title: Genetic variation in interleukin 28B and response to antiviral therapy in patients with dual chronic infection with hepatitis B and C viruses.
abstract: Concurrent infection with hepatitis C virus (HCV) and hepatitis B virus (HBV) was not uncommon in China. To date, information on predictors of response to treatment of dually-infected HCV/HBV is limited. The aim of this study was to evaluated whether determination of the interleukin 28B (IL-28B) polymorphism statuses sufficient to predict treatment response of interferon (IFN)-based therapy in patients chronically infected with both hepatitis B and C viruses. We investigated the role of IL28B variations (rs8099917 and rs12979860) in response to IFN-based treatment and evaluated its association with the risk of the null virological response (NVR) in HCV /HBV dually-infected patients. We found that the overall distributions of the genotypes among the sustained virological response (SVR), NVR groups were significantly different (P<0.001): patients with the rs8099917 TG genotype had an increased risk of NVR (odds ratio [OR] =2.37 95% confidence interval [CI] =1.16-4.83, P =0.017), and those with the GG genotype had a further increased risk of NVR (OR=4.23, 95% CI =1.17-15.3, P=0.027). The rs12979860 allele was also highly associated with treatment failure (CT/TT vs. CC; OR =2.04, 95%CI =1.05-3.97, P =0.037). Moreover, we found that IL28B rs8099917 G variants (TG+GG) interact with HCV genotype 1(G1) to result in higher risk of NVR (P=0.009), and that they are also associated with HBV DNA reactivation (TG+GG vs. TT, P=0.005). Furthermore, multivariate regression analysis show that the rs8099917 G allele was the most important factor significantly associated with a NVR in HCV G1 patients. This study suggest that IL28B genotyping may be a valid pretreatment predictor of which patients are likely to respond to treatment in this group of difficult-to-treat HCV/HBV dually-infected patients.
authors.affiliation: Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China ; Institute of Hepatology, Shenzhen Third people's Hospital, Shenzhen, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Guo
authors.forename: Guilin
authors.initials: G
authors.lastname: Yang
authors.forename: Jin
authors.initials: J
authors.lastname: Yuan
authors.forename: Peng
authors.initials: P
authors.lastname: Ruan
authors.forename: Mingxia
authors.initials: M
authors.lastname: Zhang
authors.forename: Xincun
authors.initials: X
authors.lastname: Chen
authors.forename: Boping
authors.initials: B
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006509:Hepatitis B / Q000188:drug therapy* / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda