title: Dose increase augments response rate to interferon-alpha in chronic hepatitis C.
abstract: Approximately 50% of patients with chronic hepatitis C respond to treatment with interferon-alpha. The aim of this randomized controlled trial was to evaluate whether an increase in dose of interferon-alpha augments response rate. One hundred thirty-eight patients with newly diagnosed chronic hepatitis C received a three-month course of 3 MU IFN-alpha2b administered every two days. All patients were anti-HCV and HCV-RNA (PCR) positive. Prior to treatment, a liver biopsy was performed. Complete response was defined by normal serum ALT concentrations and disappearance of HCV-RNA. After three months, 60 nonresponders were randomized (stratified according to histology) either to continue 3 MU interferon-alpha2b every two days for another six months (group A, total dose: 410 MU) or to receive increasing doses of interferon-alpha2b (6 MU every two days for three months, followed by 10 MU every two days for three months) (group B, total dose: 870 MU). Serum ALT concentrations were measured monthly and HCV-RNA at three-month intervals. Liver biopsy was repeated six months after end of treatment. Pretreatment characteristics of the randomized patients were: group A: N = 30; male/female: 20/10; age: 54 +/- 10 years; CPH 9, CAH 8, cirrhosis 13; mean ALT 108 +/- 98 units/liter; group B: N = 30; male/female: 21/9; age: 57 +/- 15 years; CPH 10, CAH 9, cirrhosis 11; mean ALT 90 +/- 40 units/liter. At the end of treatment six patients in group B but none in group A became responders [P = 0.011 (Fisher's exact test), intent-to-treat analysis]. All six responders were noncirrhotics. High-dose interferon was not tolerated by six patients in group B. Noncompliance resulted in five dropouts in group A and one in group B. During the six-month follow-up, four of the six responders relapsed. A patient in group A with increased serum ALT concentration but negative HCV-RNA at the end of treatment became a full responder after six months. Of nonresponders to 3 MU interferon alpha2b every two days for three months, 20% responded to higher interferon doses, but none to continued standard dose. Prolonged treatment with interferon may be necessary to obtain a sustained response. However, treatment with higher-dose interferon was not tolerated in 20% of the patients.
authors.affiliation: Department of Internal Medicine IV, University of Vienna, Austria.
authors.forename: P
authors.initials: P
authors.lastname: Ferenci
authors.forename: R
authors.initials: R
authors.lastname: Stauber
authors.forename: A
authors.initials: A
authors.lastname: Propst
authors.forename: R
authors.initials: R
authors.lastname: Fiedler
authors.forename: C
authors.initials: C
authors.lastname: Müller
authors.forename: M
authors.initials: M
authors.lastname: Gschwantler
authors.forename: K
authors.initials: K
authors.lastname: Schütze
authors.forename: C
authors.initials: C
authors.lastname: Datz
authors.forename: G
authors.initials: G
authors.lastname: Judmaier
authors.forename: W
authors.initials: W
authors.lastname: Vogel
authors.forename: G J
authors.initials: GJ
authors.lastname: Krejs
authors.forename: A
authors.initials: A
authors.lastname: Gangl
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D001706:Biopsy; D002908:Chronic Disease; D004796:Clinical Enzyme Tests; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification; D006526:Hepatitis C / Q000175:diagnosis / Q000473:pathology / Q000628:therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins; D016896:Treatment Outcome
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D000410:Alanine Transaminase