title: A randomized controlled trial of high-dose maintenance interferon therapy in chronic hepatitis C.
abstract: In chronic hepatitis C virus (HCV) infection, the rate of sustained response to interferon is low. We evaluated, in patients responding to a 26-week course of interferon, the effect of high-dose maintenance therapy in preventing relapse. Three hundred and ten patients with chronic HCV infection (38.3% with cirrhosis, 80.6% with HCV type 1) received interferon alfa-2b for 26 weeks (10 MU tiw for 8 weeks, then 5 MU tiw for 18 weeks). One hundred and twenty-four subjects (40%) normalized aminotransferases, and were allocated randomly either to continue on 5 MU tiw for a further 26 weeks (prolonged therapy group: 60 patients) or to stop interferon (brief therapy group: 64 patients). Fifty-two weeks after stopping interferon the overall sustained biochemical response rate was 13.2% (41/310). The number of patients with normal aminotransferases was comparable between the prolonged and brief therapy groups (30% vs. 35.9%, P = n.s.), and the rate of HCV-RNA clearance was similar (48.8% vs. 42.4%, P = n.s.). The timing of posttreatment relapse was not influenced by the duration of therapy. Fifty-nine patients (19%) did not complete therapy due to adverse effects. Multivariate analysis identified four features predicting sustained biochemical response in subjects normalizing aminotransferases under therapy: negative HCV-RNA at end of therapy, normal aminotransferases at 4 weeks of therapy, high baseline aminotransferases, and high baseline platelets. Infection with HCV type 1 was not a significant predictor of response, due to its high prevalence in our population (80.6%). It is concluded that in patients with chronic hepatitis C mostly infected by HCV type 1, a prolonged high-dose interferon course (900 MU over 52 weeks) did not increase the rate of sustained biochemical response and of HCV-RNA clearance in comparison to a brief course (510 MU over 26 weeks).
authors.affiliation: Clinica Medica I, Palermo, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Di Marco
authors.forename: O
authors.initials: O
authors.lastname: Lo Iacono
authors.forename: C
authors.initials: C
authors.lastname: Cammà
authors.forename: P L
authors.initials: PL
authors.lastname: Almasio
authors.forename: A
authors.initials: A
authors.lastname: Vaccaro
authors.forename: P
authors.initials: P
authors.lastname: Fuschi
authors.forename: M
authors.initials: M
authors.lastname: Giunta
authors.forename: C
authors.initials: C
authors.lastname: Fabiano
authors.forename: L
authors.initials: L
authors.lastname: Pagliaro
authors.forename: A
authors.initials: A
authors.lastname: Craxì
mesh_terms: D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001706:Biopsy; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000821:virology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010976:Platelet Count; D012367:RNA, Viral / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins; D012008:Recurrence; D013997:Time Factors; D000637:Transaminases / Q000032:analysis / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D000637:Transaminases