The Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial (HALT-C)

General Description

The Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial (HALT-C) was a randomized clinical trial of long-term use of peginterferon alfa-2a in patients with chronic hepatitis C. The study investigated whether long-term antiviral therapy could prevent progressive liver disease—including cirrhosis, liver failure, hepatocellular carcinoma, and death—in chronic hepatitis C participants. Participants with chronic hepatitis C and advanced fibrosis who failed to respond to prior treatment with peginterferon and ribavirin were enrolled in the study. The participants, who were stratified according to stage of fibrosis, were randomly assigned to receive either peginterferon or no therapy for 3.5 years. The primary outcome measure was progression of liver disease, as indicated by death, hepatocellular carcinoma, hepatic decompensation, or, for those with bridging fibrosis at baseline, an increase in the Ishak fibrosis score of 2 or more points. Results showed that the level of serum aminotransferases, the level of serum hepatitis C virus RNA, and histologic necroinflammatory scores all decreased significantly with treatment, but there was no significant difference between the groups in the rate of disease progression.

Some of the patients with hepatitis C-related advanced liver disease developed hepatocellular carcinoma (HCC), and there is an existing matched set of samples from these patients and controls. Please see the HCC Documents detailing the description of this set of samples and guidelines for its use in validating serum biomarkers. Investigators interested in using this set should make sure to refer to it specifically in their requests.

Objectives

The HALT-C study sought to determine if long-term interferon therapy over several years suppresses the hepatitis C virus and prevents progression to cirrhosis and liver cancer in patients with chronic hepatitis C.

Outcome Measure

The primary outcome measure was progression of liver disease, as indicated by death, hepatocellular carcinoma, hepatic decompensation, or, for those with bridging fibrosis at baseline, an increase in the Ishak fibrosis score of 2 or more points. Serious adverse events, events requiring dose reductions, and quality of life were measured as secondary outcomes.

Criteria

Participants of at least 18 years of age who met the following criteria were enrolled:

• Positive for hepatitis C

• Previous treatment with any interferon or interferon and ribavirin for at least 3 months

• Documented non-response to treatment with interferon

• Liver biopsy demonstrating significant liver scarring

Patients with other liver diseases, unstable major medical diseases or conditions, major complications of cirrhosis, and recent abuse of alcohol and/or illicit drugs were excluded.

Outcome

The HALT-C study showed that long-term therapy with peginterferon did not reduce the rate of disease progression in patients with chronic hepatitis C and advanced fibrosis, with or without cirrhosis, who did not have a response to initial treatment with peginterferon and ribavirin.