title: Maintenance therapy with ribavirin in patients with chronic hepatitis C who fail to respond to combination therapy with interferon alfa and ribavirin.
abstract: To assess the efficacy and safety of maintenance therapy with ribavirin alone in chronic hepatitis C, 108 patients were treated with the combination of interferon alfa and ribavirin for 24 weeks; those who failed to have a virologic response were offered enrollment in a randomized, double-blind, controlled trial of ribavirin (1,000-1,200 mg daily) versus placebo for the subsequent 48 weeks. Patients were monitored at regular intervals with symptom questionnaires, serum aminotransferase levels, hepatitis C virus (HCV) RNA levels, and complete blood counts and underwent liver biopsy at the completion of therapy. Among 108 patients, 50 were still HCV RNA positive after 24 weeks of treatment, of whom 34 agreed to be randomized to continue either ribavirin monotherapy or placebo. Among 17 patients who received placebo, there was no overall improvement in symptoms, serum alanine aminotransferase (ALT) levels, HCV RNA levels, or hepatic histology. Among the 17 patients who received ribavirin, serum ALT levels and necroinflammatory features of liver histology were improved, whereas symptoms, HCV RNA levels, and hepatic fibrosis scores were not changed significantly from baseline. Responses to ribavirin seemed to be categorical, such that 8 patients (47%) had definite improvement in liver histology. Patients with improved histology had improvements in serum ALT levels both on combination therapy and after switching to ribavirin monotherapy. In conclusion, continuation of ribavirin monotherapy may maintain serum biochemical improvements that occur during interferon-ribavirin combination therapy in some patients and that these improvements are often associated with decreases in necroinflammatory changes in the liver. Whether these improvements will ultimately result in prevention of progression of hepatitis C requires further study.
authors.affiliation: Liver Diseases Section, Digestive Diseases Branch, and Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Hoofnalej@extra.niddk.nih.gov
authors.forename: Jay H
authors.initials: JH
authors.lastname: Hoofnagle
authors.forename: Marc G
authors.initials: MG
authors.lastname: Ghany
authors.forename: David E
authors.initials: DE
authors.lastname: Kleiner
authors.forename: Edward
authors.initials: E
authors.lastname: Doo
authors.forename: Theo
authors.initials: T
authors.lastname: Heller
authors.forename: Kittichai
authors.initials: K
authors.lastname: Promrat
authors.forename: Janus
authors.initials: J
authors.lastname: Ong
authors.forename: Farooq
authors.initials: F
authors.lastname: Khokhar
authors.forename: Alejandro
authors.initials: A
authors.lastname: Soza
authors.forename: David
authors.initials: D
authors.lastname: Herion
authors.forename: Yoon
authors.initials: Y
authors.lastname: Park
authors.forename: James E
authors.initials: JE
authors.lastname: Everhart
authors.forename: T Jake
authors.initials: TJ
authors.lastname: Liang
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001706:Biopsy; D004311:Double-Blind Method; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D012254:Ribavirin