title: An open-label randomized controlled study of pegylated interferon/ribavirin combination therapy for chronic hepatitis C with versus without fluvastatin.
abstract: Pegylated interferon (PEG-IFN)/ribavirin combination therapy is the standard-of-care (SOC) treatment for chronic hepatitis C patients infected with hepatitis C virus (HCV) genotype 1b and high viral load. The addition of fluvastatin to SOC treatment has been suggested to be effective for better outcome in retrospective pilot analyses. We investigated whether the combination of fluvastatin with PEG-IFN/ribavirin could actually improve sustained viral response (SVR) in patients with HCV genotype 1b and high viral load. A randomized, open-labeled, controlled study was conducted between July 2008 and December 2009 in 101 chronic hepatitis C patients allocated to PEG-IFN/ribavirin combination therapy with or without fluvastatin. SVR rates were calculated in groups, stratifying host and viral factors. We also analyzed predictive factors for SVR among patients on fluvastatin with multivariate regression analysis. Rapid and early virological, and end of treatment response rates in the fluvastatin group were not significantly different from those in the non-fluvastatin group. Notwithstanding, SVR rate was significantly higher in the fluvastatin group than in the non-fluvastatin group (63.0%vs 41.7%, P = 0.0422). Comparison of the two groups stratifying demographic data and HCV characteristics showed significantly higher SVR rates to more than 80% in males, more than two mutations in the interferon sensitivity determining region (ISDR), and a history of relapse among the fluvastatin group than the non-fluvastatin group. Being male and major genotype IL28B single nucleotide polymorphisms (SNPs) were independent predictive factors for SVR among patients on fluvastatin with multivariate analysis. Fluvastatin-combined with PEG-IFN/ribavirin therapy significantly improves SVR rates in patients with HCV genotype 1b and high viral load. Male and major genotype IL28B SNPs were independent predictors for SVR among patients on fluvastatin combination therapy.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Kondo
authors.forename: M
authors.initials: M
authors.lastname: Atsukawa
authors.forename: A
authors.initials: A
authors.lastname: Tsubota
authors.forename: N
authors.initials: N
authors.lastname: Itokawa
authors.forename: T
authors.initials: T
authors.lastname: Fukuda
authors.forename: Y
authors.initials: Y
authors.lastname: Matsushita
authors.forename: H
authors.initials: H
authors.lastname: Kidokoro
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Narahara
authors.forename: K
authors.initials: K
authors.lastname: Nakatsuka
authors.forename: H
authors.initials: H
authors.lastname: Kanazawa
authors.forename: C
authors.initials: C
authors.lastname: Sakamoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000008:administration & dosage; D000998:Antiviral Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination / Q000379:methods; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage*; D005260:Female; D000077340:Fluvastatin; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D007372:Interferons / Q000008:administration & dosage*; D007378:Interleukins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000008:administration & dosage*; D012737:Sex Factors; D016896:Treatment Outcome; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D000924:Anticholesteremic Agents; D000998:Antiviral Agents; D005229:Fatty Acids, Monounsaturated; D000077340:Fluvastatin; D007211:Indoles; D007372:Interferons; D007378:Interleukins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda