title: A randomized trial to assess the efficacy of interferon alpha in combination with ribavirin in the treatment of interferon alpha nonresponders with chronic hepatitis C: superior efficacy of high daily dosage of interferon alpha in genotype 1.
abstract: A randomized trial was conducted to assess the efficacy of daily (QD) or thrice weekly (TIW) administration of interferon-alpha (IFN) in high doses in combination with ribavirin (1.0-1.2 g/day) in patients with chronic hepatitis C (CHC) who were nonresponders to previous IFN monotherapy. Interferon was administered as 10 MU IFN (QD or TIW) for 4 weeks, followed by 5 MU IFN (QD or TIW) for 20 weeks, and then by 3 MU IFN (QD or TIW) for 24 weeks. Sustained virological response (SVR) was evaluated in 142 patients who received at least one dose of medication. One-fourth of the patients achieved SVR, 26% of those treated with IFN QD and 25% of those treated with IFN TIW (P = 0.85). For genotype 1 patients, SVR rates were 32.4 and 15.8% for IFN QD and IFN TIW, respectively, whereas for genotype non-1 patients the corresponding SVR rates were 20.6 and 36.4%, respectively (test of homogeneity: P = 0.031). This finding was further confirmed by multivariate logistic regression analysis where a statistically significant interaction (P = 0.012) was found between treatment and HCV genotype indicating that the IFN QD regimen was superior to IFN TIW among genotype 1 patients whereas, among genotype non-1 patients, the two treatments were similar (odds ratio of SVR in IFN QD vs IFN TIW: 3.33 among genotype 1 patients, 95% CI: 1.00-11.14). In conclusion, re-treatment of patients not responding to previous IFN monotherapy with a combination of high daily dose of IFN with ribavirin may be beneficial for genotype 1 infected patients.
authors.affiliation: Western Attica General Hospital, Athens, Greece.
authors.forename: N C
authors.initials: NC
authors.lastname: Tassopoulos
authors.forename: D
authors.initials: D
authors.lastname: Tsantoulas
authors.forename: M
authors.initials: M
authors.lastname: Raptopoulou
authors.forename: T
authors.initials: T
authors.lastname: Vassiliadis
authors.forename: S
authors.initials: S
authors.lastname: Kanatakis
authors.forename: E
authors.initials: E
authors.lastname: Paraskevas
authors.forename: I
authors.initials: I
authors.lastname: Vafiadis
authors.forename: A
authors.initials: A
authors.lastname: Avgerinos
authors.forename: C
authors.initials: C
authors.lastname: Tzathas
authors.forename: S
authors.initials: S
authors.lastname: Manolakopoulos
authors.forename: I
authors.initials: I
authors.lastname: Ketikoglou
authors.forename: P
authors.initials: P
authors.lastname: Aggelis
authors.forename: K
authors.initials: K
authors.lastname: Goritsas
authors.forename: G
authors.initials: G
authors.lastname: Giannoulis
authors.forename: G
authors.initials: G
authors.lastname: Hatzis G
authors.forename: K
authors.initials: K
authors.lastname: Thomopoulos
authors.forename: E
authors.initials: E
authors.lastname: Akriviadis
authors.forename: V
authors.initials: V
authors.lastname: Sypsa
authors.forename: A
authors.initials: A
authors.lastname: Hatzakis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin