Update on Hepatitis C Treatment

, Clinical Instructor, UCLA School of Medicine, Los Angeles, California, and , Medical Director, Liver Transplantation, Cedars-Sinai Medical Center, Associate Professor of Medicine, UCLA School of Medicine, Los Angeles, California

Disclosures

February 15, 2001

In This Article

Combination Therapy

A significant improvement in SR resulted from the addition of ribavirin to standard IFN-alfa. Ribavirin, a guanosine analogue, was initially evaluated as monotherapy for chronic HCV because of its antiviral activity against other RNA viruses.[11,12,13] Although as monotherapy it reduces ALT levels, it does not appear to have a direct antiviral effect and fails to lower serum HCV RNA levels. Moreover, results of most studies with ribavirin have found no improvement in hepatic histology, although a longer 2-year treatment regimen was shown to reduce necroinflammatory activity.[13]

However, in combination with IFN-alfa 2b, ribavirin leads to a significant increase in SR in treatment-naive patients.[14] SRs of 31% with 24 weeks and 38% with 48 weeks of combination therapy were achieved vs 6% with 24 weeks and 13% with 48 weeks of IFN monotherapy.[14] In relapsers, enhanced SR rates also occur on retreatment using combination therapy, from 30% to 49%; in prior NRs, SR of 14% has been reported with 6 months of combination therapy.[15,16]

Histologic improvement was more common among treatment-naive patients treated with combination therapy.[14] Similar improvement was found in a randomized controlled trial of treatment-relapse patients.[15]

However, the improved SR rates observed with combination therapy are also associated with more expense and an increased frequency of adverse effects compared with IFN-alfa monotherapy.[14] Dose-related hemolytic anemia is a particular concern with ribavirin[11,13] as is teratogenicity, based on animal studies.[16] The mean drop in hemoglobin in patients treated with combination therapy is between 2 and 3 g/dL, although a fall of more than 4 g/dL has been observed in about 10% of patients. The anemia may be poorly tolerated in patients with ischemic heart disease in particular as treatment is extended to older patients.[17] Accumulation of ribavirin metabolites that are not cleared by dialysis occurs in end-stage renal disease.(18)

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