title: Role of IL28B and inosine triphosphatase polymorphisms in the treatment of chronic hepatitis C virus genotype 6 infection.
abstract: IL28B and inosine triphosphatase (ITPA) polymorphisms are able to predict treatment response and degree of ribavirin-related anaemia, respectively, in the treatment of chronic hepatitis C virus (HCV) infection. However, their roles in the treatment of chronic HCV genotype 6 remain undetermined. Sixty patients who were infected with HCV genotype 6 were commenced on 48 weeks of combination pegylated interferon and ribavirin therapy. Response to therapy, profiles of haemoglobin changes and platelet counts during therapy and their associations with IL28B rs8099917 and ITPA rs1127354 polymorphisms were analysed. The overall sustained virologic response (SVR) rate was 91.7%. 18 patients (30.0%) required a reduction in ribavirin dosage. The distribution of IL28B rs8099917 TT/TG genotypes and ITPA rs1127354 CC/CA genotypes were in Hardy-Weinberg equilibrium. IL28B rs8099917 TT genotype, when compared to TG genotype, was significantly associated with an increased SVR rate (96.2% and 62.5%, respectively) and was the only clinical parameter that predicted SVR (P = 0.014). The same significant association was observed when analysing allelic frequencies (T vs G, P = 0.001). ITPA rs1127354 CA genotype, when compared to CC genotype, was associated with lesser degree of anaemia throughout therapy (P < 0.05 for all time points). ITPA polymorphisms showed no association with changes in platelet count throughout therapy (P > 0.05 for all time points) and was not associated with SVR (P = 0.640). In chronic HCV genotype 6 infection, IL28B polymorphisms were associated with response to therapy. ITPA polymorphisms influenced the degree of anaemia but not thrombocytopenia during therapy.
authors.affiliation: Department of Medicine, the University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.
authors.forename: W-K
authors.initials: WK
authors.lastname: Seto
authors.forename: O T-Y
authors.initials: OT
authors.lastname: Tsang
authors.forename: K
authors.initials: K
authors.lastname: Liu
authors.forename: J M-C
authors.initials: JM
authors.lastname: Chan
authors.forename: D K-H
authors.initials: DK
authors.lastname: Wong
authors.forename: J
authors.initials: J
authors.lastname: Fung
authors.forename: C-L
authors.initials: CL
authors.lastname: Lai
authors.forename: M-F
authors.initials: MF
authors.lastname: Yuen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006454:Hemoglobins / Q000032:analysis; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics*; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult; D000097630:Inosine Triphosphatase; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D006454:Hemoglobins; D007372:Interferons; D007378:Interleukins; D011755:Pyrophosphatases; D012254:Ribavirin; D000097630:Inosine Triphosphatase; C000624353:interferon-lambda, human; D000095022:Interferon Lambda