Peginterferon maintenance therapy does not improve progression in HCV

Patients with chronic hepatitis C virus (HCV) infection who have not responded to previous treatment with pegylated interferon alfa-2a (peginterferon) and ribavirin do not demonstrate a reduced rate of disease progression when they undergo long-term treatment with pegylated interferon alfa-2a compared with untreated patients. These results were published in the New England Journal of Medicine.

In the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial, patients were included if they demonstrated lack of a sustained virologic response to previous therapy, advanced hepatic fibrosis, and no history of hepatic decompensation or hepatocellular carcinoma. During the lead-in phase, all patients were treated with subcutaneous (SC) pegylated interferon alfa-2a 180 mcg/wk and oral ribavirin 1,000 to 1,200 mg/d (based on weight) for at least 24 weeks before randomization. Patients with no response (defined as at least 1 log₁₀ IU per mL decrease in HCV RNA level from baseline) at 20 weeks were randomized to either 3.5 years of treatment with pegylated interferon alfa-2a 90 mcg/wk without ribavirin or no treatment (control group). The primary outcome was the progression of liver disease (indicated by death, hepatic decompensation, hepatocellular carcinoma, a Child-Turcotte-Pugh score of 7 or more on 2 consecutive study visits, or an increase in the Ishak hepatic fibrosis score of at least 2 points).

A total of 1,050 patients were randomized; 517 received treatment with pegylated interferon alfa-2a and 533 received no treatment for 3.5 years. Baseline demographics were similar between groups. In treated patients, serum alanine aminotransferase levels and serum HCV RNA levels decreased significantly versus untreated patients at 3.5 years (P
The authors stated that their findings “contradict the results of several previous studies, but those studies either were not prospective, randomized trials or relied on end points other than clinical outcomes.” The current results led them to conclude that “long-term maintenance therapy with half-dose peginterferon is ineffective in preventing clinical and histologic disease progression and is not indicated in patients with hepatitis C-associated advanced fibrosis, without or without cirrhosis, who have not had a response to a standard course of peginterferon and ribavirin therapy.”

Source
Di Bisceglie AM, Shiffman ML, Everson GT, et al; for the HALT-C Trial Investigators. Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon. N Engl J Med. 2008;359:2429-2441.