title: High-dose interferon-alpha2b treatment prevents chronicity in acute hepatitis C: a pilot study.
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-alpha2b 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 x 10(5) eq/ml in nine of 14 PCR-positive patients. 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 concentrations at presentation (r = 0.331; P = 0.67) and total dose of interferon-alpha2b 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-alpha2b is well tolerated and effective in preventing a chronic course of hepatitis C infection.
authors.affiliation: Department of Internal Medicine, Innsbruck University, Austria.
authors.forename: W
authors.initials: W
authors.lastname: Vogel
authors.forename: I
authors.initials: I
authors.lastname: Graziadei
authors.forename: F
authors.initials: F
authors.lastname: Umlauft
authors.forename: C
authors.initials: C
authors.lastname: Datz
authors.forename: F
authors.initials: F
authors.lastname: Hackl
authors.forename: S
authors.initials: S
authors.lastname: Allinger
authors.forename: K
authors.initials: K
authors.lastname: Grünewald
authors.forename: J
authors.initials: J
authors.lastname: Patsch
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D002908:Chronic Disease; D004796:Clinical Enzyme Tests; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification; D006526:Hepatitis C / Q000175:diagnosis / Q000628:therapy* / Q000821:virology; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D000410:Alanine Transaminase