Module Abstract

Strategies for Management of Hepatitis C Treatment Failure

Abstract

This review by Karen L. Lindsay, MD, MMM, explores emerging data from recently completed clinical trials using novel approaches for the retreatment of hepatitis C patients who fail to achieve sustained virologic response (SVR) with an initial course of interferon-based therapy—either nonresponders or responder-relapsers—and discusses potential approaches to managing these patients. A summary of these approaches are as follows:

When the Goal Is Viral Clearance (SVR)

• Recent data confirm clinical factors previously associated with reduced likelihood of SVR on fixed-length peginterferon/ribavirin: HCV genotype, advanced liver disease, and nonadherence.
• These findings underscore the importance of defining the patient’s virologic response pattern, identifying potentially adverse clinical factors, and documenting the treatment adherence profile during a course of interferon-based therapy to design an individualized approach to future retreatment.
• When using peginterferon plus ribavirin therapy, data strongly reinforce the value of treatment courses longer than 48 weeks to prevent virologic relapse in genotype 1 HCV–infected patients who are demonstrating virologic response but do not achieve HCV RNA negativity by treatment Week 12.
• Given the overall low likelihood of viral clearance with peginterferon plus ribavirin retreatment, these data highlight the importance of optimizing clinical factors that improve response and adherence to treatment during initial therapy. Ongoing retreatment trials are evaluating specific antivirals, including triple combination regimens in patients previously treated with peginterferon and ribavirin.

When the Goal Is Delaying Disease Progression

• The HALT-C trial demonstrated that long-term, low-dose peginterferon maintenance therapy for 4 years does not reduce the likelihood of clinical events in HCV-infected patients with advanced fibrosis and clinically compensated liver disease.
• In the COPILOT study, there was no difference in event-free survival between the peginterferon and colchicine treated groups. A subanalysis showed a lower rate of complications of portal hypertension in the peginterferon treated group primarily because of a decreased frequency of variceal bleeding at 2 and 4 years in patients with portal hypertension. Further analysis is needed to determine the frequency of prophylactic treatment for variceal hemorrhage in the study.
• Analyses are under way to determine which patients should be treated with long-term, low-dose peginterferon maintenance therapy.
• Ongoing development of agents aimed at hepatic inflammation and fibrosis may play an important role in the future therapy of patients with advanced liver disease who do not experience viral response or are unable to tolerate peginterferon and ribavirin.