Host interleukin-28B genetic variants versus viral kinetics in determining responses to standard-of-care for Asians with hepatitis C genotype 1

BackgroundBoth interleukin-28B genetic variants and on-treatment virological responses are factors predictive of treatment outcome in hepatitis C virus genotype 1 (HCV-1) patients. We aimed to compare the clinical significance of the two factors.MethodsRs8099917 genotype and on-treatment responses were determined in 182 HCV-1 patients with 48-week peginterferon/ribavirin.ResultsComparing to patients with rs8099917 TG/GG genotype, those with TT genotype had significantly higher rapid virological response (RVR, 46.2% vs. 19.2%, P = 0.01) and sustained virological response (SVR, 85.3% vs. 42.3%, P < 0.001) rates. Logistic regression analysis revealed that the strongest factor predictive of a RVR was the carriage of rs8099917 TT genotype (odds ratio/95% confidence intervals [OR/CI]: 4.25/1.39-13.01). The most important factor predictive of an SVR was the attainment of a RVR (OR/CI: 57.22/6.23-525.37), followed by the carriage of rs8099917 TT genotype (OR/CI: 10.06/3.12-32.44). However, while on-treatment factors were taken into account, the cEVR was the most important determinant to an SVR (OR/CI:54.98/9.07-333.38), whereas the influence of rs8099917 genotype became non-significant in non-RVR patients.ConclusionsRs8099917 TT genotype is significantly independently predictive of on-treatment virological responses, which were the major determinants of an SVR, in Asian HCV-1 patients.

► The IL-28B genetic variant is the most important predictor of attaining a RVR.
► RVR is the most important factor for an SVR irrespective of host IL-28B genotype.
► The effect of IL-28B gene was restricted to non-RVR/high viral loads patients.
► CEVR is the only determinant for non-RVR patients regardless IL-28B genes.
► Changes of viral kinetics overweight host IL-28 genetic variants for HCV-1.