HIGH-DOSE INTERFERON-ALPHA(2B) TREATMENT PREVENTS CHRONICITY IN ACUTEHEPATITIS-C - A PILOT-STUDY

Acute hepatitis C takes a chronic course in 50-80% of cases. Results w ith interferon treatment are conflicting. To evaluate the efficacy of high-dose interferon treatment, we initiated a pilot study in 1992 usi ng 10 MU interferon-alpha(2b) administered subcutaneously daily until normalization of serum transaminase concentrations. Treatment was begu n when a diagnosis of acute hepatitis C was established. HCV-RNA was t ested using PCR prior to treatment, three times weekly during the firs t two weeks of treatment, and then once weekly until the end of therap y. During the 15-month follow-up, HCV-RNA tests were performed monthly up to month 6 and every two to three months thereafter. Twenty-four p atients were enrolled at the time of writing; age ranged from 18 to 76 years (mean = 32), and nine patients were men. All patients presented with cholestatic hepatitis; 19 were actively abusing intravenous drug s, four had no known parenteral exposure, and one was a medical labora tory technician. All patients were anti-HCV positive, HCV-RNA positive , and HIV negative. Five patients were infected with genotype 3, five with genotype la, five with genotype Ib, three with genotypes 3 and 2, and one with genotypes 1 and 2. All patients exhibited normalized ser um transaminase concentrations within 18-43 days; HCV-RNA became negat ive in all patients within 4-12 days. Toxicity did not exceed grade 1 and disappeared within three days of treatment. In the follow-up perio d, which ranged from six to 29 months (mean = 19.5 +/- 10.4), serum AL T concentrations remained normal and HCV-RNA remained negative in all patients except two dropouts and two patients who developed relapsing disease after having been HCV-RNA negative for three and eight months, respectively. In both patients, the same HCV genotype 3 reemerged. Se rum ALT concentrations ranged from 531 to 1940 IU/liter (mean = 1055; normal < 22). Concentrations of HCV-RNA (Quantiplex; Chiron, Emeryvill e, California) were <3.5 x 10(5) eq/ml in nine of 14 PCR-positive pati ents. In the other five patients, concentrations ranged from 10.4 x 10 (5) eq/ml to 131.6 x 10(5) eq/ml (mean = 69.6 x 10(5)). No correlation was observed between HCV-RNA concentrations and serum ALT concentrati ons at presentation (r = 0.331; P = 0.67) and total dose of interferon -alpha(2b) administered until normalization of ALT (r = -0.088; P = 0. 74). Twenty-two of 24 patients completed treatment (two were noncompli ant). Of these, 20 achieved a complete response (HCV-RNA negative for at least six months). Two of these patients relapsed, and 18 (90%) rem ained HCV-RNA negative for 18.65 (+/-9.7) months. These findings sugge st that high-dose interferon-alpha(2b) is well tolerated and effective in preventing a chronic course of hepatitis C infection.