Treatment Options for Patients With Chronic Hepatitis C Not Responding to Initial Antiviral Therapy

Pegylated interferon alfa-2a or alfa-2b plus ribavirin for 24 or 48 weeks, depending on genotype, is the standard of care for patients with chronic hepatitis C. However, up to 50% of patients are nonresponsive or experience relapse after treatment ends. Consequently, effective retreatment approaches for this population are urgently needed. Retreatment strategies aimed at viral eradication have included retreatment with the same or higher doses of the first pegylated interferon alfa used plus the same or higher doses of ribavirin, switching from one pegylated interferon alfa to the other, increasing the duration of therapy, or using other interferon formulations. Recent studies have demonstrated that sustained virologic response can be attained in 10% to 20% of patients retreated with pegylated interferon alfa plus ribavirin after previous nonresponse to standard interferon plus ribavirin and in 6% to 8% of prior nonresponders to pegylated interferon plus ribavirin retreated for 48 weeks. Extending the duration of retreatment to 72 weeks increases sustained virologic response rates. Prior relapsers to interferon-based therapy have higher rates of sustained virologic response with retreatment than prior nonresponders. Three large multicenter studies evaluating the capacity of long-term, low-dose, maintenance interferon-based therapy to delay or halt disease progression have been conducted, demonstrating no significant impact on overall clinical outcomes in the intent-to-treat analyses. Finally, specifically targeted antiviral therapies for hepatitis C have shown promising results in preclinical and early-stage clinical trials when combined with pegylated interferon alfa plus ribavirin. Novel approaches, including combinations of direct antiviral agents, are needed to achieve major improvements in the treatment of nonresponders.

Abbreviations used in this paper: Alb-IFN, albinterferon, CIFN, consensus interferon, DIRECT, Daily-Dose Consensus Interferon and RBV: Efficacy of Combined Therapy, EPIC³, Evaluation of PegIntron in Control of Hepatitis C Cirrhosis, FDA, Food and Drug Administration, G1, genotype 1, G2, genotype 2, G3, genotype 3, HALT-C, Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis, HCC, hepatocellular carcinoma, HCV, hepatitis C virus, IFN, interferon, PEG-IFN, pegylated interferon, RBV, ribavirin, SVR, sustained virologic response, STAT-C, specifically targeted antiviral therapies for hepatitis C, COPILOT, Colchicine versus PegIntron Long-term