Impact of IL28B and PNPLA3 polymorphisms on treatment outcomes in patients infected with genotype 6 hepatitis C virus

Grace Lai-Hung Wong, Henry Lik-Yuen Chan, Chi-Hang Tse, Polly Oi-Ying Chan, Joe Cho-Yiu Cheng, Jackie Siu-Woon Cheng, Sharon Hoi-Ying Lau, Elbert Kam-Yeung Lee, Justin Ming-Yin Ma, Anthony Wing-Hung Chan, Paul Cheung-Lung Choi, Vincent Wai-Sun Wong
Journal of Gastroenterology and Hepatology 2015, 30 (6): 1040-8

BACKGROUND/AIMS: 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.

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