title: Impact of ribavirin dosage in chronic hepatitis C patients treated with simeprevir, pegylated interferon plus ribavirin combination therapy.
abstract: The factors associated with sustained virologic response (SVR) in chronic hepatitis C (CH-C) genotype 1 patients treated with simeprevir (SMV), pegylated interferon (Peg-IFN) plus ribavirin (RBV) triple therapy have not been fully investigated. Two hundred and twenty-nine treatment-naïve CH-C patients treated with SMV triple therapy were enrolled in this study. The overall SVR rate was 87% in per-protocol analysis. In multivariate analysis, the interleukin (IL) 28B genotype (rs8099917, TT vs. non-TT, odds ratio [OR]: 0.044, P = 0.001) and RBV dose (< 10/10-12/ ≥ 12 mg/kg/day, OR: 4.513, P = 0.041) were significant factors associated with SVR. In patients with the IL28B non-TT genotype, RBV dose affected SVR dose-dependently in stratified analysis of RBV dose (P = 0.015); it was 44% (8/18) for patients administered <10 mg/kg/day of RBV, 78% (14/18) for those administered 10-12 mg/kg/day of RBV, and 100% (3/3) for those administered ≥12 mg/kg/day of RBV, whereas in patients with the IL28B TT genotype, a significant correlation between SVR and RBV dose was not observed (P = 0.229). Regarding RBV dose reduction of less than 10 mg/kg/day, the inosine triphosphate pyrophosphatase (ITPA) genotype (rs1127354, CC vs. non-CC, OR: 0.239, P = 0.003) and age (by 1 y.o., OR: 1.084, P = 0.002) were significant independent factors. RBV dosage affected SVR dose-dependently in patients with the IL28B non-TT genotype treated with SMV triple therapy. Special attention to anemia progression and RBV dosage should be paid to aged patients with the ITPA CC genotype. J. Med. Virol. 88:1776-1784, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Tahata
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hiramatsu
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Tsugiko
authors.initials: T
authors.lastname: Oze
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Urabe
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Morishita
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Yamada
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yakushijin
authors.affiliation: Osaka Rosai Hospital, Sakai, Osaka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hosui
authors.affiliation: Osaka Police Hospital, Osaka, Osaka, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Oshita
authors.affiliation: NTT West Osaka Hospital, Osaka, Osaka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kaneko
authors.affiliation: Kansai Rousai Hospital, Amagasaki, Hyogo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hagiwara
authors.affiliation: National Hospital Organization, Osaka National Hospital, Osaka, Osaka, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Mita
authors.affiliation: Japan Community Health Care Organization Osaka Hospital, Osaka, Osaka, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ito
authors.affiliation: Kaizuka City Hospital, Kaizuka, Osaka, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Toyonaka Municipal Hospital, Toyonaka, Osaka, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Inada
authors.affiliation: Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Osaka, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Katayama
authors.affiliation: Minoh City Hospital, Minoh, Osaka, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Tamura
authors.affiliation: Ikeda Municipal Hospital, Ikeda, Osaka, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Imai
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Hikita
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Sakamori
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tatsumi
authors.affiliation: Kansai Rousai Hospital, Amagasaki, Hyogo, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Hayashi
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000069616:Simeprevir / Q000008:administration & dosage* / Q000627:therapeutic use; D000072230:Sustained Virologic Response; D016896:Treatment Outcome; D000095022:Interferon Lambda; D000097630:Inosine Triphosphatase
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011755:Pyrophosphatases; D011994:Recombinant Proteins; D012254:Ribavirin; D000069616:Simeprevir; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase; C100416:peginterferon alfa-2a
keywords: chronic hepatitis C; interleukin 28B; ribavirin dose; simeprevir; sustained virologic response