title: Impact of IL28B and PNPLA3 polymorphisms on treatment outcomes in patients infected with genotype 6 hepatitis C virus.
abstract: OBJECTIVE
  Interleukin-28B (IL28B) and patatin-like phospholipase domain containing 3 (PNPLA3) gene polymorphisms are associated with hepatitis C virus (HCV) clearance and fatty liver, respectively. We aimed to test if their polymorphisms are associated with virologic responses in Chinese chronic hepatitis C (CHC) patients.
  
  
  METHODS
  This was a retrospective-prospective cohort study. Consecutive patients infected by genotype 1 and 6 HCV received antiviral therapy were included. Host IL-28B rs12979860/rs8099917 and PNPLA3 rs738409 genotype were tested. The primary outcome was sustained virologic response (sustained virologic response [SVR]: undetectable HCV RNA 24 weeks post-treatment).
  
  
  RESULTS
  From 305 patients had positive antibody to HCV, 52 and 31 patients infected by genotype 1 and 6 HCV, respectively were recruited. Mean age was 58 ± 11 years; 70% were male. Mean baseline HCV RNA was 6.8 ± 2.7 log IU/ml. The SVR for patients infected by genotype 1 and 6 HCV was 67.3% and 90.3%, respectively. The proportions of IL28B genotypes were 78%, 21%, and 1% for TT/TG/GG at rs8099917, and 81%, 18%, and 1% for CC/TC/TT at rs12979860, respectively. The proportions of PNPLA3 rs738409 genotypes were 16%, 36%, and 48% for GG/GC/CC. IL28B genotype was significantly associated with SVR in patients infected by genotype 1 but not genotype 6 HCV, with 80% versus 38% of patients infected by genotype 1 achieved SVR carried TT versus TG/GG at rs8099917, respectively (P=0.003). PNPLA3 genotype was not associated with SVR.
  
  
  CONCLUSIONS
  IL28B gene with rs8099917 T allele as an independent predictor of SVR in Chinese CHC patients infected by genotype 1 but not genotype 6 HCV.
authors: Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors: Grace Lai-Hung
authors: GL
authors: Wong
authors: Henry Lik-Yuen
authors: HL
authors: Chan
authors: Chi-Hang
authors: CH
authors: Tse
authors: Polly Oi-Ying
authors: PO
authors: Chan
authors: Joe Cho-Yiu
authors: JC
authors: Cheng
authors: Jackie Siu-Woon
authors: JS
authors: Cheng
authors: Sharon Hoi-Ying
authors: SH
authors: Lau
authors: Elbert Kam-Yeung
authors: EK
authors: Lee
authors: Justin Ming-Yin
authors: JM
authors: Ma
authors: Anthony Wing-Hung
authors: AW
authors: Chan
authors: Paul Cheung-Lung
authors: PC
authors: Choi
authors: Vincent Wai-Sun
authors: VW
authors: Wong
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000998:Antiviral Agents / Q000627:therapeutic use*; D044466:Asian People; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy / Q000235:genetics* / Q000821:virology*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008049:Lipase / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D012189:Retrospective Studies; D016896:Treatment Outcome; D000095022:Interferon Lambda; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; D008049:Lipase; D008565:Membrane Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
keywords: cirrhosis; early virologic response; liver biopsy; rapid virologic response; sustained virologic response; transient elastography