title: Roles of ITPA and IL28B genotypes in chronic hepatitis C patients treated with peginterferon plus ribavirin.
abstract: It has been reported that inosine triphosphatase (ITPA) gene variants protect against ribavirin-induced anemia in patients treated for chronic hepatitis C. IL28B variants also influence the treatment response of peginterferon plus ribavirin treatment in these patients. In the present study, we examined how ITPA and IL28B genotypes have clinical impacts on treatment-induced hematotoxicities and treatment response in HCV-infected patients treated with peginterferon plus ribavirin. ITPA genotypes (rs1127354 and rs6051702) and IL28B genotype (rs8099917) were determined by TaqMan SNP assay. We compared clinical background, treatment course and treatment response in terms of these genotypes. Only IL28B rs8099917 major type could predict sustained virological response. ITPA rs1127354 major type leads to significantly greater ribavirin-induced anemia than ITPA rs1127354 minor type between days 0 and 84. We noticed that IL28B rs8099917 minor genotype was associated with higher reduction of neutrophils and platelets. ITPA rs1127354 is useful for the prediction of ribavirin-induced anemia in the early phase after the commencement of peginterferon plus ribavirin treatment and IL28B rs8099917 is useful for the prediction of sustained virological response. Use of the combination of these two genotypes could lead to safe and effective treatment of chronic hepatitis C patients.
authors.affiliation: Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan. miyamura__ta@hotmail.com
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Miyamura
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kanda
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakamoto
authors.forename: Shuang
authors.initials: S
authors.lastname: Wu
authors.forename: Xia
authors.initials: X
authors.lastname: Jiang
authors.forename: Makoto
authors.initials: M
authors.lastname: Arai
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Fumio
authors.initials: F
authors.lastname: Imazeki
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; 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; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase; C100416:peginterferon alfa-2a