November 26, 2010

Specialists Boost HCV Treatment Rates in Veterans

By Dave Levitan

NEW YORK (Reuters Health) Nov 23 - HCV treatment rates are low among veterans, but consultation with a specialist can drastically increase the likelihood of therapy.

"The study supports previous findings of low treatment rates reported in single or few centers in the VA, and extends the findings to the entire national VA system," said the new study's lead author Dr. Jennifer Kramer, of the Michael E. DeBakey Veterans Affairs Medical Center in Houston, in an e-mail to Reuters Health.

Dr. Kramer and colleagues used retrospective data from the Veterans Affairs hepatitis C virus Clinical Case Registry to evaluate 29,695 patients diagnosed with the virus between 2003 and 2004. Overall, only 4,213 patients (14.2%) received treatment. The study's results were published online ahead of print November 9th in the American Journal of Gastroenterology.

Several patient, provider and facility-related factors influenced whether or not a patient received treatment. Black patients had an adjusted odds ratio for receiving treatment of 0.52 compared with white patients (p<0.0001). Patients older than 65 also had a significantly lower chance of being treated (OR, 0.32; p<0.0001) compared to those under 45 years, as did male patients (OR, 0.53; p<0.0001).

Patients with cirrhosis were significantly more likely to receive treatment (OR, 2.11; p<0.0001), and those with alcohol or other drug abuse, anxiety, post-traumatic shock disorder or severe depression were less likely.

"According to our findings, seeing a specialist consultant was the most important predictor for receipt of hepatitis C virus treatment," Dr. Kramer said, with an OR of 9.34.

"Clinical reminders for timely referral and the availability of adequate capacity of trained specialists are some of the basic needs for managing this disease."

Dr. Kramer said that the generally low treatment rates in the VA system could be improved by interventions targeting factors that are considered as barriers to treatment; these include depression and alcohol abuse. Her group is in the early stages of a new study of a "collaborative depression management" program in four VA hospitals that Dr. Kramer hopes will help remove one of the modifiable barriers to hepatitis C treatment.

Am J Gastroenterol. Posted online November 9, 2010. Abstract


Induction Immunosuppression Improves Long-Term Graft and Patient Outcome in Organ Transplantation: An Analysis of United Network for Organ Sharing Registry Data

Transplantation. 2010 Nov 4. [Epub ahead of print]

Cai J, Terasaki PI.

Terasaki Foundation Laboratory, Los Angeles, CA.


BACKGROUND.: Induction agents have been shown to reduce the rate of acute rejection. They have not been clearly shown to improve graft and patient survival. METHODS.: United Network for Organ Sharing registry data were analyzed to show the status of induction therapy in the United States and to determine the effect of induction therapy on long-term graft and patient survival. RESULTS.: Since establishment of the United Network for Organ Sharing renal transplant registry, there have been three distinct eras of induction regimen: (1) the low-induction, old antibody era, 1987 to 1993, when antilymphocyte globulin and muromonab-CD3 were the major agents; (2) a high-induction, transitional era, 1994 to 2002, when basiliximab (1998), daclizumab (1998), and rabbit antithymocyte globulin (rATG; 1999) replaced antilymphocyte globulin and muromonab-CD3, with maintenance agents also used; (3) the high-induction, modern antibody era, 2003 to present, with most patients receiving rATG, basiliximab, daclizumab, or alemtuzumab (2003). Induction recipients had higher graft and patient survival rates than nonrecipients in all categories of organ transplant. The improvement was statistically significant in kidney, liver, and lung transplants, although liver and lung recipients had a lower percentage of patients receiving induction than did kidney patients. Kidney transplant recipients on alemtuzumab with steroids had the lowest risk of graft failure, followed by those on alemtuzumab alone, rATG with steroids, rATG alone, and then basiliximab with steroids. Improvement was not statistically significant with daclizumab (alone or with steroids), basiliximab alone, or steroids alone. CONCLUSION.: Induction immunosuppression improved graft and patient outcome for most organ transplants. Depleting agents (alemtuzumab and rATG)-especially in combination with steroids-seem to be more efficient in preventing renal graft failure than nondepleting agents (basiliximab and daclizumab).

PMID: 21057388 [PubMed - as supplied by publisher]


Role of the EASL, RECIST, and WHO response guidelines alone or in combination for hepatocellular carcinoma: Radiologic–pathologic correlation

Articles in Press

Ahsun Riaz 1, Khairuddin Memon 1, Frank H. Miller 1, Paul Nikolaidis 1, Laura M. Kulik 2, Robert J. Lewandowski 1, Robert K. Ryu 1, Kent T. Sato 1, Vanessa L. Gates 1, Mary F. Mulcahy 3, Talia Baker 4, Ed Wang 5, Ramona Gupta 1, Ritu Nayar 6, Al B. Benson III 3, Michael Abecassis 4, Reed Omary 1, Riad Salem 14

Received 15 February 2010; received in revised form 1 October 2010; accepted 6 October 2010. published online 26 November 2010.
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Background & Aims
We sought to study receiver-operating characteristics (ROC) of the European Association for the Study of the Liver (EASL), Response Evaluation Criteria in Solid Tumors (RECIST), and World Health Organization (WHO) guidelines for assessing response following locoregional therapies individually and in various combinations.

Eighty-one patients with hepatocellular carcinoma underwent liver explantation following locoregional therapies. Response was assessed using the EASL, RECIST, and WHO. Kappa statistics were used to determine inter-method agreement. Uni/multivariate logistic regression analyses were performed to determine the variables predicting complete pathologic necrosis. Numerical values were assigned to the response classes: complete response=0, partial response=1, stable disease=2, and progressive disease=3. Various mathematical combinations of the EASL and WHO were tested to calculate scores and their ROCs were studied using pathological examination of the explant as the gold standard.

Median times (95% CI) to the WHO, RECIST, and EASL responses were 5.3 (4–11.5), 5.6 (4–11.5), and 1.3months (1.2–1.5), respectively. Kappa coefficients for WHO/RECIST, WHO/EASL, and RECIST/EASL were 0.78, 0.28, and 0.31, respectively. EASL response demonstrated significant odds ratios for predicting complete pathologic necrosis on uni/multivariate analyses. Calculated areas under the ROC curves were: RECIST: 0.63, WHO: 0.68, EASL: 0.82, EASL+WHO: 0.82, EASL×WHO: 0.85, EASL+(2×WHO): 0.79 and (2×EASL)+WHO: 0.85. An EASL×WHO Score of 1 had 90.2% sensitivity for predicting complete pathologic necrosis.

The product of WHO and EASL demonstrated better ROC than the individual guidelines for assessment of tumor response. The EASL×WHO scoring system provides a simple and clinically applicable method of response assessment following locoregional therapies for hepatocellular carcinoma.

Keywords: Hepatocellular carcinoma, Locoregional therapies, Imaging, Pathologic correlation

1 Department of Radiology, Northwestern University, Chicago IL, USA
2 Department of Medicine, Division of Hepatology, Northwestern University, Chicago, IL, USA
3 Department of Medicine, Division of Medical Oncology, Northwestern University, Chicago, IL, USA
4 Department of Surgery, Division of Transplant Surgery, Northwestern University, Chicago, IL, USA
5 Department of Surgery, Section of Biostatistics, Northwestern University, Chicago, IL, USA
6 Department of Pathology, Northwestern University, Chicago, IL, USA

Corresponding author. Address: Interventional Oncology, Department of Radiology, 676N, St. Clair, Suite 800, Chicago, IL 60611, USA. Tel.: +1 312 695 6371; fax: +1 312 695 0654.

PII: S0168-8278(10)00910-4
© 2010 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.


IL-28B rs12979860 C/T allele distribution in patients with liver cirrhosis: Role in the course of chronic viral hepatitis and the development of HCC

Articles in Press

Carlo Fabris 1, Edmondo Falleti 2, Annarosa Cussigh 2, Davide Bitetto 1, Elisabetta Fontanini 2, Sara Bignulin 1, Sara Cmet 2, Ezio Fornasiere 1, Elisa Fumolo 1, Stefano Fangazio 3, Andrea Cerutti 3, Rosalba Minisini 3, Mario Pirisi 3, Pierluigi Toniutto 1

Received 23 January 2010; received in revised form 8 July 2010; accepted 17 July 2010. published online 26 November 2010.
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Background & Aims
A single nucleotide polymorphism (rs12979860 C/T) 3kb upstream of the interleukin 28B (IL-28B) gene was shown to be associated with hepatitis C clearance. We verified whether this association also translates into a different genotype distribution at the end of the disease trajectory.

A RFLP-PCR technique was used to genotype 412 patients with cirrhosis due to hepatitis C (n=199), hepatitis B (n=75), alcohol (n=110) and other causes (n=28), of whom 256 underwent liver transplantation (OLT). Hepatocellular carcinoma (HCC) was demonstrated in the native liver of 85 OLT patients, 52 with viral cirrhosis, and 33 with non-viral cirrhosis. A group of 292 patients (235 HCV and 57 HBV positive) with mild chronic hepatitis and 344 healthy subjects served as controls.

A significant difference (p=0.0005) was observed in IL-28B rs12979860 genotype frequencies between patients with viral cirrhosis (C/C=99, C/T=137, T/T=38) and those with non-viral cirrhosis (C/C=72, C/T=58, T/T=8). Patients with HCV related cirrhosis carried more frequently the T/T genotype in comparison to mild hepatitis C or HBV-related cirrhosis. IL-28B rs12979860 genotype frequencies were C/C=23, C/T=50, T/T=12 among OLT patients with cirrhosis complicated by HCC, and C/C=79, C/T=78, T/T=14 among patients with cirrhosis not complicated by HCC (p<0.005).

IL-28B rs12979860 C/T polymorphism T allele is more prevalent in patients with viral cirrhosis due to HCV in comparison to other aetiologies and to patients with mild chronic hepatitis C. Among OLT patients, carriage of this allele seems to augment the risk of developing HCC.

Keywords: Interleukin 28B, Hepatitis C, Liver cirrhosis, Hepatocellular carcinoma, Genetic polymorphisms

Abbreviations: HBV, hepatitis B virus, HCV, hepatitis C virus, HCC, hepatocellular carcinoma, IFN, interferon, SVR, sustained viral response, IL, interleukin, OLT, liver transplantation

1 Medical Liver Transplantation Unit, Internal Medicine, DPMSC, University of Udine, Italy
2 Laboratory Medicine, University of Udine, Italy
3 Department of Clinical and Experimental Medicine, University of Eastern Piedmont “A. Avogadro”, Novara, Italy

Corresponding author. Address: Internal Medicine, Medical Liver Transplantation Unit, University of Udine, Piazzale S.M. Della Misericordia 1, 33100 Udine, Italy. Tel.: +39 0432559802; fax: +39 043242097.

PII: S0168-8278(10)00807-X
© 2010 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.


Etiology-related determinants of liver stiffness values in chronic viral hepatitis B or C

Articles in Press

Mirella Fraquelli 1, Cristina Rigamonti 2, Giovanni Casazza 3, Maria Francesca Donato 2, Guido Ronchi 2, Dario Conte 1, Mariagrazia Rumi 2, Pietro Lampertico 2, Massimo Colombo 2

Received 22 January 2010; received in revised form 23 July 2010; accepted 23 July 2010. published online 26 November 2010.
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Background & Aims
Transient elastography (TE) has gained popularity for the non-invasive assessment of severity of chronic viral hepatitis, but a comprehensive evaluation of the factors that might account for discrepancy in diagnostic accuracy between TE and the standard of care liver biopsy (LB) is still needed.

Patients with chronic hepatitis-B (HBV, n=104) or -C (HCV, n=453) underwent percutaneous LB concomitantly with TE (FibroScan®; Echosens, Paris, France). Liver cell necroinflammatory activity (A) and fibrosis (F) were assessed by METAVIR. Perisinusoidal fibrosis was rated with a 0–3 score. Determinants of TE results were investigated by a linear regression model whereas discordance between TE and LB results was assessed by logistic regression.

Fibrosis (p<0.0001) and liver cell necroinflammatory activity (p<0.0001) were independently associated with TE results in both HBV and HCV patients, whereas steatosis (p<0.0001) was independently associated with TE in HCV only. Fibrosis overestimation was predicted by severe/moderate necroinflammatory activity in HBV and by older age (41–60 or>60years vs.<40), >2 UNL AST and>2 UNL GGT, as well as severe/moderate necroinflammatory activity and severe/moderate steatosis in HCV. In the latter patients, however, moderate/severe necroinflammatory activity and steatosis were the only independent predictors of fibrosis overestimation.

Fibrosis and necroinflammatory activity are the main determinants of TE in chronic viral hepatitis. Since TE staging of Fibrosis is influenced by necroinflammatory activity and steatosis, a diagnostic LB is deemed necessary for a reliable intra-patient TE monitoring of the course of viral hepatitis.

Abbreviations: TE, transient elastography, LB, liver biopsy, CLD, chronic liver disease, A, necroinflammatory activity, F, fibrosis stage, BMI, body mass index, HBV, hepatitis B virus, HCV, hepatitis C virus, ALT, alanine aminotransferase, AST, aspartate aminostransferase, GGT, gamma-glutamyltranspeptidase, HBsAg, hepatitis B surface antigen, US, ultrasound, kPa, kilopascal, IQR, interquartile range, UNL, upper normal limit, OR, odds ratio, 95% CI, 95% confidence interval

Keywords: Transient elastography, Liver biopsy, Liver fibrosis, Hepatitis B, Hepatitis C

1 Second Division of Gastroenterology, IRCCS Fondazione Policlinico, Mangiagalli e Regina Elena, Milano, Italy
2 First Division of Gastroenterology, IRCCS Fondazione Policlinico, Mangiagalli e Regina Elena, Milano, Italy
3 Department of Statistic and Biometry, University of Milan, Milano, Italy

Corresponding author. Address: Second Division of Gastroenterology, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milano, Italy. Tel.: +39 02 55033445; fax: +39 02 55033644.

PII: S0168-8278(10)00805-6
© 2010 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.