title: Human leukocyte antigen alleles and the response to pegylated interferon/ribavirin therapy in chronic hepatitis C patients.
abstract: Human leukocyte antigens (HLAs) may play a role in the clinical evolution of hepatitis C virus (HCV) infection. The present study was aimed at elucidating the association between the HLA loci and responses to combination therapy with pegylated interferon-alpha 2a (PEG-IFN) and ribavirin in Taiwanese. We enrolled a total of 208 treatment-naïve Taiwanese chronic hepatitis C (CHC) patients treated with combination therapy. Patients with sustained virological response (SVR) had a significantly higher frequency of genotype non-1b infection, lower pretreatment HCV RNA levels and a higher frequency of mild hepatic fibrosis (fibrosis score: F: 0-2). The HLA A24 and B40 alleles were significantly associated with SVR after adjusted for the other three confounding factors including HCV genotype, hepatic fibrosis and pretreatment serum HCV RNA levels. Haplotypes (B40-DRB1*3, B46- DRB1*9, Cw1- DQB1*3, and Cw1- DRB1*9) were significantly associated with SVR to combination therapy. For 167 patients with genotype 1b infection and viral load < or =5.6 logIU/ml or genotype non-1b infection, the B46 was significantly associated with sustained response with OR (odds ratio) [95% CI (confidence interval) of 0.047 (0.168-0.988)]. Haplotypes B40-DRB1*3, B46- DRB1*9, Cw1- DQB1*3, Cw1- DRB1*9 and DQB1*3- DRB1*9 were found to be associated with SVR to PEG-IFN/ribavirin therapy with OR (95% CI) of 0.179 (0.032-0.989), 0.313 (0.107-0.918), 0.350 (0.145-0.845), 0.282 (0.105-0.759) and 0.412 (0.174-0.978), respectively. We concluded that the virological and the host immunogenetic factors may possibly predict the response to combination therapy in CHC patients.
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Chia-Yen
authors.initials: CY
authors.lastname: Dai
authors.forename: Wan-Long
authors.initials: WL
authors.lastname: Chuang
authors.forename: Ming-Yen
authors.initials: MY
authors.lastname: Hsieh
authors.forename: Jee-Fu
authors.initials: JF
authors.lastname: Huang
authors.forename: Ya-Yun
authors.initials: YY
authors.lastname: Lin
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Chu
authors.forename: Nai-Jen
authors.initials: NJ
authors.lastname: Hou
authors.forename: Zu-Yau
authors.initials: ZY
authors.lastname: Lin
authors.forename: Shinn-Cherng
authors.initials: SC
authors.lastname: Chen
authors.forename: Ming-Yuh
authors.initials: MY
authors.lastname: Hsieh
authors.forename: Liang-Yen
authors.initials: LY
authors.lastname: Wang
authors.forename: Ming-Lung
authors.initials: ML
authors.lastname: Yu
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D005787:Gene Frequency; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013624:Taiwan; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D006680:HLA Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a