Hepatitis C Treatment Is More Successful before Progression to Advanced Liver Damage

By Liz Highleyman

Interferon-based combination therapy for chronic hepatitis C virus (HCV) infection has a better chance of working if used before the development of advanced liver fibrosis or cirrhosis, according to a study presented at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL 2009) last month in Copenhagen

W.S.C. Cheng from Royal Perth Hospital in Australia and colleagues presented findings from the CHARIOT trial, which evaluated the safety and efficacy of a pegylated interferon induction regimen versus the standard-of-care regimen in people with HCV genotype 1.

This international open-label trial included 896 genotype 1 chronic hepatitis C patients stratified by country and baseline HCV RNA level. Participants were randomized 1:1 to receive either the standard regimen of 180 mcg/week pegylated interferon alfa-2a (Pegasys) for 48 weeks or an induction regimen that started with 360 mcg/week for 12 weeks followed by 180 mcg/week for 36 weeks. All patients also received 1000-1200 mg/day weight-adjusted ribavirin for 48 weeks.

About 70% of participants (n = 641) had baseline liver histology data obtained at study entry. A total of 127 patients (20.3%), with a mean age of about 49 years, had advanced fibrosis or cirrhosis (Metavir stages F3-F4); the remainder, with an mean age of about 43 years, had absent (F0), mild (F1), or moderate (F2) fibrosis.

Results

The sustained virological response (SVR) rate 24 weeks after completion of therapy was considerably lower in patients with advanced fibrosis or cirrhosis.

However, SVR rates were similar in the standard therapy and induction arms, regardless of fibrosis stage:

Stage F3-F4 standard therapy: 24%;
Stage F3-F4 induction regimen: 28%;
Stage F0-F2 standard therapy: 55%;
Stage F0-F2 induction regimen: 58%.

Rapid virological response (RVR) rates at week 4 and early virological response (EVR) rates at week 12 were likewise lower for F3-F4 patients, while HCV relapse rates were higher.

In both the F3-F4 and F0-F2 groups, RVR rates were higher using the induction regimen compared with standard therapy, but the difference diminished with further treatment.

A smaller proportion of patients who experienced RVR went on to achieve SVR in the F3-F4 group compared with the F0-F2 group (67% vs 82%, respectively, with standard therapy; 60% vs 79% with the induction regimen).

The mean cumulative drug doses and the proportion of patients receiving at least 80% or 95% of planned pegylated interferon and ribavirin doses through week 12 were similar in the F3-F4 and F0-F2 groups.

Participants with advanced fibrosis were somewhat more likely to prematurely discontinue treatment for any reason, but the drop-out rate was slightly lower in the induction arms.

Patients with F3-F4 fibrosis were more likely to develop anemia, neutropenia, and thrombocytopenia compared with the F0-F2 group.

However, the frequency of discontinuation due to adverse events, laboratory abnormalities, or death was similar across all groups.

"Patients with advanced fibrosis respond poorly to pegylated interferon and ribavirin therapy," the investigators concluded. "Lower RVR and EVR rates, despite similar early dosing, suggest that differential intrahepatic viral clearance or drug metabolism may partly explain poorer responses."

Royal Perth Hospital, Perth, Australia; Alfred Hospital, Melbourne Australia; Nepean Hospital, Sydney, Australia; Greenslopes Hospital, Brisbane, Australia; Monash Medical Centre, Melbourne, Australia; Royal Prince Alfred Hospital, Australia; SEALS, Prince of Wales Hospital, Sydney, Australia; St. Vincent's Hospital, Melbourne, Australia; Roche Products, Sydney, Australia; Roche, Nutley, NJ; National Centre in HIV Epidemiology and Clinical Research, Sydney, Australia

5/15/09

Reference
WSC Cheng, S Roberts, M Weltman, and others. Efficacy and Safety of Peginterferon Alfa-2a 360 µg/Week in Combination with Ribavirin in Hepatitis C Genotype 1 Patients with Cirrhosis: Analysis from the Chariot Study. 44th Annual Meeting of the European Association for the Study of the Liver (EASL 2009). Copenhagen, Denmark. April 22-26, 2009.

Other Source
Hepatitis Australia. Large scale Australian Hepatitis C Study Shows Need to Treat Sooner. Press release. April 22, 2009.

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15th Conference on Retroviruses and Opportunistic Infections (CROI 2009)
Coverage by HIV and Hepatitis.com - February 8 - 11, 2009, Montreal
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