Jacobson IM
Treatment Options for Patients With Chronic Hepatitis C Not Responding to Initial Antiviral Therapy. [JOURNAL ARTICLE]
Clin Gastroenterol Hepatol 2009 Apr 9.
Pegylated interferon (PEG-IFN) alfa-2a or alfa-2b plus ribavirin (RBV) 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 PEG-IFN alfa used plus the same or higher doses of RBV, switching from one PEG-IFN alfa to the other, increasing the duration of therapy, or using other IFN formulations. Recent studies have demonstrated that SVR can be attained in 10% to 20% of patients retreated with PEG-IFN alfa plus RBV after previous nonresponse to standard IFN plus RBV and in 6% to 8% of prior nonresponders to PEG-IFN plus RBV retreated for 48 weeks. Extending the duration of retreatment to 72 weeks increases SVR rates. Prior relapsers to IFN-based therapy have higher rates of SVR with retreatment than prior nonresponders. Alternatively, the goal of low-dose, maintenance IFN alfa-based therapy is to delay or halt disease progression. Three large studies evaluating alternative treatment strategies in previous nonresponders (Hepatitis C Antiviral Long-term Treatment Against Cirrhosis [HALT-C], Evaluation of PegIntron in Control of Hepatitis C Cirrhosis [EPIC(3)], and Colchicine versus PegIntron Long-term [COPILOT]) have been conducted. Finally, specifically targeted antiviral therapies for hepatitis C have shown promising results in preclinical and early-stage clinical trials when combined with PEG-IFN alfa plus RBV. Novel approaches, including combinations of direct antiviral agents, are needed to achieve major improvements in the treatment of nonresponders.
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