “Hepatitis C Virus: Assembly and Release of Virus Particles,” summarizes progress in understanding HCV protein trafficking and the various stages of virion assembly and release. The third and final minireview is by Stanley M. Lemon. Titled “Induction and Evasion of Innate Antiviral Responses to Hepatitis C Virus,” this article summarizes the progress in understanding the cellular signaling pathways and antiviral responses antagonized by HCV proteins and the multiple strategies utilized by HCV to evade activated innate antiviral responses.
Together, these five minireviews provide a comprehensive overview of the current state of HCV research and should be a valuable resource to all.
Nick Zagorski (nzagorski@asbmb.org) is a science writer at ASBMB.
Source
Impact of diabetes mellitus on incidence of hepatocellular carcinoma in chronic hepatitis C patients treated with interferon-based antiviral therapy
International Journal of Cancer
DOI: 10.1002/ijc.25585
Copyright © 2010 UICC
Author Information
Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan
Email: Sheng-Nan Lu M.D., M.P.H., Ph.D. (juten@ms17.hinet.net)
*Correspondence: Sheng-Nan Lu M.D., M.P.H., Ph.D., Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital. 123 Ta Pei Road, Niao Sung 833 Kaohsiung, Taiwan
†Ph: 886-7-7317123 ext. 8301; Fax: 886-7-7322402
Publication History
Accepted manuscript online: 28 JUL 2010 12:00AM EST
Manuscript Accepted: 13 JUL 2010
Manuscript Revised: 22 JUN 2010
Manuscript Received: 30 MAR 2010
Funded by
Chang Gung Memorial Hospital, Taiwan. Grant Number: CMRPG880241
Keywords:
hepatitis C virus;diabetes mellitus;interferon;hepatocellular carcinoma;survival
Abstract
There is strong evidence linking chronic hepatitis C virus (HCV) infection and type 2 diabetes mellitus (DM). Recent studies have suggested that DM is associated with increased risk of developing hepatocellular carcinoma (HCC). The aim of this cohort study was to assess whether DM influence the incidence of HCC in chronic hepatitis C patients treated with interferon (IFN)-based antiviral therapy. A total of 1,470 chronic hepatitis C patients treated with IFN or pegylated-IFN plus ribavirin therapy were enrolled. Of them, 253 (17%) patients had DM at entry. Evaluation of HCC incidence was performed by Kaplan-Meier method and Cox proportional hazards analysis. Patients with baseline DM were significantly older and had higher body mass index, serum transaminase levels and fibrosis scores and lower platelet counts compared with non-DM subjects. Sustained virological response (SVR) was achieved in 160 (63%) of DM and 867 (71%) of non-DM patients (P=0.008). During a median follow-up period of 4.3 years, HCC developed in 21 (8.3%) of DM and 66 (5.4%) of non-DM patients (P=0.017). However, DM was not an independent covariate by Cox proportional hazards analysis. In a subgroup analysis, DM (hazard ratio, 4.32; 95% confidence interval, 1.23-15.25; P=0.023) was an independent predictor of HCC in the SVR patients without baseline cirrhosis, despite a low HCC incidence. In conclusion, DM has a selective impact on HCC development among chronic hepatitis C patients after IFN-based therapy. DM may increase the HCC risk in chronic hepatitis C without cirrhosis after eradication of HCV.
Source
DOI: 10.1002/ijc.25585
Copyright © 2010 UICC
Author Information
Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan
Email: Sheng-Nan Lu M.D., M.P.H., Ph.D. (juten@ms17.hinet.net)
*Correspondence: Sheng-Nan Lu M.D., M.P.H., Ph.D., Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital. 123 Ta Pei Road, Niao Sung 833 Kaohsiung, Taiwan
†Ph: 886-7-7317123 ext. 8301; Fax: 886-7-7322402
Publication History
Accepted manuscript online: 28 JUL 2010 12:00AM EST
Manuscript Accepted: 13 JUL 2010
Manuscript Revised: 22 JUN 2010
Manuscript Received: 30 MAR 2010
Funded by
Chang Gung Memorial Hospital, Taiwan. Grant Number: CMRPG880241
Keywords:
hepatitis C virus;diabetes mellitus;interferon;hepatocellular carcinoma;survival
Abstract
There is strong evidence linking chronic hepatitis C virus (HCV) infection and type 2 diabetes mellitus (DM). Recent studies have suggested that DM is associated with increased risk of developing hepatocellular carcinoma (HCC). The aim of this cohort study was to assess whether DM influence the incidence of HCC in chronic hepatitis C patients treated with interferon (IFN)-based antiviral therapy. A total of 1,470 chronic hepatitis C patients treated with IFN or pegylated-IFN plus ribavirin therapy were enrolled. Of them, 253 (17%) patients had DM at entry. Evaluation of HCC incidence was performed by Kaplan-Meier method and Cox proportional hazards analysis. Patients with baseline DM were significantly older and had higher body mass index, serum transaminase levels and fibrosis scores and lower platelet counts compared with non-DM subjects. Sustained virological response (SVR) was achieved in 160 (63%) of DM and 867 (71%) of non-DM patients (P=0.008). During a median follow-up period of 4.3 years, HCC developed in 21 (8.3%) of DM and 66 (5.4%) of non-DM patients (P=0.017). However, DM was not an independent covariate by Cox proportional hazards analysis. In a subgroup analysis, DM (hazard ratio, 4.32; 95% confidence interval, 1.23-15.25; P=0.023) was an independent predictor of HCC in the SVR patients without baseline cirrhosis, despite a low HCC incidence. In conclusion, DM has a selective impact on HCC development among chronic hepatitis C patients after IFN-based therapy. DM may increase the HCC risk in chronic hepatitis C without cirrhosis after eradication of HCV.
Source
Bioelectrical impedance analysis in clinical practice: implications for hepatitis C therapy
Body composition analysis using phase angle (PA), determined by bioelectrical impedance analysis (BIA), reflects tissue electrical properties and has prognostic value in liver cirrhosis. Objective of this prospective study was to investigate clinical use and prognostic value of BIA-derived phase angle and alterations in body composition for hepatitis C infection (HCV) following antiviral therapy.
Methods: 37 consecutive patients with HCV infection were enrolled, BIA was performed and PA was calculated from each pair of measurements. 22 HCV genotype 3 patients treated for 24 weeks and 15 genotype 1 patients treated for 48 weeks, were examined before and after antiviral treatment and compared to 10 untreated HCV patients at 0, 24, and 48weeks.
Basic laboratory data were correlated to body composition alterations.
Results: Significant reduction in body fat (BF: 24.2+/-6.7kg vs.
19.9+/-6.6kg genotype1; 15.4+/-10.9kg vs. 13.2+/-12.1kg genotype3) and body cell mass (BCM: 27.3+/-6.8kg vs.
24.3+/-7.2kg genotype1; 27.7+/-8.8kg vs. 24.6+/-7.6kg genotype3) was found following treatment.
PA in genotype 3 patients was significantly lowered after antiviral treatment compared to initial measurements (5.9+/-0.7degrees vs. 5.4+/-0.8degrees).
Total body water (TBW) was significantly decreased in treated patients with genotype 1 (41.4+/-7.9l vs. 40.8+/-9.5l).
PA reduction was accompanied by flu-like syndromes, whereas TBW decline was more frequently associated with fatigue and cephalgia. Discussion: BIA offers a sophisticated analysis of body composition including BF, BCM and TBW for HCV patients following antiviral regimens.
PA reduction was associated with increased adverse effects of the antiviral therapy allowing a more dynamic therapy application.
Author: Alisan KahramanJohannes HilsenbeckMonika NygaJudith ErtleAlexander WreeMathias PlauthGuido GerkenAli Canbay
Credits/Source: Virology Journal 2010, 7:191
Published on: 2010-08-16
Source
Methods: 37 consecutive patients with HCV infection were enrolled, BIA was performed and PA was calculated from each pair of measurements. 22 HCV genotype 3 patients treated for 24 weeks and 15 genotype 1 patients treated for 48 weeks, were examined before and after antiviral treatment and compared to 10 untreated HCV patients at 0, 24, and 48weeks.
Basic laboratory data were correlated to body composition alterations.
Results: Significant reduction in body fat (BF: 24.2+/-6.7kg vs.
19.9+/-6.6kg genotype1; 15.4+/-10.9kg vs. 13.2+/-12.1kg genotype3) and body cell mass (BCM: 27.3+/-6.8kg vs.
24.3+/-7.2kg genotype1; 27.7+/-8.8kg vs. 24.6+/-7.6kg genotype3) was found following treatment.
PA in genotype 3 patients was significantly lowered after antiviral treatment compared to initial measurements (5.9+/-0.7degrees vs. 5.4+/-0.8degrees).
Total body water (TBW) was significantly decreased in treated patients with genotype 1 (41.4+/-7.9l vs. 40.8+/-9.5l).
PA reduction was accompanied by flu-like syndromes, whereas TBW decline was more frequently associated with fatigue and cephalgia. Discussion: BIA offers a sophisticated analysis of body composition including BF, BCM and TBW for HCV patients following antiviral regimens.
PA reduction was associated with increased adverse effects of the antiviral therapy allowing a more dynamic therapy application.
Author: Alisan KahramanJohannes HilsenbeckMonika NygaJudith ErtleAlexander WreeMathias PlauthGuido GerkenAli Canbay
Credits/Source: Virology Journal 2010, 7:191
Published on: 2010-08-16
Source
Lichen Planus and Hepatitis C Virus— Related Chronic Active Hepatitis
Carine Jubert, MD; Jean-Michel Pawlotsky, MD; Florence Pouget, MD; Chantal Andre, PhD; Lionel DeForges; Stéphane Bretagne, MD; Jean-Philippe Mavier, MD, PhD; Jean Duval, MD; Jean Revuz, MD; Daniel Dhumeaux, MD; Martine Bagot, MD, PhD
Arch Dermatol. 1994;130(1):73-76.
Abstract
Background and Design
An increased prevalence of chronic liver disease has been reported in patients with lichen planus (LP). We report six cases of LP associated with chronic active hepatitis and actively replicating hepatitis C virus (HCV).
Results
We studied six patients (three men and three women; mean age, 61 years; age range, 47 to 70 years) with various forms (cutaneous and/or mucosal) of LP and abnormal liver test results. Four patients had severe mucosal lesions. Cutaneous and mucosal lesions had a long-term evolution. Liver disease was discovered 2 to 6 years before LP in three cases and was diagnosed at the same time as LP in the three other cases. Liver biopsy performed in five patients showed chronic active hepatitis without cirrhosis in all five cases. Anti—HCV antibodies were detected in all cases by second-generation enzyme-linked immunosorbent assay and confirmed by second-generation recombinant immunoblot assay. Hepatitis C virus RNA was evidenced by means of polymerase chain reaction in the serum samples from the six patients, proving active viral replication.
Conclusions
Lichen planus may be associated with HCV-related chronic active hepatitis. As interferon treatment may induce viral inactivation in some patients with HCV-related chronic liver disease, a search for HCV infection should be systematically performed in patients with chronic LP.
(Arch Dermatol. 1994;130:73-76)
Author Affiliations
From the Departments of Dermatology (Drs Jubert, Pouget, Revuz, and Bagot), Bacteriology and Virology (Drs Pawlotsky, DeForges, Bretagne, and Duval), Immunology (Dr Andre), and Hepatology (Drs Mavier and Dhumeaux), University of Paris XII, Créteil, France.
Source
Arch Dermatol. 1994;130(1):73-76.
Abstract
Background and Design
An increased prevalence of chronic liver disease has been reported in patients with lichen planus (LP). We report six cases of LP associated with chronic active hepatitis and actively replicating hepatitis C virus (HCV).
Results
We studied six patients (three men and three women; mean age, 61 years; age range, 47 to 70 years) with various forms (cutaneous and/or mucosal) of LP and abnormal liver test results. Four patients had severe mucosal lesions. Cutaneous and mucosal lesions had a long-term evolution. Liver disease was discovered 2 to 6 years before LP in three cases and was diagnosed at the same time as LP in the three other cases. Liver biopsy performed in five patients showed chronic active hepatitis without cirrhosis in all five cases. Anti—HCV antibodies were detected in all cases by second-generation enzyme-linked immunosorbent assay and confirmed by second-generation recombinant immunoblot assay. Hepatitis C virus RNA was evidenced by means of polymerase chain reaction in the serum samples from the six patients, proving active viral replication.
Conclusions
Lichen planus may be associated with HCV-related chronic active hepatitis. As interferon treatment may induce viral inactivation in some patients with HCV-related chronic liver disease, a search for HCV infection should be systematically performed in patients with chronic LP.
(Arch Dermatol. 1994;130:73-76)
Author Affiliations
From the Departments of Dermatology (Drs Jubert, Pouget, Revuz, and Bagot), Bacteriology and Virology (Drs Pawlotsky, DeForges, Bretagne, and Duval), Immunology (Dr Andre), and Hepatology (Drs Mavier and Dhumeaux), University of Paris XII, Créteil, France.
Source
Infection with HIV and HCV enhances the release of fatty acid synthase into circulation: evidence for a novel indicator of viral infection
Fatty acid synthase (FASN) is an enzyme synthesized by the liver and plays an important role in lipogenesis. The present study aimed to investigate whether serum FASN concentration may provide a direct link between HIV and/or HCV viral infections and lipid metabolic disorders commonly observed in HIV/HCV-infected patients.
Methods: We evaluated serum FASN concentration in 191 consecutive HIV-infected patients in the absence or presence of HCV co-infection.
For comparison, 102 uninfected controls were included. Metabolic and inflammatory phenotype was also compared with respect to the presence of HCV co-infection.
Results: Serum FASN concentration was significantly higher in HIV-infected patients than in healthy participants and HCV co-infected patients showed higher levels than those without co-infection.
Levels were also affected by treatment regimen, but marginally influenced by virological variables. Insulin concentration was the sole variable among metabolic parameters that demonstrated a significant correlation with serum FASN concentrations.
Serum alanine aminotransferase (ALT) values correlated significantly with serum FASN concentration and provided the best discrimination with respect to the presence or absence of HCV co-infection. In multivariate analysis, only ALT, monocyte chemoattractant protein-1 (MCP-1) and the presence of antiretroviral treatment regimen significantly contributed to explain serum FASN concentration in HIV/HCV co-infected patients.
Conclusion: Serum FASN concentration is significantly increased in HIV-infected individuals.
The release of FASN into the circulation is further enhanced in patients who are co-infected with HCV. Subsequent studies should explore the usefulness of this indicator to monitor the effect of viral infections on disease progression and survival.
Author: Gerard AragonesCarlos Alonso-VillaverdeCristina Oliveras-FerrarosRaul Beltran-DebonAnna RullFernando Rodriguez-SanabriaJordi CampsAlejandro Vazquez-MartinJavier MenendezJorge Joven
Credits/Source: BMC Gastroenterology 2010, 10:92
Published on: 2010-08-13
Source
Methods: We evaluated serum FASN concentration in 191 consecutive HIV-infected patients in the absence or presence of HCV co-infection.
For comparison, 102 uninfected controls were included. Metabolic and inflammatory phenotype was also compared with respect to the presence of HCV co-infection.
Results: Serum FASN concentration was significantly higher in HIV-infected patients than in healthy participants and HCV co-infected patients showed higher levels than those without co-infection.
Levels were also affected by treatment regimen, but marginally influenced by virological variables. Insulin concentration was the sole variable among metabolic parameters that demonstrated a significant correlation with serum FASN concentrations.
Serum alanine aminotransferase (ALT) values correlated significantly with serum FASN concentration and provided the best discrimination with respect to the presence or absence of HCV co-infection. In multivariate analysis, only ALT, monocyte chemoattractant protein-1 (MCP-1) and the presence of antiretroviral treatment regimen significantly contributed to explain serum FASN concentration in HIV/HCV co-infected patients.
Conclusion: Serum FASN concentration is significantly increased in HIV-infected individuals.
The release of FASN into the circulation is further enhanced in patients who are co-infected with HCV. Subsequent studies should explore the usefulness of this indicator to monitor the effect of viral infections on disease progression and survival.
Author: Gerard AragonesCarlos Alonso-VillaverdeCristina Oliveras-FerrarosRaul Beltran-DebonAnna RullFernando Rodriguez-SanabriaJordi CampsAlejandro Vazquez-MartinJavier MenendezJorge Joven
Credits/Source: BMC Gastroenterology 2010, 10:92
Published on: 2010-08-13
Source
New stem cell discovery a preliminary step for regenerative medicine
Published: 16 August 2010
A discovery by researchers at UQ's Australian Institute for Bioengineering and Nanotechnology (AIBN) will enable better methods to grow stem cells for use in cancer research and regenerative medicine.
The research team led by AIBN's Associate Professor Ernst Wolvetang found that the inclusion of vitamin C in cell culture media was responsible for chemical modification of DNA which has been known to cause chromosome instability and cancer in laboratory stem cell populations.
According to Dr Wolvetang, this discovery is important for stem cell researchers because they rely on genetically stable, non-cancerous stem cells to develop methods to repair damaged or diseased tissues.
“In order to obtain sufficient cells for regenerative medicine applications, human pluripotent stem cells are grown in the laboratory to increase the number of cells,” Dr Wolvetang said.
“Because vitamin C is essential for human health, we were surprised that it had such a detrimental effect on stem cells in culture.
“We found that it causes widespread yet specific loss of DNA-methylation in stem cells, a chemical modification crucial to normal development and cellular differentiation in mammals.
“With this knowledge we can develop better methods to grow stem cells in the laboratory, which will improve our understanding of them and how we might harness their potential in the fight against disease,” he said.
Stem cells are an attractive tool in treating cancer and many other diseases due to their ability to differentiate into any cell type in the human body.
This work was the subject of two publications in the international journal Stem Cells.
AIBN is a multidisciplinary research institute focused on addressing some of the intricate problems in the areas of health, energy and the environment.
Media contact Associate Professor Wolvetang +61 7 3346 3894
Source
A discovery by researchers at UQ's Australian Institute for Bioengineering and Nanotechnology (AIBN) will enable better methods to grow stem cells for use in cancer research and regenerative medicine.
The research team led by AIBN's Associate Professor Ernst Wolvetang found that the inclusion of vitamin C in cell culture media was responsible for chemical modification of DNA which has been known to cause chromosome instability and cancer in laboratory stem cell populations.
According to Dr Wolvetang, this discovery is important for stem cell researchers because they rely on genetically stable, non-cancerous stem cells to develop methods to repair damaged or diseased tissues.
“In order to obtain sufficient cells for regenerative medicine applications, human pluripotent stem cells are grown in the laboratory to increase the number of cells,” Dr Wolvetang said.
“Because vitamin C is essential for human health, we were surprised that it had such a detrimental effect on stem cells in culture.
“We found that it causes widespread yet specific loss of DNA-methylation in stem cells, a chemical modification crucial to normal development and cellular differentiation in mammals.
“With this knowledge we can develop better methods to grow stem cells in the laboratory, which will improve our understanding of them and how we might harness their potential in the fight against disease,” he said.
Stem cells are an attractive tool in treating cancer and many other diseases due to their ability to differentiate into any cell type in the human body.
This work was the subject of two publications in the international journal Stem Cells.
AIBN is a multidisciplinary research institute focused on addressing some of the intricate problems in the areas of health, energy and the environment.
Media contact Associate Professor Wolvetang +61 7 3346 3894
Source
Superior response to pegylated interferon and ribavirin in Asians with chronic hepatitis C
Hepatology International
DOI: 10.1007/s12072-010-9207-1
Venessa Pattullo, E. Jenny Heathcote and David K. H. Wong
Abstract
Purpose
Reported sustained virological response (SVR) rates in Asians with chronic hepatitis C (CHC) exceed those of other ethnic groups, but differences in body weight across races potentially confound this observed superior response. Our aim was to determine whether Asian race independently predicts SVR within a multicultural clinic setting.
Methods
Patients with genotype 1, 2 and 3 CHC prescribed peginterferon and weight-based ribavirin were included in this retrospective study. Logistic regression was performed to identify factors associated with SVR.
Results
Three-hundred ninety-two patients (BMI 26.9 ± 5.0 kg/m2, genotype 1 66%, viral load 5.9 ± 0.66 log10 IU/ml, advanced fibrosis 53%) were included in this study. Caucasians comprised 81%, South Asians 9% and Asians (Non-South) 10%. SVR was achieved by 54% overall, but was highest amongst Asians (Non-South) (79%) compared with South Asians (56%, P = 0.04) and Caucasians (50%, P < 0.001) despite a predominance of genotype 3 infection amongst the South Asians. Asians (Non-South) had the highest SVR rate even amongst those infected with genotype 1 (75%) and those with advanced fibrosis (77%). Independent of viral genotype, Asian (Non-South) race was a strong predictor of SVR (OR 5.10 vs. Caucasians, 95% CI 1.72–17.71, OR 7.84 vs. South Asians, 95% CI 1.62–37.84), as were treatment naïve status (OR 3.85, 95% CI 1.76–8.89), non-diabetic status (OR 3.70, 95% CI 1.30–11.11), non-obesity (OR 2.13, 95% CI 1.06–4.35), peginterferon α2a (2.08 vs. α2b, 95% CI 1.16–3.85), steatosis <10% (OR 2.0, 95% CI 1.05–3.85) and ribavirin exposure (mg/kg/day) (OR 1.13, 95% CI 1.01–1.28).
Conclusion
Asian (Non-South) race is a strong independent predictor of SVR.
Keywords Asian - Sustained virological response - Body mass index - Weight - Obesity - Diabetes - Chronic hepatitis C
Source
DOI: 10.1007/s12072-010-9207-1
Venessa Pattullo, E. Jenny Heathcote and David K. H. Wong
Abstract
Purpose
Reported sustained virological response (SVR) rates in Asians with chronic hepatitis C (CHC) exceed those of other ethnic groups, but differences in body weight across races potentially confound this observed superior response. Our aim was to determine whether Asian race independently predicts SVR within a multicultural clinic setting.
Methods
Patients with genotype 1, 2 and 3 CHC prescribed peginterferon and weight-based ribavirin were included in this retrospective study. Logistic regression was performed to identify factors associated with SVR.
Results
Three-hundred ninety-two patients (BMI 26.9 ± 5.0 kg/m2, genotype 1 66%, viral load 5.9 ± 0.66 log10 IU/ml, advanced fibrosis 53%) were included in this study. Caucasians comprised 81%, South Asians 9% and Asians (Non-South) 10%. SVR was achieved by 54% overall, but was highest amongst Asians (Non-South) (79%) compared with South Asians (56%, P = 0.04) and Caucasians (50%, P < 0.001) despite a predominance of genotype 3 infection amongst the South Asians. Asians (Non-South) had the highest SVR rate even amongst those infected with genotype 1 (75%) and those with advanced fibrosis (77%). Independent of viral genotype, Asian (Non-South) race was a strong predictor of SVR (OR 5.10 vs. Caucasians, 95% CI 1.72–17.71, OR 7.84 vs. South Asians, 95% CI 1.62–37.84), as were treatment naïve status (OR 3.85, 95% CI 1.76–8.89), non-diabetic status (OR 3.70, 95% CI 1.30–11.11), non-obesity (OR 2.13, 95% CI 1.06–4.35), peginterferon α2a (2.08 vs. α2b, 95% CI 1.16–3.85), steatosis <10% (OR 2.0, 95% CI 1.05–3.85) and ribavirin exposure (mg/kg/day) (OR 1.13, 95% CI 1.01–1.28).
Conclusion
Asian (Non-South) race is a strong independent predictor of SVR.
Keywords Asian - Sustained virological response - Body mass index - Weight - Obesity - Diabetes - Chronic hepatitis C
Source
HCV/HIV Patients Who Fail IFN/ribavirin Can Still Use Protease Inhibitors
NEW YORK (Reuters Health) Aug 13 - In patients being simultaneously treated for HIV and hepatitis C virus (HCV), treating the HCV with interferon and ribavirin doesn't change its protease gene diversity nor make it resistant to protease inhibitors (PI), a new study has shown.
In other words, it looks as if "prior HCV treatment with interferon-ribavirin would not markedly impact the potential efficacy of subsequent HCV protease inhibitors treatment in coinfected patients," the researchers report in an August 3rd online article in the Journal of Infectious Diseases.
A majority of the patients in the study had not responded to interferon-ribavirin, but neither did they develop PI resistance mutations in the crucial HCV non structural protein gene 3 (NS3). This gene codes for an HCV protease with an important role in viral replication, the researchers explain.
The rapid multiplication of HCV RNA polymerase results in many circulating variants of the virus called quasispecies, some of which may carry resistant mutations, lead researcher Dr. Aarthi Chary from the Veterans Affairs Palo Alto Health Care System, California and colleagues write.
As a part of a wider prospective analysis of interferon-ribavirin treatment of HCV, the researchers evaluated the variations in HCV NS3 genes in 26 coinfected patients. All were receiving antiretroviral therapy (ART) for HIV, along with weekly or fortnightly subcutaneous interferon and daily oral ribavirin for HCV.
Eleven patients achieved a sustained viral response to interferon/ribavirin.
Baseline diversity in the NS3 gene prior to starting treatment, measured as the median inter nucleotide distance, was significantly greater in the patients who did not respond or who relapsed, the report says.
However, interferon-ribavirin treatment did not induce any new changes in the gene diversity or HCV protease inhibitor resistant mutations.
Although the study size was small, these results substantiate the potential role of HCV-protease inhibitors in difficult-to-treat HCV infections, the researchers write.
"As HCV protease inhibitors are introduced in clinical practice, further understanding of HCV NS3 diversity in this therapeutically challenging coinfected population is needed," Dr. Chary's team concludes.
J Infect Dis. Posted online August 3, 2010. Abstract
Source
In other words, it looks as if "prior HCV treatment with interferon-ribavirin would not markedly impact the potential efficacy of subsequent HCV protease inhibitors treatment in coinfected patients," the researchers report in an August 3rd online article in the Journal of Infectious Diseases.
A majority of the patients in the study had not responded to interferon-ribavirin, but neither did they develop PI resistance mutations in the crucial HCV non structural protein gene 3 (NS3). This gene codes for an HCV protease with an important role in viral replication, the researchers explain.
The rapid multiplication of HCV RNA polymerase results in many circulating variants of the virus called quasispecies, some of which may carry resistant mutations, lead researcher Dr. Aarthi Chary from the Veterans Affairs Palo Alto Health Care System, California and colleagues write.
As a part of a wider prospective analysis of interferon-ribavirin treatment of HCV, the researchers evaluated the variations in HCV NS3 genes in 26 coinfected patients. All were receiving antiretroviral therapy (ART) for HIV, along with weekly or fortnightly subcutaneous interferon and daily oral ribavirin for HCV.
Eleven patients achieved a sustained viral response to interferon/ribavirin.
Baseline diversity in the NS3 gene prior to starting treatment, measured as the median inter nucleotide distance, was significantly greater in the patients who did not respond or who relapsed, the report says.
However, interferon-ribavirin treatment did not induce any new changes in the gene diversity or HCV protease inhibitor resistant mutations.
Although the study size was small, these results substantiate the potential role of HCV-protease inhibitors in difficult-to-treat HCV infections, the researchers write.
"As HCV protease inhibitors are introduced in clinical practice, further understanding of HCV NS3 diversity in this therapeutically challenging coinfected population is needed," Dr. Chary's team concludes.
J Infect Dis. Posted online August 3, 2010. Abstract
Source
Out of Grief Sprouts a Life-Saving Legacy
By JANE E. BRODY
Published: August 16, 2010
You don’t have to be rich, famous or even an adult to leave a memorable legacy that can change lives.
Just ask Stacey Oglesby of Lockwood, Mo., whose 15-year-old daughter, Colbey, died in a car accident in 2001. Colbey had told her mother that when she got her driver’s license, she was going to sign up to be an organ donor. So when hospital personnel asked about organ donation, Ms. Oglesby said, “we had no hesitancy.”
Seven people got Colbey’s organs. Her lungs went to Valerie Vandervort, a 29-year-old Oklahoma woman with cystic fibrosis. In the nine years since, Ms. Vandervort has run three 5K races, hiked a mountain, danced at her sister’s wedding, doted on her nieces and nephews, and won medals in swimming at the 2010 National Kidney Foundation United States Transplant Games.
Ms. Oglesby also befriended the recipient of Colbey’s heart, Judy Kaufman of Chesterfield, Mo., who was near death with congestive heart failure. When they met, Ms. Oglesby took a stethoscope to listen to the beat of her daughter’s heart.
Ms. Oglesby, who speaks often about Colbey’s legacy, said she has inspired others to become potential organ donors. If not for donating her daughter’s organs and connecting to the recipients, she said, “it would have been hard to get through the grief.”
A Widespread Need
At any given time in the United States, more than 100,000 people are waiting for donor organs, more than 10 times as many as become available. Some die waiting; others get sicker and sicker, sometimes too ill to survive when a suitable organ finally becomes available.
In addition to kidneys, heart, lungs, liver, pancreas and intestines, donations can include tissues like corneas, skin, heart valves, bone, veins, cartilage, middle ear, tendons and ligaments that can be stored in tissue banks and used when needed.
Most donations come from people who die suddenly, usually from an accident, a gunshot or a brief illness that resulted in brain death. (A small but growing number of donations follow cardiac death.) Some adults indicate their wish to be donors by signing the back of their driver’s license or a donor card or simply telling their next of kin. For minors, hospital personnel often ask the distraught parents if they would consider donating their child’s organs.
But when 6-year-old Katie Coolican died in 1983 from an undiagnosed heart malformation, it was her mother, Maggie, a nurse, who asked about donating the child’s organs — “to make some sense of it all,” Ms. Coolican, of East Hampton, Conn., said in an interview.
“We were willing to donate anything,” she added, “but at the time all they could use were Katie’s corneas and kidneys.”
Likewise for Julie Schlueter of Winsted, Minn., whose daughter, Missy, 10, died of a cerebral hemorrhage in 1992: donating the girl’s organs meant her loss was not in vain.
Missy’s liver and one kidney went to a man who four years later won a silver medal in the Summer Olympics in Atlanta; he sent the medal to the Schlueters to thank them for enabling him to live. Two toddlers, one from Italy and the other from Colorado, got Missy’s heart valves. And an Iowa woman, then 47, got her other kidney and is still doing well 18 years later.
Rose D’Acquisto of St. Paul said that donating all her husband’s usable organs “has led to things I’d never imagined.”
Her husband, Tony, died in 1996 at age 35 when an undiagnosed brain tumor hemorrhaged and left him in an irreversible coma. Ms. D’Acquisto said the recipient of his liver — an Indiana man near death with a rare liver disease — had now been married more than 30 years and has three grown children.
And the Minnesota farmer who got one of Tony’s kidneys got his life back; he had spent three years traveling three hours a day three times a week for dialysis.
Ms. D’Acquisto, now remarried, says she continues to write and speak about organ donation as love’s greatest gift. Along with Ms. Schlueter, she was among more than 7,000 people who attended the Transplant Games last month in Madison, Wis.
When Katie Coolican died, there was no follow-up care for families who donate the organs of their loved ones. After a few years of struggling with grief, her mother wrote about her experience in The American Journal of Nursing and began speaking about organ donation all over the country.
She went back to school, got a master’s degree and wrote a booklet, “For Those Who Give and Grieve,” that was published by the National Kidney Foundation. (The foundation also publishes a quarterly newsletter with that title, edited by Ms. D’Acquisto.)
“Katie’s had a wonderful legacy that continues to this day,” Ms. Coolican said. In 1992 she founded the National Donor Family Council for the kidney foundation to help grieving families that donate loved ones’ organs and tissues. The two-year follow-up program she created for families has become a model for organ donation programs throughout the country.
(To read more “gift of life” stories about organ donation, see the Web site org/gift/index.html.)
Who Is Eligible to Give?
Do not rule yourself out as a potential donor because you think you may be too ill or too old. Only a few circumstances, like pervasive infection or active cancer, absolutely preclude organ donation, and there is no age limit. People in their 80s and 90s have been successful donors of certain tissues, as have newborns. But for anyone under 18, a parent or guardian must approve the donation.
Even if a person dies after an illness that precludes organ donation, or if too much time elapsed after death for organs to be viable, there is still the opportunity of whole-body donation to a medical college, where the body can be used in research or to help students learn anatomy.
While it is best to register one’s interest in whole-body donation with a medical school in advance of death, after death it is up to the next of kin to make it happen. You no longer own your body after you die. If this is something you would want for yourself, discuss it with your spouse and children, who must agree with your wishes.
Most religions support organ donation as a charitable act, although some may not condone whole-body donation. Check the Web site http://www.organdonor.gov/ and click on “Religious Views on Donation” for guidance.
Source
Published: August 16, 2010
You don’t have to be rich, famous or even an adult to leave a memorable legacy that can change lives.
Just ask Stacey Oglesby of Lockwood, Mo., whose 15-year-old daughter, Colbey, died in a car accident in 2001. Colbey had told her mother that when she got her driver’s license, she was going to sign up to be an organ donor. So when hospital personnel asked about organ donation, Ms. Oglesby said, “we had no hesitancy.”
Seven people got Colbey’s organs. Her lungs went to Valerie Vandervort, a 29-year-old Oklahoma woman with cystic fibrosis. In the nine years since, Ms. Vandervort has run three 5K races, hiked a mountain, danced at her sister’s wedding, doted on her nieces and nephews, and won medals in swimming at the 2010 National Kidney Foundation United States Transplant Games.
Ms. Oglesby also befriended the recipient of Colbey’s heart, Judy Kaufman of Chesterfield, Mo., who was near death with congestive heart failure. When they met, Ms. Oglesby took a stethoscope to listen to the beat of her daughter’s heart.
Ms. Oglesby, who speaks often about Colbey’s legacy, said she has inspired others to become potential organ donors. If not for donating her daughter’s organs and connecting to the recipients, she said, “it would have been hard to get through the grief.”
A Widespread Need
At any given time in the United States, more than 100,000 people are waiting for donor organs, more than 10 times as many as become available. Some die waiting; others get sicker and sicker, sometimes too ill to survive when a suitable organ finally becomes available.
In addition to kidneys, heart, lungs, liver, pancreas and intestines, donations can include tissues like corneas, skin, heart valves, bone, veins, cartilage, middle ear, tendons and ligaments that can be stored in tissue banks and used when needed.
Most donations come from people who die suddenly, usually from an accident, a gunshot or a brief illness that resulted in brain death. (A small but growing number of donations follow cardiac death.) Some adults indicate their wish to be donors by signing the back of their driver’s license or a donor card or simply telling their next of kin. For minors, hospital personnel often ask the distraught parents if they would consider donating their child’s organs.
But when 6-year-old Katie Coolican died in 1983 from an undiagnosed heart malformation, it was her mother, Maggie, a nurse, who asked about donating the child’s organs — “to make some sense of it all,” Ms. Coolican, of East Hampton, Conn., said in an interview.
“We were willing to donate anything,” she added, “but at the time all they could use were Katie’s corneas and kidneys.”
Likewise for Julie Schlueter of Winsted, Minn., whose daughter, Missy, 10, died of a cerebral hemorrhage in 1992: donating the girl’s organs meant her loss was not in vain.
Missy’s liver and one kidney went to a man who four years later won a silver medal in the Summer Olympics in Atlanta; he sent the medal to the Schlueters to thank them for enabling him to live. Two toddlers, one from Italy and the other from Colorado, got Missy’s heart valves. And an Iowa woman, then 47, got her other kidney and is still doing well 18 years later.
Rose D’Acquisto of St. Paul said that donating all her husband’s usable organs “has led to things I’d never imagined.”
Her husband, Tony, died in 1996 at age 35 when an undiagnosed brain tumor hemorrhaged and left him in an irreversible coma. Ms. D’Acquisto said the recipient of his liver — an Indiana man near death with a rare liver disease — had now been married more than 30 years and has three grown children.
And the Minnesota farmer who got one of Tony’s kidneys got his life back; he had spent three years traveling three hours a day three times a week for dialysis.
Ms. D’Acquisto, now remarried, says she continues to write and speak about organ donation as love’s greatest gift. Along with Ms. Schlueter, she was among more than 7,000 people who attended the Transplant Games last month in Madison, Wis.
When Katie Coolican died, there was no follow-up care for families who donate the organs of their loved ones. After a few years of struggling with grief, her mother wrote about her experience in The American Journal of Nursing and began speaking about organ donation all over the country.
She went back to school, got a master’s degree and wrote a booklet, “For Those Who Give and Grieve,” that was published by the National Kidney Foundation. (The foundation also publishes a quarterly newsletter with that title, edited by Ms. D’Acquisto.)
“Katie’s had a wonderful legacy that continues to this day,” Ms. Coolican said. In 1992 she founded the National Donor Family Council for the kidney foundation to help grieving families that donate loved ones’ organs and tissues. The two-year follow-up program she created for families has become a model for organ donation programs throughout the country.
(To read more “gift of life” stories about organ donation, see the Web site org/gift/index.html.)
Who Is Eligible to Give?
Do not rule yourself out as a potential donor because you think you may be too ill or too old. Only a few circumstances, like pervasive infection or active cancer, absolutely preclude organ donation, and there is no age limit. People in their 80s and 90s have been successful donors of certain tissues, as have newborns. But for anyone under 18, a parent or guardian must approve the donation.
Even if a person dies after an illness that precludes organ donation, or if too much time elapsed after death for organs to be viable, there is still the opportunity of whole-body donation to a medical college, where the body can be used in research or to help students learn anatomy.
While it is best to register one’s interest in whole-body donation with a medical school in advance of death, after death it is up to the next of kin to make it happen. You no longer own your body after you die. If this is something you would want for yourself, discuss it with your spouse and children, who must agree with your wishes.
Most religions support organ donation as a charitable act, although some may not condone whole-body donation. Check the Web site http://www.organdonor.gov/ and click on “Religious Views on Donation” for guidance.
Source
August 16, 2010
Fittest hepatitis C viruses infect transplanted livers
Public release date: 16-Aug-2010
Contact: Rita Sullivan
news@rockefeller.edu
212-327-8603
Rockefeller University Press
Not all viruses are created equal. In liver transplant patients with chronic hepatitis C virus (HCV) infection, only viruses that can dodge the immune response invade the new liver, according to a study published on August 16 in The Journal of Experimental Medicine (http://www.jem.org/).
Chronic HCV infection is the leading indication for liver transplantation in the US. But installing a new liver does not cure disease; in fact, HCV infects the transplanted liver in nearly all patients. However, only a subset of the viruses present prior to transplantation show up in the new organ, according to a study lead by Francoise Stoll-Keller and Thomas Baumert at the University of Strasbourg in France. Compared to many of their pre-transplant brethren, the viruses that invaded the new organ infected liver cells more readily and were impervious to the antibodies that normally block infection.
In most patients, the post-transplant viruses had mutations in one region of the surface protein the virus uses to infect cells. Blocking this region may thus provide a new way to prevent reinfection after liver transplant.
###
About The Journal of Experimental Medicine
The Journal of Experimental Medicine (JEM) is published by The Rockefeller University Press. All editorial decisions on manuscripts submitted are made by active scientists in conjunction with our in-house scientific editors. JEM content is posted to PubMed Central, where it is available to the public for free six months after publication. Authors retain copyright of their published works and third parties may reuse the content for non-commercial purposes under a creative commons license. For more information, please visit http://www.jem.org/.
Fafi-Kremer, S., et al. 2010. J. Exp. Med. doi:10.1084/jem.20090766.
Source
Contact: Rita Sullivan
news@rockefeller.edu
212-327-8603
Rockefeller University Press
Not all viruses are created equal. In liver transplant patients with chronic hepatitis C virus (HCV) infection, only viruses that can dodge the immune response invade the new liver, according to a study published on August 16 in The Journal of Experimental Medicine (http://www.jem.org/).
Chronic HCV infection is the leading indication for liver transplantation in the US. But installing a new liver does not cure disease; in fact, HCV infects the transplanted liver in nearly all patients. However, only a subset of the viruses present prior to transplantation show up in the new organ, according to a study lead by Francoise Stoll-Keller and Thomas Baumert at the University of Strasbourg in France. Compared to many of their pre-transplant brethren, the viruses that invaded the new organ infected liver cells more readily and were impervious to the antibodies that normally block infection.
In most patients, the post-transplant viruses had mutations in one region of the surface protein the virus uses to infect cells. Blocking this region may thus provide a new way to prevent reinfection after liver transplant.
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About The Journal of Experimental Medicine
The Journal of Experimental Medicine (JEM) is published by The Rockefeller University Press. All editorial decisions on manuscripts submitted are made by active scientists in conjunction with our in-house scientific editors. JEM content is posted to PubMed Central, where it is available to the public for free six months after publication. Authors retain copyright of their published works and third parties may reuse the content for non-commercial purposes under a creative commons license. For more information, please visit http://www.jem.org/.
Fafi-Kremer, S., et al. 2010. J. Exp. Med. doi:10.1084/jem.20090766.
Source
Donor Risk Index does not impact outcomes on a small scale
August 16, 2010
The Donor Risk Index, which assesses donor characteristics impacting liver transplantation outcomes, does not bear the same impact on outcomes on a small scale as is suggested from large-scale, national data.
Rather, hepatitis C was shown to continue to be the major contributor to poor graft survival in transplant patients, according to a Henry Ford Hospital.
The goals of the study were to confirm the effect of the Donor Risk Index on liver transplant recipients and to evaluate further donor and recipient characteristics on transplant outcomes.
"We found the risks to be small for individual characteristics influencing outcomes except for hepatitis C," says Marwan Abouljoud, M.D., director of Henry Ford Hospital's Transplant Institute and lead author of the study.
"Looking at data from large studies is like looking under a microscope and when the information from many of these national studies is translated to day-to-day practice, the information often doesn't prove to be practical, especially when you consider patients are dying on transplant waiting lists."
Study results were presented today at the International Congress of The Transplantation Society in Vancouver.
The study looked at the DRI scores for 100 liver transplants between January and December 2008, analyzing recipients and their corresponding donors. Donor and recipient demographics, model for end-stage liver disease (MELD) scores, laboratory data, operative factors and pathologists were reviewed.
The presence of hepatitis in recipients post-transplant was found to have the biggest impact on mortality and graft failure. Death rate was 22 percent, of which 41 percent died due to recurrent hepatitis. The graft failure rate was 20 percent with hepatitis the cause in 44 percent of the cases.
The only Donor Risk Index subcategory that was associated with graft loss in the study was high donor age, says Dr. Abouljoud, who suggests that further study is needed to favorably impact graft survival within the context of the Donor Risk Index.
"Our findings suggest that the focus should be on the combined factors that effect organ quality and function, not one individual characteristic," says Dr. Abouljoud.
Currently, almost 16,000 people in the United States are waiting for liver transplants, according to the Health Resources and Services Administration. About 5,300 liver transplantations were performed in the United States in 2002.
Provided by Henry Ford Health System
Source
The Donor Risk Index, which assesses donor characteristics impacting liver transplantation outcomes, does not bear the same impact on outcomes on a small scale as is suggested from large-scale, national data.
Rather, hepatitis C was shown to continue to be the major contributor to poor graft survival in transplant patients, according to a Henry Ford Hospital.
The goals of the study were to confirm the effect of the Donor Risk Index on liver transplant recipients and to evaluate further donor and recipient characteristics on transplant outcomes.
"We found the risks to be small for individual characteristics influencing outcomes except for hepatitis C," says Marwan Abouljoud, M.D., director of Henry Ford Hospital's Transplant Institute and lead author of the study.
"Looking at data from large studies is like looking under a microscope and when the information from many of these national studies is translated to day-to-day practice, the information often doesn't prove to be practical, especially when you consider patients are dying on transplant waiting lists."
Study results were presented today at the International Congress of The Transplantation Society in Vancouver.
The study looked at the DRI scores for 100 liver transplants between January and December 2008, analyzing recipients and their corresponding donors. Donor and recipient demographics, model for end-stage liver disease (MELD) scores, laboratory data, operative factors and pathologists were reviewed.
The presence of hepatitis in recipients post-transplant was found to have the biggest impact on mortality and graft failure. Death rate was 22 percent, of which 41 percent died due to recurrent hepatitis. The graft failure rate was 20 percent with hepatitis the cause in 44 percent of the cases.
The only Donor Risk Index subcategory that was associated with graft loss in the study was high donor age, says Dr. Abouljoud, who suggests that further study is needed to favorably impact graft survival within the context of the Donor Risk Index.
"Our findings suggest that the focus should be on the combined factors that effect organ quality and function, not one individual characteristic," says Dr. Abouljoud.
Currently, almost 16,000 people in the United States are waiting for liver transplants, according to the Health Resources and Services Administration. About 5,300 liver transplantations were performed in the United States in 2002.
Provided by Henry Ford Health System
Source
Tobacco and other factors have a negative impact on quality of life in hepatitis C patients
D. Yamini, B. Basseri, G. M. Chee, A. Arakelyan, P. Enayati, T. T. Tran, F. Poordad
Journal of Viral Hepatitis
Article first published online: 15 AUG 2010
DOI: 10.1111/j.1365-2893.2010.01361.x
© 2010 Blackwell Publishing Ltd
Author Information
Hepatology Section, Division of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
*Correspondence: Fred Poordad, MD, Chief, Hepatology and Liver Transplantation, Cedars-Sinai Medical Center, 8635 W. 3rd Street #1060-W, Los Angeles, CA 90048, USA. E-mail: Fred.Poordad@cshs.org
Keywords:depression;difficulty sleeping;fatigue;hepatitis C virus;quality of life;sexual dysfunction;smoking
Summary. Hepatitis C virus (HCV) is known to adversely affect general, social, emotional and mental health domains. This study was designed to identify variables that may be associated with these measurable outcomes. We conducted a cross-sectional retrospective review of demographic and clinical data from 800 patients with HCV evaluated between January 1998 and November 2007. Data were collected using a standardized questionnaire filled out by the patients at the first encounter. Variables evaluated included fibrosis stages (i.e. FS0/1/2 vs FS3/4), demographics, comorbid health conditions, tobacco and alcohol use, high-risk social behaviours and laboratory data. Variables assessed were depression, fatigue, problems sleeping and loss of interest in sex. Statistical analysis was performed using univariate and multivariate logistic regression. Depression (29.3%) in our HCV study population was associated with female gender, tobacco use, hyperlipidemia, history of heavy alcohol use and intravenous drug use. Fatigue (44.6%) was associated with end-stage renal disease, past and current tobacco use and current alcohol use. Difficulty sleeping (13.8%) was associated with past and current tobacco use, current alcohol use and diabetes. Loss of interest in sex (7.7%) was associated with current tobacco use, multiple risk factors for HCV and age at time of evaluation. Fibrosis stage (FS) also had a significant positive association with alcohol use (OR 2.61; P = 0.003) and tobacco use (OR 2.00; P = 0.002). Smoking and alcohol use have a significant negative impact on the presence of depression, fatigue, difficulty sleeping and loss of interest in sex in HCV patients. Practitioners should be aware of these associations, particularly tobacco use, which significantly and negatively impacted every variable evaluated.
Source
Journal of Viral Hepatitis
Article first published online: 15 AUG 2010
DOI: 10.1111/j.1365-2893.2010.01361.x
© 2010 Blackwell Publishing Ltd
Author Information
Hepatology Section, Division of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
*Correspondence: Fred Poordad, MD, Chief, Hepatology and Liver Transplantation, Cedars-Sinai Medical Center, 8635 W. 3rd Street #1060-W, Los Angeles, CA 90048, USA. E-mail: Fred.Poordad@cshs.org
Keywords:depression;difficulty sleeping;fatigue;hepatitis C virus;quality of life;sexual dysfunction;smoking
Summary. Hepatitis C virus (HCV) is known to adversely affect general, social, emotional and mental health domains. This study was designed to identify variables that may be associated with these measurable outcomes. We conducted a cross-sectional retrospective review of demographic and clinical data from 800 patients with HCV evaluated between January 1998 and November 2007. Data were collected using a standardized questionnaire filled out by the patients at the first encounter. Variables evaluated included fibrosis stages (i.e. FS0/1/2 vs FS3/4), demographics, comorbid health conditions, tobacco and alcohol use, high-risk social behaviours and laboratory data. Variables assessed were depression, fatigue, problems sleeping and loss of interest in sex. Statistical analysis was performed using univariate and multivariate logistic regression. Depression (29.3%) in our HCV study population was associated with female gender, tobacco use, hyperlipidemia, history of heavy alcohol use and intravenous drug use. Fatigue (44.6%) was associated with end-stage renal disease, past and current tobacco use and current alcohol use. Difficulty sleeping (13.8%) was associated with past and current tobacco use, current alcohol use and diabetes. Loss of interest in sex (7.7%) was associated with current tobacco use, multiple risk factors for HCV and age at time of evaluation. Fibrosis stage (FS) also had a significant positive association with alcohol use (OR 2.61; P = 0.003) and tobacco use (OR 2.00; P = 0.002). Smoking and alcohol use have a significant negative impact on the presence of depression, fatigue, difficulty sleeping and loss of interest in sex in HCV patients. Practitioners should be aware of these associations, particularly tobacco use, which significantly and negatively impacted every variable evaluated.
Source
Ohio man plans fundraiser for local Vietnam veteran
SUBMITTED PHOTO
Hart poses while stationed in the Vietnam War.
By Jill Whalen (Staff Writer)
Published: August 16, 2010
Rick Hart never met Frank Tate. And he probably never will, either.
The two live almost 540 miles from each other. Hart is in Monroe, Ohio; Tate lives in Drums.
Yet Hart, who served as a U.S. Marine during the Vietnam War just as Tate did, decided to hold a fundraiser to help Tate battle the liver disease that is claiming his life.
"I've been helping veterans for a long time," Hart said. But Tate's story really hit a nerve.
Hart learned of Tate's failing health from a Times-Shamrock newspapers article several days ago. Tate, 59, and a few of his doctors believe his cirrhosis is directly linked to his exposure to Agent Orange in Vietnam. The Department of Veterans Affairs, however, does not recognize the toxic chemical as a cause for cirrhosis. And doctors won't attempt a liver transplant, saying the procedure would be too risky since Tate's health is failing.
"I always think that like Frank, that could be me with the Agent Orange. When we were in Vietnam, they told us very little. The less we were told, I guess they thought the better. As a matter of fact, you didn't know what was going on," Hart said.
Like Tate, Hart saw maps of where Agent Orange was used to defoliate forests in Vietnam to expose the enemy.
"I had it dumped on me, too. That could be me. We might have eaten the same dirt," Hart said. "Who would do anything to help me if I was in Frank's situation? Probably nobody. I'm looking at holding this fundraiser as an opportunity to help somebody. It's like they say, what comes around goes around."
Hart sent an e-mail to Tate, and Tate contacted him. When Hart told him his intentions to hold a fundraiser, Tate gave his blessing.
"All he is saying is, 'thank you, thank you, thank you,'" Hart said.
Hart will hold the fundraiser Saturday at his rural home. It will run from noon to midnight, and feature food, drinks and lots of games to play.
Tate's wife, Carol, said she is happy someone is willing to help.
"(Hart) said he's getting things rolling," she said.
Hart printed flyers, and has distributed more than 150 of them so far. He plans to canvass his town, and drop an invitation off at every home displaying a U.S. flag. He also will post notices at a nearby veterans' museum and walk around his neighborhood to personally invite people to his basement club.
The fundraiser will be held in Hart's basement, an area he outfitted with a bar, two jukeboxes, pinball machines and other fun stuff a few years ago after he realized he was one of the older patrons of a sports bar near his home.
"I started my own NCO club," he laughed.
While the "club" started as a fun place for Hart to hang out, it is now opened frequently to raise funds for men and women in uniform. With the proceeds, Hart and his wife, Linda Lou, who was a Navy nurse in the Vietnam War, send special packages to those serving overseas. They've sent coffee, food, snacks, hand-held radios, DVD players, T-shirts from a Hooters restaurant - and anything else the soldiers request.
"It's all about boosting morale," Hart said.
They also open their home regularly to traveling members of the military on active duty. There's a guest room set aside for the soldiers, and the game room is open to them and any other service personnel visiting the area.
"For a few of them, it was the last fun time they had before they went to Iraq because some of them are no longer here," Hart said. A photo of an Army staff sergeant who visited the Harts hangs on one of the walls, paying tribute to the man who died from injuries suffered when his vehicle hit a roadside bomb. Photographs of other visitors also line the walls, as do military-themed items, movie posters, album covers and mannequins.
"I'll do whatever I can to help the veterans. I can't help everybody, but I can help one person," Hart said.
jwhalen@standardspeaker.com, 570-455-3636
Source
Also See: Vietnam veteran running out of options
Liver transplants must be started in Kuwait
Updated on: 16/08/2010
Miami University team to train local doctors
Dr Hussein Hayati is a liver, pancreas and organ transplantation specialist. Along with his team of surgeons and hospital officials, he is working on starting liver transplantation in Kuwait; a process he says is much needed in the country.
Fortunately, he and his team are on the verge of finalizing an agreement with an American team from the university of Miami and a liver transplant unit has been established at the Amiri Hospital currently catering to cancer surgeries and surgical diseases related to the liver, pancreas and the biliary system. These surgeries have also only begun to be performed in Kuwait.
“Kuwait is in need of liver transplantation and we have the facilities to establish this system and if we work hard on deceased donation, we can do 15 to 20 if not more liver transplantation a year. This may reduce the number of people going outside and reduce the costs. A liver transplantation can cost a person a minimum of one million dollars abroad. Liver transplantation will be free of charge here; the expenses will be for the investigations only,” said Dr Hayati.
He added that liver transplantation, procedures are necessary as currently doctors are loosing patients who could have been saved, especially young patients who are nationals and non-nationals.
Q: What does liver transplantation consist of?
A: Liver transplantation is like any other organ transplantation,transferring an organ or organ tissue from a donor to a recipient. It is done in two ways, either you take the liver from a deceased person or brain-dead person or you take it from a living donor who could be a relative or someone with matching criteria.
The diseased liver of the recipient could also be replaced by a piece of liver from the donor. We connect this piece of liver to the recipient and with time the liver grows into almost the size of the liver that he or she needs.
Q: What is the criteria for being a recipient or a donor?
A: Liver transplant is done on those who have liver cirrhosis or liver failure. Liver cirrhosis is the end result for any chronic disease that affects the liver. The most common liver diseases are viruses; we have Hepatitis C and Hepatitis B. They cause chronic illnesses and inflammation which will result is cirrhosis, which means the liver tissue will be replaced by fibrous tissue that is inactive.
There are other causes of chronic liver illness such as alcohol consumption, which is the second common cause for liver failure in the world. Then we have hereditary causes and congenital causes. Either you have enzymatic deficiencies or metabolism problems which these days affect children. However, the most common causes are Hepatitis and alcohol.
Q: What are the most commonly used techniques for liver transplantation?
A: Liver transplantation is done surgically, either transplanting a complete liver or a piece of liver. The techniques for both surgeries are the common. However, if you take the liver from a liver donor it is more time consuming and needs a lot of work because you will end up with two rooms, one for the donor and one for the recipient.
The donor will be under anesthesia and a team will work on him or her to take a piece of liver. Sometimes you need a small piece and sometimes you need a bigger piece. The bigger piece is taken from the right lobe of the liver in adults. In pediatrics, we can take segments. The liver has eight segments and these segments are divided into two lobes anatomically.
That’s why I mentioned piece of liver, cause it could be for a child, they take a segment or two segments of the liver. But if it is an adult, they take either the left or right side, but usually the right side.
The techniques of surgery are slightly different when a piece of liver from a live donor is taken because surgeons will be dealing with smaller liver tissue as well as smaller vessels and ducts that need to be connected. It is more time consuming, if liver is taken from a live donor.
Q: How successful is the live donor liver transplant surgery? How long does it take the recipient and the donor to recover?
A: Usually fit donors with no medical problems are chosen for the surgery, so that you don’t end up with problems during the anesthesia or after the surgery. Their hospital sty is usually five to seven days and then they are discharged. After that it takes three months for the liver to reform and grow to normal size, plus or minus ten percent, and it will appear that no surgery was ever performed.
The situation for the recipient is different and he will take more time to recover because the recipient has taken in a foreign organ to his system or body. He will end up taking medication to reduce his immunity, called immuno-suppressive medication. He will be taking four kinds of medication and then he will be discharged with three kinds which are, with time, withdrawn slowly. If the transplant is from a live donor, the liver will also grow to about normal size.
If a whole liver is transplanted, the recovery time and medications will be the same but the surgery itself is less complicated. The surgeon will be dealing with large structures, bigger vessels and ducts that drain the biliary system, so it is easier to connect the organ to the body.
The life expectancy of a liver transplant recipient depends on the cause of the liver cirrhosis or liver failure. It is divided into viral and non-viral. Viral diseases are Hepatitis B and Hepatitis C. Non-viral causes are alcohol, hereditary problems, congenital problems or enzymatic deficiencies, which is a congenital problem.
Recipients with non-viral liver failure have the best outcome than recipients with viral problems. That is because viruses can come back again when immunity is low and cause damage to the transplanted liver. That is why with the non-viral, we are talking about 95 percent, one year survival and we call it graft survival. It can reach to almost 80 percent, five year survival and ten years you can go to 70 percent.
Recipients with viral disease also divided into two categories; the ones with Hepatitis B and the ones with Hepatitis C. Hepatitis C is the worst because we do not have the proper anti-viral to counteract the effects of the virus.
After the first year of the transplant, there is a 60 percent chance the virus will reoccur. But the amount of damage varies, for some people within three months the liver is completely damaged and they need a re-transplantation. Some people can last for three, four or five years even without any problem.
On the contrary, we have certain antibodies and anti-viral for Hepatitis B. That is why the outcome for Hepatitis B is much better than Hepatitis C. The recurrence of Hepatitis B after transplantation in the transplanted liver is 11 percent. There used to be an 80 percent chance of recurrence, but due to the discover of the anti-viral and antibodies that are included in the treatment regiment, it lowered the chance of recurrence.
Q: Has liver transplantation ever been done in Kuwait?
A: Liver transplantation has not been done yet in Kuwait. We are on the verge of finalizing an agreement with an American team at the University of Miami. We already approached the team and they have visited Kuwait, but we are just waiting for the final agreement.
The team evaluated the facilities in Kuwait and has pointed out that we should start a liver transplant and liver surgery unit at the Amiri Hospital because, according to their evaluation, the Amiri Hospital has the best facilities such as a new ICU and new operating room to avoid infections in these kinds of cases.
Also, we have Al-Thunayan Gestural and Intestinal Center nearby so if we need intervention by endoscopies it is available.
It has been agreed upon by the heads of departments to locate that unite there and the services have already been opened up, but right now we are only doing specialized cancer surgery and operating on surgical diseases related to the liver, pancreas and the biliary system.
These surgeries have only begun to be performed in Kuwait. We have started doing them around a year ago but now we have a specialized place and a team and we are training the ICU and nursing staff to get used to these kinds of cases. We are getting transfers so far from three or four hospitals, excluding Mubarak Hospital.
We are performing one surgery a week because it is not a very common problem but the problem is still there and we are still new and people are still getting used to us. For example, we don’t get transfers for private hospitals, so we need to build a good reputation.
We have the support of the Ministry of Health because we have ministerial decree to establish the unit and to establish the referral system from other hospitals to this unit. So all these specialty surgeries related to the liver, pancreas and the biliary system are done in our unit.
Q: When do you expect liver transplantation to begin in Kuwait?
A: It depends when we get the agreement. There are certain financial issues not finalized yet, but hopefully by the end of this year or early next year.
Q: How necessary is liver transplantation in Kuwait?
A: It is very necessary and we need it. We are loosing patients and especially young patients who are nationals and non-nationals. The non-nationals have Hepatitis C more frequently and the nationals get Hepatitis B often and there are some cases of cirrhosis of an unknown origin, but it is non-viral and non-alcoholic, it can happen like that because there is an entity called idiopathic, we don’t know the cause. There is a small percentage of alcohol related cases as well.
Kuwait is in need of liver transplantation and we have the facilities to establish this system and if we work hard on deceased donation, we can do 15 to 20 if not more transplantation a year. This may reduce the number of people going outside and this may also reduce the cost. A liver transplantation can cost a person a minimum of one million dollars abroad. Liver transplantation will be free of charge here; the expenses will be for the investigations only.
If the services are provided here, it will reduce the costs and it will be much more effective because we are losing young patients. Recently, only in the l last month, we lost an 18-year-old girl to chemical hepatitis. She took more herbal medication and she developed liver failure. She was put into intensive care and we rushed to send her abroad but we didn’t have enough time. She passed away before we were able to send her abroad.
If we had the liver transplant service here, we could have managed to rescue her. There were also similar cases like this one, we have another 28-year-old lady last year, a mother with three children, who took a medication for TB and had a bad reaction that ended with liver failure. We couldn’t save her live.
So the service has to be established and the MoH is working hard on that. They realized that we needed this. They have the expertise in all different specialties but it is just a matter or organization, plus they wanted an outside experienced team to come here so they will gain the trust of the people.
To be honest, there is a lack of trust in the medical services in Kuwait because of awareness problems and political issues. That is why the Minister of Health Dr Hilal Al-Sayer, made an excellent move by bringing in teams for the chest hospital, the cancer center and the transplant center because these are the three main areas we have not built upon in Kuwait. He provided the teams here so that there will be no excuse for going abroad.
Q: Do you have compiled donor list for liver transplantation?
A: We don’t have a donor list; we should have a recipient list according to blood group because evaluating a person consumes a lot of time and money. We cannot do that unless we reach an agreement and have a starting date. If this process takes longer, I have to evaluate the patient again because his status will change with time.
So if we reach an agreement and decide on a starting date, then we can arrange a list of people who are fit for transplants two months prior by contacting all the centers in Kuwait that deal with liver cirrhosis.
We already have 5,000 people with donation cards and their names are registered in Kuwait Society of Organ Transplantation but we are still working on the deceased donation list.
Any program in the world starts with deceased donation, because it is less complicated than living donation. You have to establish a good deceased donation program before you start a living donor program in case the living donors develop problems themselves or living donor transplantation surgeries go wrong.
Dr Mostafa Al-Mousawi is the head of the organ procurement department which started working toward this program in June and is developing a good system. Now we get a good number of reports from the ICUs, it is just that we need to convince the families to donate.
For example, someone who has had an accident and he is comatose in the ICU. We cannot take consent from him; we have to take consent from his family who may even not be in the country.
So the system is being established, it has been there for a long time and is the best system in the Gulf, but we had some drawbacks due to problems with the transplant coordinators. That is why we are sort of re-evaluating the system and the MOH promised to give us more facilities and to establish more teams.
The American team for liver transplantation will include not only surgeons, but physicians, anesthetists, radiologists and coordinators as well who will train out local coordinators. We will have an agreement to send our Kuwaiti coordinators to Miami to be trained and the non-Kuwaitis will be trained here by the Miami team.
So we will have coordinators with different nationalities to communicate with the families from all over the world, such as Egypt, Syria, India and Bangladesh.
Q: Have there been any unique surgeries done so far for the first time in the Gulf?
A: All what we are doing now is new in the Arabian Gulf and we did one case which was not done before in the ME, but these are not done frequently. We do surgeries for cancer of the liver, pancreas, gal bladder and biliary system or tumor and benign conditions that need surgery.
So far we did eight big surgeries since we started in June. We get referrals from different hospitals and some don’t need surgical intervention for the time being.
The case that we did that was unique is called ‘Synchronous Resection’ where we performed two surgeries at the same time on one patient. This patient had cancer of the colon that has spread to the liver. These surgeries are not frequently done because you need special situations and a dedicated and educated patient that can be aware of the risks.
You also need a two-team approach, a team that can handle the colon cancer and a team which can handle the liver, which was our team. When we evaluated the patient, who is 43 years old, we discovered that she had colon cancer and at the same time she had a big metastatic spread of the tumour to the liver. We decided to do the surgery and the patient had a smooth recovery and she was discharged home by day eight.
It is not the surgeries that matter it is the services that you have around. We had excellent ICU care at the Amiri Hospital, the team was superb. The nursing staff in the operating room was excellent as well. You cannot work alone; you need other services to support you and the patient. I hope in the future we get more referrals from different hospitals.
By: Nihal Sharaf
Source
Miami University team to train local doctors
Dr Hussein Hayati is a liver, pancreas and organ transplantation specialist. Along with his team of surgeons and hospital officials, he is working on starting liver transplantation in Kuwait; a process he says is much needed in the country.
Fortunately, he and his team are on the verge of finalizing an agreement with an American team from the university of Miami and a liver transplant unit has been established at the Amiri Hospital currently catering to cancer surgeries and surgical diseases related to the liver, pancreas and the biliary system. These surgeries have also only begun to be performed in Kuwait.
“Kuwait is in need of liver transplantation and we have the facilities to establish this system and if we work hard on deceased donation, we can do 15 to 20 if not more liver transplantation a year. This may reduce the number of people going outside and reduce the costs. A liver transplantation can cost a person a minimum of one million dollars abroad. Liver transplantation will be free of charge here; the expenses will be for the investigations only,” said Dr Hayati.
He added that liver transplantation, procedures are necessary as currently doctors are loosing patients who could have been saved, especially young patients who are nationals and non-nationals.
Q: What does liver transplantation consist of?
A: Liver transplantation is like any other organ transplantation,transferring an organ or organ tissue from a donor to a recipient. It is done in two ways, either you take the liver from a deceased person or brain-dead person or you take it from a living donor who could be a relative or someone with matching criteria.
The diseased liver of the recipient could also be replaced by a piece of liver from the donor. We connect this piece of liver to the recipient and with time the liver grows into almost the size of the liver that he or she needs.
Q: What is the criteria for being a recipient or a donor?
A: Liver transplant is done on those who have liver cirrhosis or liver failure. Liver cirrhosis is the end result for any chronic disease that affects the liver. The most common liver diseases are viruses; we have Hepatitis C and Hepatitis B. They cause chronic illnesses and inflammation which will result is cirrhosis, which means the liver tissue will be replaced by fibrous tissue that is inactive.
There are other causes of chronic liver illness such as alcohol consumption, which is the second common cause for liver failure in the world. Then we have hereditary causes and congenital causes. Either you have enzymatic deficiencies or metabolism problems which these days affect children. However, the most common causes are Hepatitis and alcohol.
Q: What are the most commonly used techniques for liver transplantation?
A: Liver transplantation is done surgically, either transplanting a complete liver or a piece of liver. The techniques for both surgeries are the common. However, if you take the liver from a liver donor it is more time consuming and needs a lot of work because you will end up with two rooms, one for the donor and one for the recipient.
The donor will be under anesthesia and a team will work on him or her to take a piece of liver. Sometimes you need a small piece and sometimes you need a bigger piece. The bigger piece is taken from the right lobe of the liver in adults. In pediatrics, we can take segments. The liver has eight segments and these segments are divided into two lobes anatomically.
That’s why I mentioned piece of liver, cause it could be for a child, they take a segment or two segments of the liver. But if it is an adult, they take either the left or right side, but usually the right side.
The techniques of surgery are slightly different when a piece of liver from a live donor is taken because surgeons will be dealing with smaller liver tissue as well as smaller vessels and ducts that need to be connected. It is more time consuming, if liver is taken from a live donor.
Q: How successful is the live donor liver transplant surgery? How long does it take the recipient and the donor to recover?
A: Usually fit donors with no medical problems are chosen for the surgery, so that you don’t end up with problems during the anesthesia or after the surgery. Their hospital sty is usually five to seven days and then they are discharged. After that it takes three months for the liver to reform and grow to normal size, plus or minus ten percent, and it will appear that no surgery was ever performed.
The situation for the recipient is different and he will take more time to recover because the recipient has taken in a foreign organ to his system or body. He will end up taking medication to reduce his immunity, called immuno-suppressive medication. He will be taking four kinds of medication and then he will be discharged with three kinds which are, with time, withdrawn slowly. If the transplant is from a live donor, the liver will also grow to about normal size.
If a whole liver is transplanted, the recovery time and medications will be the same but the surgery itself is less complicated. The surgeon will be dealing with large structures, bigger vessels and ducts that drain the biliary system, so it is easier to connect the organ to the body.
The life expectancy of a liver transplant recipient depends on the cause of the liver cirrhosis or liver failure. It is divided into viral and non-viral. Viral diseases are Hepatitis B and Hepatitis C. Non-viral causes are alcohol, hereditary problems, congenital problems or enzymatic deficiencies, which is a congenital problem.
Recipients with non-viral liver failure have the best outcome than recipients with viral problems. That is because viruses can come back again when immunity is low and cause damage to the transplanted liver. That is why with the non-viral, we are talking about 95 percent, one year survival and we call it graft survival. It can reach to almost 80 percent, five year survival and ten years you can go to 70 percent.
Recipients with viral disease also divided into two categories; the ones with Hepatitis B and the ones with Hepatitis C. Hepatitis C is the worst because we do not have the proper anti-viral to counteract the effects of the virus.
After the first year of the transplant, there is a 60 percent chance the virus will reoccur. But the amount of damage varies, for some people within three months the liver is completely damaged and they need a re-transplantation. Some people can last for three, four or five years even without any problem.
On the contrary, we have certain antibodies and anti-viral for Hepatitis B. That is why the outcome for Hepatitis B is much better than Hepatitis C. The recurrence of Hepatitis B after transplantation in the transplanted liver is 11 percent. There used to be an 80 percent chance of recurrence, but due to the discover of the anti-viral and antibodies that are included in the treatment regiment, it lowered the chance of recurrence.
Q: Has liver transplantation ever been done in Kuwait?
A: Liver transplantation has not been done yet in Kuwait. We are on the verge of finalizing an agreement with an American team at the University of Miami. We already approached the team and they have visited Kuwait, but we are just waiting for the final agreement.
The team evaluated the facilities in Kuwait and has pointed out that we should start a liver transplant and liver surgery unit at the Amiri Hospital because, according to their evaluation, the Amiri Hospital has the best facilities such as a new ICU and new operating room to avoid infections in these kinds of cases.
Also, we have Al-Thunayan Gestural and Intestinal Center nearby so if we need intervention by endoscopies it is available.
It has been agreed upon by the heads of departments to locate that unite there and the services have already been opened up, but right now we are only doing specialized cancer surgery and operating on surgical diseases related to the liver, pancreas and the biliary system.
These surgeries have only begun to be performed in Kuwait. We have started doing them around a year ago but now we have a specialized place and a team and we are training the ICU and nursing staff to get used to these kinds of cases. We are getting transfers so far from three or four hospitals, excluding Mubarak Hospital.
We are performing one surgery a week because it is not a very common problem but the problem is still there and we are still new and people are still getting used to us. For example, we don’t get transfers for private hospitals, so we need to build a good reputation.
We have the support of the Ministry of Health because we have ministerial decree to establish the unit and to establish the referral system from other hospitals to this unit. So all these specialty surgeries related to the liver, pancreas and the biliary system are done in our unit.
Q: When do you expect liver transplantation to begin in Kuwait?
A: It depends when we get the agreement. There are certain financial issues not finalized yet, but hopefully by the end of this year or early next year.
Q: How necessary is liver transplantation in Kuwait?
A: It is very necessary and we need it. We are loosing patients and especially young patients who are nationals and non-nationals. The non-nationals have Hepatitis C more frequently and the nationals get Hepatitis B often and there are some cases of cirrhosis of an unknown origin, but it is non-viral and non-alcoholic, it can happen like that because there is an entity called idiopathic, we don’t know the cause. There is a small percentage of alcohol related cases as well.
Kuwait is in need of liver transplantation and we have the facilities to establish this system and if we work hard on deceased donation, we can do 15 to 20 if not more transplantation a year. This may reduce the number of people going outside and this may also reduce the cost. A liver transplantation can cost a person a minimum of one million dollars abroad. Liver transplantation will be free of charge here; the expenses will be for the investigations only.
If the services are provided here, it will reduce the costs and it will be much more effective because we are losing young patients. Recently, only in the l last month, we lost an 18-year-old girl to chemical hepatitis. She took more herbal medication and she developed liver failure. She was put into intensive care and we rushed to send her abroad but we didn’t have enough time. She passed away before we were able to send her abroad.
If we had the liver transplant service here, we could have managed to rescue her. There were also similar cases like this one, we have another 28-year-old lady last year, a mother with three children, who took a medication for TB and had a bad reaction that ended with liver failure. We couldn’t save her live.
So the service has to be established and the MoH is working hard on that. They realized that we needed this. They have the expertise in all different specialties but it is just a matter or organization, plus they wanted an outside experienced team to come here so they will gain the trust of the people.
To be honest, there is a lack of trust in the medical services in Kuwait because of awareness problems and political issues. That is why the Minister of Health Dr Hilal Al-Sayer, made an excellent move by bringing in teams for the chest hospital, the cancer center and the transplant center because these are the three main areas we have not built upon in Kuwait. He provided the teams here so that there will be no excuse for going abroad.
Q: Do you have compiled donor list for liver transplantation?
A: We don’t have a donor list; we should have a recipient list according to blood group because evaluating a person consumes a lot of time and money. We cannot do that unless we reach an agreement and have a starting date. If this process takes longer, I have to evaluate the patient again because his status will change with time.
So if we reach an agreement and decide on a starting date, then we can arrange a list of people who are fit for transplants two months prior by contacting all the centers in Kuwait that deal with liver cirrhosis.
We already have 5,000 people with donation cards and their names are registered in Kuwait Society of Organ Transplantation but we are still working on the deceased donation list.
Any program in the world starts with deceased donation, because it is less complicated than living donation. You have to establish a good deceased donation program before you start a living donor program in case the living donors develop problems themselves or living donor transplantation surgeries go wrong.
Dr Mostafa Al-Mousawi is the head of the organ procurement department which started working toward this program in June and is developing a good system. Now we get a good number of reports from the ICUs, it is just that we need to convince the families to donate.
For example, someone who has had an accident and he is comatose in the ICU. We cannot take consent from him; we have to take consent from his family who may even not be in the country.
So the system is being established, it has been there for a long time and is the best system in the Gulf, but we had some drawbacks due to problems with the transplant coordinators. That is why we are sort of re-evaluating the system and the MOH promised to give us more facilities and to establish more teams.
The American team for liver transplantation will include not only surgeons, but physicians, anesthetists, radiologists and coordinators as well who will train out local coordinators. We will have an agreement to send our Kuwaiti coordinators to Miami to be trained and the non-Kuwaitis will be trained here by the Miami team.
So we will have coordinators with different nationalities to communicate with the families from all over the world, such as Egypt, Syria, India and Bangladesh.
Q: Have there been any unique surgeries done so far for the first time in the Gulf?
A: All what we are doing now is new in the Arabian Gulf and we did one case which was not done before in the ME, but these are not done frequently. We do surgeries for cancer of the liver, pancreas, gal bladder and biliary system or tumor and benign conditions that need surgery.
So far we did eight big surgeries since we started in June. We get referrals from different hospitals and some don’t need surgical intervention for the time being.
The case that we did that was unique is called ‘Synchronous Resection’ where we performed two surgeries at the same time on one patient. This patient had cancer of the colon that has spread to the liver. These surgeries are not frequently done because you need special situations and a dedicated and educated patient that can be aware of the risks.
You also need a two-team approach, a team that can handle the colon cancer and a team which can handle the liver, which was our team. When we evaluated the patient, who is 43 years old, we discovered that she had colon cancer and at the same time she had a big metastatic spread of the tumour to the liver. We decided to do the surgery and the patient had a smooth recovery and she was discharged home by day eight.
It is not the surgeries that matter it is the services that you have around. We had excellent ICU care at the Amiri Hospital, the team was superb. The nursing staff in the operating room was excellent as well. You cannot work alone; you need other services to support you and the patient. I hope in the future we get more referrals from different hospitals.
By: Nihal Sharaf
Source
Curing the incurable becomes a reality
Monday, 16 August 2010 15:00 Dr Nick Walsh .
“You’re negative,” I said and handed her the results. The smile turns to relief, then elation.
Years of living with the virus, six months of difficult treatment, then a six-month wait to see if the virus was completely eradicated.
She strode out of the consultation room and down the corridor clutching the vital result, with a spring in her step and renewed vitality. Along with the hepatitis C virus, the disease was now gone, as was the stigma. Normal life once again.
We live in world full of viruses – some well known, others not, still others awaiting discovery. They range from the irritating common cold to the devastating sociocultural phenomenon that is the human immuno-deficiency virus, or HIV.
The elusive nature of viruses have long defied medical science, none more so than viral hepatitis, which affects nearly half of the world’s population.
More than 500 million people are currently infected with some form of hepatitis.
Compare that with the 42 million worldwide now living with HIV – long considered a more lethal epidemic – and one can begin to grasp the scope and impact of hepatitis.
In addition to causing liver disease, hepatitis is also the most common cause of liver cancer. The virus falls into a series of alphabetical categories, with hepatitis A and B the most common, and treatable, forms.
Hepatitis C was discovered in 1989, and had been referred to prior to its identification simply as non-A, non-B hepatitis.
It is the most elusive and often deadly form of hepatitis, afflicting nearly 170 million people globally and claiming the lives of half a million people each year.
And until the late 1990s, there was no real hope of a cure. Progress has been steady since that time, and in 2010 we can almost refer to hepatitis C as a curable disease.
Just last year, the medical community watched transfixed as the latest drug trials for hepatitis C reported a 75 percent cure rate for a disease that has for so long defied treatment.
Hepatitis C, or HCV, behaves much like HIV by constantly changing to evade attack by the body’s immune system.
Interestingly, the body can clear the virus itself in about 25 percent of cases. This success rate depends on a number of factors, in particular a strong immune system. And unfortunately, up to 75 percent of those exposed to HCV see initial infection become chronic.
The time lag between initial infection and liver failure can be up to 25 years, so HCV remains largely a silent epidemic.
Most infections occur in the developing world, whereas treatment – often costing upwards of US$15,000 or more – is available mostly to people living in the developed world.
Fortunately, treatment for hepatitis C is available in Phnom Penh, and a number of people have already been cured. But the cost puts treatment out of reach for the more than half a million Cambodians living with the virus.
Successful trials have been achieved with a triple regimen of pegylated interferon, which boosts the immune system, and the antiviral drugs ribavirin and telaprevir. This cocktail saw a cure rate of 75 percent in trials reported recently in the New England Journal of Medicine.
A new antiviral drug, boceprevir, has also produced similar results.
Key to successful treatment is to attack the virus at multiple points in its life cycle in order to give the body’s immune system a better chance of destroying it.
The battle to eradicate hepatitis C is fierce, and it has attracted considerable investment by the pharmaceutical sector.
Not surprising, as 4 million Americans and a similar number of Europeans – as well as millions across developing Asia – are potential candidates for treatment.
Medical researchers are looking for the holy grail, a combination of tablets much like treatment for HIV, as well as a shortened treatment cycle, dropping from the current six to 12 months down to three or less.
Cost remains a crucial factor if the developing world is to benefit from recent and forthcoming breakthroughs.
However, greater awareness of the threat of hepatitis C, and now its potential cure, is vital, and community activists have begun the difficult task of spreading the word.
So the once incurable hepatitis C virus has become less elusive and in some cases curable, but like so many other things it depends on where and under what circumstances you live.
In the end, it will be the strength of the community voice to spur continued research and access to treatment that will ultimately help confine hepatitis C to history and save countless lives in the process.
Normal life once again.
Source
“You’re negative,” I said and handed her the results. The smile turns to relief, then elation.
Years of living with the virus, six months of difficult treatment, then a six-month wait to see if the virus was completely eradicated.
She strode out of the consultation room and down the corridor clutching the vital result, with a spring in her step and renewed vitality. Along with the hepatitis C virus, the disease was now gone, as was the stigma. Normal life once again.
We live in world full of viruses – some well known, others not, still others awaiting discovery. They range from the irritating common cold to the devastating sociocultural phenomenon that is the human immuno-deficiency virus, or HIV.
The elusive nature of viruses have long defied medical science, none more so than viral hepatitis, which affects nearly half of the world’s population.
More than 500 million people are currently infected with some form of hepatitis.
Compare that with the 42 million worldwide now living with HIV – long considered a more lethal epidemic – and one can begin to grasp the scope and impact of hepatitis.
In addition to causing liver disease, hepatitis is also the most common cause of liver cancer. The virus falls into a series of alphabetical categories, with hepatitis A and B the most common, and treatable, forms.
Hepatitis C was discovered in 1989, and had been referred to prior to its identification simply as non-A, non-B hepatitis.
It is the most elusive and often deadly form of hepatitis, afflicting nearly 170 million people globally and claiming the lives of half a million people each year.
And until the late 1990s, there was no real hope of a cure. Progress has been steady since that time, and in 2010 we can almost refer to hepatitis C as a curable disease.
Just last year, the medical community watched transfixed as the latest drug trials for hepatitis C reported a 75 percent cure rate for a disease that has for so long defied treatment.
Hepatitis C, or HCV, behaves much like HIV by constantly changing to evade attack by the body’s immune system.
Interestingly, the body can clear the virus itself in about 25 percent of cases. This success rate depends on a number of factors, in particular a strong immune system. And unfortunately, up to 75 percent of those exposed to HCV see initial infection become chronic.
The time lag between initial infection and liver failure can be up to 25 years, so HCV remains largely a silent epidemic.
Most infections occur in the developing world, whereas treatment – often costing upwards of US$15,000 or more – is available mostly to people living in the developed world.
Fortunately, treatment for hepatitis C is available in Phnom Penh, and a number of people have already been cured. But the cost puts treatment out of reach for the more than half a million Cambodians living with the virus.
Successful trials have been achieved with a triple regimen of pegylated interferon, which boosts the immune system, and the antiviral drugs ribavirin and telaprevir. This cocktail saw a cure rate of 75 percent in trials reported recently in the New England Journal of Medicine.
A new antiviral drug, boceprevir, has also produced similar results.
Key to successful treatment is to attack the virus at multiple points in its life cycle in order to give the body’s immune system a better chance of destroying it.
The battle to eradicate hepatitis C is fierce, and it has attracted considerable investment by the pharmaceutical sector.
Not surprising, as 4 million Americans and a similar number of Europeans – as well as millions across developing Asia – are potential candidates for treatment.
Medical researchers are looking for the holy grail, a combination of tablets much like treatment for HIV, as well as a shortened treatment cycle, dropping from the current six to 12 months down to three or less.
Cost remains a crucial factor if the developing world is to benefit from recent and forthcoming breakthroughs.
However, greater awareness of the threat of hepatitis C, and now its potential cure, is vital, and community activists have begun the difficult task of spreading the word.
So the once incurable hepatitis C virus has become less elusive and in some cases curable, but like so many other things it depends on where and under what circumstances you live.
In the end, it will be the strength of the community voice to spur continued research and access to treatment that will ultimately help confine hepatitis C to history and save countless lives in the process.
Normal life once again.
Source
Tackling cancer among poor doesn't have to cost dear
By Kate Kelland
LONDON
Sun Aug 15, 2010 7:04pm EDT
LONDON (Reuters) - The growing burden of cancer in developing countries could be reduced without expensive drugs and equipment, scientists said Monday, but it requires a global effort similar to the fight against HIV/AIDS.
In a study in the Lancet, scientists from the United States, who have formed a Global Task Force on Expanded Access to Cancer Care and Control in Developing Countries (GTF.CCC), said cancer is now a leading cause of death in poor nations but is often neglected in health authorities' prevention and treatment plans.
While only about 5 percent of global resources for cancer are spent in developing countries, the burden of the disease is far greater there than in rich nations, with up to 80 percent of cancer deaths each year occurring in poorer nations.
"Cancer is no longer primarily the burden of high-income countries," the scientists, led by Felicia Knaul of the Harvard Global Equity Initiative, wrote in the study. "The time has come to challenge and disprove the widespread assumption that cancer will remain untreated in poor countries."
They said many cancers that make up the greatest burden in low- and middle-income countries, such as breast cancer, could be treated with drugs that are off-patent and can be manufactured generically at affordable prices.
They cited the breast cancer drug tamoxifen as one example and said that in Malawi, Cameroon and Ghana the total cost of generic chemotherapy drugs with a 50 percent cure rate for a type of cancer called Burkitt's lymphoma could be as low as $50 per patient.
"These drugs should be a focus of cancer treatment programs, rather than expensive on-patent drugs," they wrote.
According to GTF.CCC, rates of cancer in low- and middle-income countries have increased dramatically from 1970, when they accounted for 15 percent of newly reported cancers, to 2008 when that figure rose to 56 percent. The proportion is expected to rise to 70 percent in 2030.
More efforts against smoking, a major risk factor for many cancers which threatens to cause a surge in cancer deaths in Africa in the next decade, would be one relatively cheap way of making an impact, they said, as would increasing awareness about the importance of early cancer detection and screening.
Another intervention with huge potential, they said, would be vaccination against human papillomavirus (HPV), to help prevent cervical cancer, and against hepatitis B virus (HBV), to help prevent liver cancer.
GlaxoSmithKline and Merck & Co make vaccines against HPV and many drugmakers have HBV vaccines but these are often too expensive to be included in the health programs of low- and middle-income countries, the scientists said.
The group criticized what it described as "the public health community's assumption" that cancer could not be treated in poor countries and compared it to "similarly unfounded arguments from more than a decade ago" about treatment for HIV and AIDS.
Major advances in prevention, health services and efforts to bring down drug prices have dramatically increased the number of people in poor countries who have access to HIV treatment.
Knaul's team said like HIV and AIDS, cancer was now "an urgent health and ethical priority" in developing countries.
(Editing by Janet Lawrence)
Source
LONDON
Sun Aug 15, 2010 7:04pm EDT
LONDON (Reuters) - The growing burden of cancer in developing countries could be reduced without expensive drugs and equipment, scientists said Monday, but it requires a global effort similar to the fight against HIV/AIDS.
In a study in the Lancet, scientists from the United States, who have formed a Global Task Force on Expanded Access to Cancer Care and Control in Developing Countries (GTF.CCC), said cancer is now a leading cause of death in poor nations but is often neglected in health authorities' prevention and treatment plans.
While only about 5 percent of global resources for cancer are spent in developing countries, the burden of the disease is far greater there than in rich nations, with up to 80 percent of cancer deaths each year occurring in poorer nations.
"Cancer is no longer primarily the burden of high-income countries," the scientists, led by Felicia Knaul of the Harvard Global Equity Initiative, wrote in the study. "The time has come to challenge and disprove the widespread assumption that cancer will remain untreated in poor countries."
They said many cancers that make up the greatest burden in low- and middle-income countries, such as breast cancer, could be treated with drugs that are off-patent and can be manufactured generically at affordable prices.
They cited the breast cancer drug tamoxifen as one example and said that in Malawi, Cameroon and Ghana the total cost of generic chemotherapy drugs with a 50 percent cure rate for a type of cancer called Burkitt's lymphoma could be as low as $50 per patient.
"These drugs should be a focus of cancer treatment programs, rather than expensive on-patent drugs," they wrote.
According to GTF.CCC, rates of cancer in low- and middle-income countries have increased dramatically from 1970, when they accounted for 15 percent of newly reported cancers, to 2008 when that figure rose to 56 percent. The proportion is expected to rise to 70 percent in 2030.
More efforts against smoking, a major risk factor for many cancers which threatens to cause a surge in cancer deaths in Africa in the next decade, would be one relatively cheap way of making an impact, they said, as would increasing awareness about the importance of early cancer detection and screening.
Another intervention with huge potential, they said, would be vaccination against human papillomavirus (HPV), to help prevent cervical cancer, and against hepatitis B virus (HBV), to help prevent liver cancer.
GlaxoSmithKline and Merck & Co make vaccines against HPV and many drugmakers have HBV vaccines but these are often too expensive to be included in the health programs of low- and middle-income countries, the scientists said.
The group criticized what it described as "the public health community's assumption" that cancer could not be treated in poor countries and compared it to "similarly unfounded arguments from more than a decade ago" about treatment for HIV and AIDS.
Major advances in prevention, health services and efforts to bring down drug prices have dramatically increased the number of people in poor countries who have access to HIV treatment.
Knaul's team said like HIV and AIDS, cancer was now "an urgent health and ethical priority" in developing countries.
(Editing by Janet Lawrence)
Source
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