ASSESSMENT WITH MAINTENANCE INTERFERON IN PATIENTS WITH CHRONIC HEPATITIS C

EASL; Session Title: Category 08b: Viral Hepatitis C: Clinical (except therapy)


Presentation Date: 02 APR, 2011

WHAT IS THE MOST ACCURATE METHOD FOR EVALUATING CHANGES IN FIBROSIS? ASSESSMENT WITH MAINTENANCE INTERFERON IN PATIENTS WITH CHRONIC HEPATITIS C

P. Calès1*, J.-P. Zarski2, C. Michelet3, S. Bertrais4, N. Sturm2, J.-M. Chapplain3, G. Babany5, M. Eddine Charaf5


Background and aims: Maintenance interferon has not been evaluated in patients with chronic hepatitis C, non responders to standard of care, with various degrees of fibrosis stages. Moreover, precise diagnostic means of liver fibrosis, including liver morphometry and quantitative non-invasive blood tests, have not been evaluated in this clinical setting. Our main aim was to evaluate whether quantitative measurements of liver fibrosis outperform histological staging in detecting natural or interferon-induced changes.

Methods: We compared Metavir fibrosis (F) staging and activity grading, morphometry (area and fractal dimension of fibrosis) and 6 blood tests in 157 patients with chronic hepatitis C from two randomized trials testing maintenance interferon for 96 weeks.

Results: Paired liver biopsies and blood tests were available for 101 patients. Treatment effects: there was a significant improvement in Metavir activity grade and a significant decline in FibroMeters specific for cirrhosis and area of fibrosis in the interferon group vs. controls. All relative changes (%) in histological characteristics were significantly greater in F1 vs. other F stages only in the interferon group. Course between measurements at week 0 and 96 in the whole population: dynamic sensitivity: there was a significant progression in area of fibrosis (p=0.026), FibroMeter for significant fibrosis (p=0.020) and cirrhosis (p=0.003) but not with other diagnostic means. Dynamic reproducibility: agreement was good (ric ≥0.72) for Metavir fibrosis score, and for FibroMeters for significant fibrosis, cirrhosis and area of fibrosis. Among histological characteristics, the relative change (%) in area of fibrosis was significantly higher than that of fibrosis fractal dimension (p=0.003) or Metavir fibrosis score (p=0.015). FibroMeter for cirrhosis was the only blood test with a change significantly higher than that of area of fibrosis (p=0.039).

Conclusion: Area of fibrosis by morphometry and blood tests, reflecting fibrosis quantity, have excellent dynamic sensitivity and/or dynamic reproducibility in detecting small changes in liver fibrosis. FibroMeter for cirrhosis has more dynamic sensitivity and reproducibility than area of fibrosis by morphometry. The study also shows that maintenance interferon does not improve fibrosis whatever its stage even with precise quantitative diagnostic methods.

http://www1.easl.eu/easl2011/program/Posters/Abstract1022.htm
 
 
Maintenance Therapy With Peginterferon Alfa-2b Does Not Prevent Hepatocellular Carcinoma in Cirrhotic Patients With Chronic Hepatitis C


Gastroenterology. 2011 Mar 16.
Bruix J, Poynard T, Colombo M, Schiff E, Burak K, Heathcote EJ, Berg T, Poo JL, Mello CB, Guenther R, Niederau C, Terg R, Bedossa P, Boparai N, Griffel LH, Burroughs M, Brass CA, Albrecht JK; EPIC(3) Study Group.

BCLC Group; Liver Unit, Hospital Clinic of Barcelona, University of Barcelona; IDIBAPS, Centro de Investigación Biomédica en Red de Hepatología y Enfermedades Digestivas, Barcelona, Spain.

Abstract

BACKGROUND & AIMS: Several studies have reported that low doses of interferon can delay the development of hepatocellular carcinoma (HCC) and progression of chronic hepatitis C. We investigated the incidence of clinical events among participants of the Evaluation of PegIntron in Control of Hepatitis C Cirrhosis (EPIC(3)) program.

METHODS: Data was analyzed from an open-label randomized study of patients with chronic hepatitis C who had failed to respond to interferon alfa plus ribavirin. All patients had compensated cirrhosis with no evidence of HCC. Patients received peginterferon alfa-2b (0.5 μg/kg/week; n = 311) or no treatment (controls, n = 315) for a maximum period of 5 years, or until 98 patients had a clinical event (hepatic decompensation, HCC, death, or liver transplantation). The primary measure of efficacy was time until the first clinical event.

RESULTS: There was no significant difference in time to first clinical event among patients who received peginterferon alfa-2b, compared with controls (hazard ratio [HR], 1.452; 95% confidence interval [CI], 0.880-2.396). There was no decrease in the development of HCC with therapy. The time to disease progression (clinical events or new or enlarged varices) was significantly longer for patients who received peginterferon alfa-2b, compared with controls (HR, 1.564; 95% CI, 1.130-2.166). In a prospectively defined subanalysis of patients with baseline portal hypertension, peginterferon alfa-2b significantly increased the time to first clinical event, compared with controls ( P =.016). There were no new safety observations.

CONCLUSIONS: Maintenance therapy with peginterferon alfa-2b is not warranted in all patients and does not prevent HCC. However, there is a potential clinical benefit of long-term suppressive therapy in patients with preexisting portal hypertension.

Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.
PMID: 21419770 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/21419770