title: Clinical utility of host genetic IL-28B variants in hepatitis C virus genotype 1 Asian patients retreated with pegylated interferon plus ribavirin.
abstract: OBJECTIVE
  Host interleukin-28B (IL-28B) genetic variants determine a sustained virological response (SVR) in hepatitis C virus genotype 1 (HCV-1) treatment-naïve patients. Its impact on treatment-experienced Asian patients with peginterferon/ribavirin in is to be elucidated.
  
  
  METHODS
  IL-28B rs8099917 genotype was determined in 70 HCV-1 treatment-experienced patients retreated with 48-week peginterferon/ribavirin.
  
  
  RESULTS
  The SVR rate was 60.0% and was significantly higher in previous relapsers than in nonresponders (72.7% and 13.3%, P < 0.001). Multivariate analysis revealed that the most important factor predictive of an SVR was previous relapse (Odds ratio [OR]/95% confidence interval [CI]: 14.76/2.72-80.06, P = 0.002), followed by the carriage of rs8099917 TT genotype (OR/95% C.I.: 7.67/1.27-46.49, P = 0.03). Comparing to patients with TG/GG genotype, those with TT genotype had significantly higher rates of rapid virological response (29.3% vs 0%, P = 0.03), end-of-treatment virological response (86.2% vs 50.0%, P = 0.01), SVR (69.0% vs 16.7%, P = 0.002), and lower relapse rate (22.0 % vs 66.7%, P = 0.04). The SVR rate was similarly low between previous nonresponders with different rs8099917 genotypes (12.5% vs 14.3%, P = 1). On the contrary, previous relapsers with rs8099917 TT genotype had a significantly higher SVR rate than those who carried rs8099917 TG/GG genotype (78.0 % vs 20.0%, P = 0.02). Stepwise logistic regression analysis revealed that the only factor predictive of an SVR in previous relapsers was the carriage of rs809997 TT genotype (OR/95% CI:18.50/1.82-188.39, P = 0.014).
  
  
  CONCLUSIONS
  Host IL-28B genetic variants played a role in Asian relapsers but not nonresponders retreated with peginterferon/ribavirin. Direct antiviral agents might be possibly avoidable in Asian relapsers with favorable IL-28B genotype.
authors.affiliation: Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chung-Feng
authors.initials: CF
authors.lastname: Huang
authors.forename: Ming-Lun
authors.initials: ML
authors.lastname: Yeh
authors.forename: Meng-Hsuan
authors.initials: MH
authors.lastname: Hsieh
authors.forename: Ming-Yen
authors.initials: MY
authors.lastname: Hsieh
authors.forename: Zu-Yau
authors.initials: ZY
authors.lastname: Lin
authors.forename: Shinn-Cherng
authors.initials: SC
authors.lastname: Chen
authors.forename: Liang-Yen
authors.initials: LY
authors.lastname: Wang
authors.forename: Jee-Fu
authors.initials: JF
authors.lastname: Huang
authors.forename: Suh-Hang Hank
authors.initials: SH
authors.lastname: Juo
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Lin
authors.forename: Chia-Yen
authors.initials: CY
authors.lastname: Dai
authors.forename: Wan-Long
authors.initials: WL
authors.lastname: Chuang
authors.forename: Ming-Lung
authors.initials: ML
authors.lastname: Yu
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011379:Prognosis; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D019233:Retreatment / Q000379:methods; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a
keywords: HCV-1; IL 28B; re-treatment