title: Prediction of response to peginterferon-alfa-2b plus ribavirin therapy in Japanese patients infected with hepatitis C virus genotype 1b.
abstract: Variation at the IL-28B locus was recently reported to be a significant predictive factor of viral response to pegylated-interferon plus ribavirin combination therapy against chronic hepatitis C. Predictive factors for the effect of therapy, including IL-28B polymorphism rs8099917 and viral and clinical factors were investigated. A total of 288 patients were enrolled who were chronically infected with hepatitis C virus (HCV) genotype 1b and treated with combination therapy. Among them, 87 patients completed 48 weeks of therapy without dose reduction or discontinuation. In multivariate regression analysis, the rs8099917 TT genotype was the only independent factor significantly associated with sustained viral response (P = 0.016, OR 61.5), whereas substitutions at amino acid 70 (aa 70) of the HCV core protein (P = 0.038, OR 5.9) and non-TT genotypes (P = 0.002, OR 17.2) were associated with nonvirological response. Both factors were also associated with viral dynamics during the initial stage of the therapy. Correlation analysis revealed that rs8099917 genotype was correlated with γ-glutamyl transpeptidase, hyaluronic acid, and HCV core aa 70. In conclusion, host (IL-28B polymorphism) and viral (aa 70) factors independently affect response to combination therapy.
authors.affiliation: Division of Frontier Medical Science, Department of Medical and Molecular Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ochi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Abe
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Hayashida
authors.forename: Masataka
authors.initials: M
authors.lastname: Tsuge
authors.forename: Fukiko
authors.initials: F
authors.lastname: Mitsui
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Hiraga
authors.forename: Michio
authors.initials: M
authors.lastname: Imamura
authors.forename: Shoichi
authors.initials: S
authors.lastname: Takahashi
authors.forename: C
authors.initials: C
authors.lastname: Nelson Hayes
authors.forename: Waka
authors.initials: W
authors.lastname: Ohishi
authors.forename: Michaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution / Q000235:genetics; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D012254:Ribavirin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014758:Viral Core Proteins / Q000235:genetics; D019562:Viral Load / Q000187:drug effects; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; D014758:Viral Core Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C069130:nucleocapsid protein, Hepatitis C virus; C417083:peginterferon alfa-2b