, Volume 41, Issue 12 Supplement, pp 81S-85S

High-dose interferon-α2b treatment prevents chronicity in acute hepatitis C

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Abstract

Acute hepatitis C takes a chronic course in 50–80% of cases. Results with interferon treatment are conflicting. To evaluate the efficacy of high-dose interferon treatment, we initiated a pilot study in 1992 using 10 MU interferon-α2b administered subcutaneously daily until normalization of serum transaminase concentrations. Treatment was begun when a diagnosis of acute hepatitis C was established. HCV-RNA was tested using PCR prior to treatment, three times weekly during the first two weeks of treatment, and then once weekly until the end of therapy. 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 patients 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 drugs, four had no known parenteral exposure, and one was a medical laboratory technician. All patients were anti-HCV positive, HCV-RNA positive, and HIV negative. Five patients were infected with genotype 3, five with genotype 1a, five with genotype 1b, three with genotypes 3 and 2, and one with genotypes 1 and 2. All patients exhibited normalized serum transaminase concentrations within 18–43 days; HCV-RNA became negative in all patients within 4–12 days. Toxicity did not exceed grade 1 and disappeared within three days of treatment. In the follow-up period, which ranged from six to 29 months (mean=19.5±10.4), serum ALT 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. Serum ALT concentrations ranged from 531 to 1940 IU/liter (mean=1055; normal <22). Concentrations of HCV-RNA (Quantiplex; Chiron, Emeryville, California) were <3.5×105 eq/ml in nine of 14 PCR-positive patients. In the other five patients, concentrations ranged from 10.4×105 eq/ml to 131.6×105 eq/ml (mean=69.6×105). No correlation was observed between HCV-RNA concentrations and serum ALT concentrations at presentation (r=0.331;P=0.67) and total dose of interferon-α2b administered until normalization of ALT (r=−0.088;P=0.74). Twenty-two of 24 patients completed treatment (two were noncompliant). Of these, 20 achieved a complete response (HCV-RNA negative for at least six months). Two of these patients relapsed, and 18 (90%) remained HCV-RNA negative for 18.65 (±9.7) months. These findings suggest that high-dose interferon-α2b is well tolerated and effective in preventing a chronic course of hepatitis C infection.