Human innate immune plays an essential role in the spontaneous clearance of acute infection and therapy of HCV. We investigated whether the SNPs in retinoic acid-inducible gene I-like receptor family were associated with HCV spontaneous clearance and response to treatment. To evaluate the clinical value of DDX58 rs3824456, rs10813831 and rs10738889 genotypes on HCV spontaneous clearance and treatment response in Chinese Han population, we genotyped 1001 HCV persistent infectors, 599 participants with HCV natural clearance and 354 patients with PEGylated interferon-α and ribavirin (PEG IFN-α/RBV) treatment. People carrying rs10813831-G allele genotype were more liable to achieve spontaneous clearance than the carriage of the T allele (dominant model: adjusted OR 1.35, 95% CI 1.08–1.71, P = 0.008). In rs10738889, the rate of persistent infection was significantly lower in patients with the TC genotype compared to those with TT genotype (dominant model: adjusted OR 1.36, 95% CI 1.06–1.74, P = 0.015). Multivariate stepwise analysis indicated that rs10738889, age, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were independent predictors for HCV spontaneous clearance. However, there were no significant differences in the three selection SNPs between the non-SVR group and the SVR group. These results suggest the DDX58 rs10813831 and rs10738889 are associated with spontaneous clearance of HCV, which may be identified as a predictive marker in the Chinese Han population of HCV.

The high rate of chronic hepatitis C (CHC) was one of the key issues of global public health concern. Interferon (IFN)-λ relevant genes were in the antiviral treatment pathway, not only influenced hepatitis C virus (HCV) spontaneous clearance, but also affected the IFN-mediated viral clearance. The aim of this study was to identify the association of interleukin 28B (IL28B), myxovirus resistance A (MxA) gene polymorphisms with HCV spontaneous clearance and therapeutic response in Chinese CHC patients. IL28B and MxA gene genotypes were detected among 231 CHC carriers, 428 subjects with HCV spontaneous clearance and 662 CHC patients with pegylated IFN-α and ribavirin (pegIFN-α/RBV) treatment. Patients with MxA rs2071430 TT genotype were more likely to develop HCV infection chronicity (additive model: odds ratio (OR) 1.22, 95% confidence interval (CI) 1.01–1.48, P = 0.042). IL28B rs1298075 variant genotypes (additive model: OR 0.58, 95% CI 0.34–0.98, P = 0.040) and MxA rs17000900 variant genotypes (additive model: OR 0.54, 95% CI 0.30–0.99, P = 0.048) were less likely to achieve a sustained virological response. The life table indicated that patients with IL28B rs1298075 AG genotype were slower to achieve a viral load <500 copies/ml (P = 0.018). During the treatment, the downward trend in viral load was different among each IL28B rs1298075 genotype, especially in subgroup with a baseline HCV-RNA >106 copies/ml (all P < 0.05). This study illustrated that the carriage of IL28B rs12980275 AA had a positive effect on treatment response to pegIFN-α/RBV among Chinese CHC patients.