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 were 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.
Subject(s)
Antiviral Agents/administration & dosage , Carcinoma, Hepatocellular/prevention & control , Hepatitis C, Chronic/drug therapy , Interferon-alpha/administration & dosage , Liver Cirrhosis/drug therapy , Liver Neoplasms/prevention & control , Polyethylene Glycols/administration & dosage , Antiviral Agents/adverse effects , Biomarkers/blood , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/virology , Disease Progression , Drug Administration Schedule , Europe , Female , Hepacivirus/genetics , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/mortality , Humans , Hypertension, Portal/drug therapy , Hypertension, Portal/virology , Interferon alpha-2 , Interferon-alpha/adverse effects , Kaplan-Meier Estimate , Liver Cirrhosis/diagnosis , Liver Cirrhosis/mortality , Liver Cirrhosis/virology , Liver Neoplasms/mortality , Liver Neoplasms/virology , Male , Middle Aged , North America , Patient Selection , Polyethylene Glycols/adverse effects , Proportional Hazards Models , Prospective Studies , RNA, Viral/blood , Recombinant Proteins , Risk Assessment , Risk Factors , South America , Time Factors , Treatment Outcome , Viral LoadABSTRACT
The major hepatological consequence of HCV infection is the progression to cirrhosis and its potential complications. Several factors have been clearly shown to be associated with fibrosis progression rate: duration of infection, age, male sex, consumption of alcohol, HIV coinfection and low CD4 count. As age and duration of infection increases, the risk of fibrosis increases and the impact of treatment (IFN) decreases. In conclusion, fibrosis progression has a progressive acceleration, sex, age and consumption of alcohol are strongly involved in this progression; the possibility to assess with non-aggressive biochemical markers the fibrosis stage will probably allow in the future to identify other factors related to fibrosis progression.