Treatment of chronic hepatitis C in patients who failed interferon monotherapy: Effects of higher doses of interferon and ribavirin combination therapy

OBJECTIVE: The present study was designed to evaluate the effectiveness of interferon-ribavirin combination therapy for treatment of chronic hepatitis C virus (HCV) in patients who failed previous treatment with interferon mo notherapy. METHODS: A total of 140 patients with well-documented chronic HCV who faile d to achieve a virological (if HCV-RNA was assessed) or biochemical respons e (if HCV-RNA was not assessed) to interferon monotherapy, 3 mU three times weekly (TIW) for 3-18 months, were randomly assigned to one of three treat ment groups. Group A patients were treated with 5 mU interferon TIW for 6 m onths. Ribavirin (1000-1200 mg daily) was added in those patients HCV-RNA p ositive at month 3. Group B patients were treated with 3 mU interferon TIW plus ribavirin (1000-1200 mg daily) for 6 months. The dose of interferon wa s increased to 5 mU TIW in those patients HCV-RNA positive at month 3. Grou p C patients were treated with 5 mU interferon TIW plus ribavirin (1000-120 0 mg daily) for 6 months. Serum ALT and HCV-RNA were monitored during and a fter treatment for a total of 15 months. RESULTS: Seventeen percent of patients in group A became HCV-RNA negative b y treatment month 3. Adding ribavirin resulted in one additional patient be coming HCV-RNA negative. However, none of the patients in this group achiev ed sustained virological response. Twenty-six percent of patients in group B became HCV-RNA negative by treatment month 3. Increasing the dose of inte rferon from 3 to 5 mU TIW increased virological response to 30%. However, s ustained virological response was observed in only 14%. Thirty percent of p atients in group C became HCV-RNA negative, but sustained virological respo nse was observed in only 12%. Sustained virological response was found to b e significantly greater in patients with a nontype 1 HCV genotype (p < 0.00 2) and in patients who had a decline in HCV-RNA titer to a value <100,000 c opies/ml during their previous course of interferon monotherapy (p < 0.0001 ). None of the 12 sustained responders were African Americans (p < 0.013). CONCLUSIONS: Retreatment of nonresponders with interferon-ribavirin combina tion therapy results in limited benefit; only 13% of patients achieved sust ained virological response. Response was extremely poor in African American s and those with HCV genotype 1. (Am J Gastroenterol 2000; 95:2928-2935. (C ) 2000 by Am. Coll. of Gastroenterology).