title: Evaluation of twice-daily administration of interferon-beta for chronic hepatitis C.
abstract: To improve the efficacy of interferon (IFN) in the treatment of chronic hepatitis C, administration of IFN-beta twice per day was evaluated. Thirty-eight patients with chronic hepatitis C (26 males and 12 females, aged 25-67 years) were included. Patients were treated with a new protocol that included twice-daily treatment with IFN-beta. Three million units (MU) of IFN-beta was administered twice daily every day for 4 weeks followed by 10 MU of IFN-alpha2b, every day for 2 weeks and then three times a week for 18 weeks (total IFN-beta, 148 MU; IFN-alpha2b, 680 MU). Complete responders (CR) were defined by alanine aminotransferase levels that normalized within 6 months after completion of IFN therapy and remained normal for more than 6 months, and by serum hepatitis C virus (HCV) RNA levels that became negative as determined using the Amplicor assay. Twenty-one of 38 (55.3%) patients were CR. Nine of 21 (42.9%) patients with HCV serotype 1 were responders compared with nine of 12 (75.0%) patients with HCV serotype 2. In patients with an HCV titre greater than 1 million equivalents ml-1 (1 MEq ml-1), nine of 24 (37.5%) responded, and in patients with HCV titres less than 1 MEq ml-1, 12 of 14 (85.7%) responded. In patients with HCV serotype 1 and greater than 1 MEq ml-1 HCV RNA, four of 15 (26.7%) responded to IFN. Two-thirds (66.7%) of the patients who became negative for HCV RNA after 2 weeks of therapy responded, while 72.7% of those with positive HCV RNA after 2 weeks of therapy were non-responders. Proteinuria was frequently observed as an adverse effect of twice-daily administration of IFN-beta. The combination of twice-daily administration of IFN-beta for 4 weeks followed by IFN-alpha showed a high response rate in patients with chronic hepatitis C, but in patients with both serotype 1 and a high titre of HCV RNA, response rates were still low. Thus, the HCV RNA titre 2 weeks after starting therapy with IFN was useful for predicting the eventual response to IFN.
authors.affiliation: The First Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kakizaki
authors.forename: H
authors.initials: H
authors.lastname: Takagi
authors.forename: T
authors.initials: T
authors.lastname: Yamada
authors.forename: T
authors.initials: T
authors.lastname: Ichikawa
authors.forename: T
authors.initials: T
authors.lastname: Abe
authors.forename: N
authors.initials: N
authors.lastname: Sohara
authors.forename: T
authors.initials: T
authors.lastname: Kosone
authors.forename: M
authors.initials: M
authors.lastname: Kaneko
authors.forename: J
authors.initials: J
authors.lastname: Takezawa
authors.forename: H
authors.initials: H
authors.lastname: Takayama
authors.forename: T
authors.initials: T
authors.lastname: Nagamine
authors.forename: M
authors.initials: M
authors.lastname: Mori
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005069:Evaluation Studies as Topic; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D016899:Interferon-beta / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D016899:Interferon-beta; D000410:Alanine Transaminase