Clinical utility of host genetic IL-28B variants in hepatitis C virus genotype 1 Asian patients retreated with pegylated interferon plus ribavirin

Chung-Feng Huang, Ming-Lun Yeh, Meng-Hsuan Hsieh, Ming-Yen Hsieh, Zu-Yau Lin, Shinn-Cherng Chen, Liang-Yen Wang, Jee-Fu Huang, Suh-Hang Hank Juo, Yi-Ching Lin, Chia-Yen Dai, Wan-Long Chuang, Ming-Lung Yu
Journal of Gastroenterology and Hepatology 2013, 28 (9): 1515-20

BACKGROUND AND AIM: 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.

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