| Hepatitis C virus(HCV) poses a serious global health problem due to its adverse clinical outcomes, such as cirrhosis and hepatocellular carcinoma. Treatment for chronic hepatitis C consists of interferon(IFN) plus ribavirin(RBV) and protease inhibitors such as telaprevir and boceprevir. The treatment response likely depends on a complex host-virus interaction. The influence of host gene polymorphisms has attracted attention in recent years. Therefore, establishing calculable pre-treatment predictors for response to IFN-α/RBV in the Chinese population should guide clinical decisions and improve costeffectiveness.Objectives: This study aims to determine the association between therapeutic response and IL28 B, IL28 RA, IL10 RB and Mx A polymorphisms in the Chinese Han population and provide scientic basis to personalized treatment of HCV infection.Methods: The study cohort consisted of 299 chronic hepatitis C patients treated with interferon(IFN)-α-2b and ribavirin. Biochemical indices were measured at baseline. Serum hepatitis C virus(HCV) RNA was detected at weeks 0, 4, 12, 24, 48 and 72 of therapy. The indicators of treatment response include rapid viral response(RVR), early viral response(EVR), and sustained viral response(SVR)。Six single nucleotide polymorphisms(rs12980275, rs10903035, rs11249006, rs2071430, rs17000900 and rs2834167) were genotyped using the ABI Taq Man allelic discrimination assay. After building of the database, we used SPSS 13.0 and STATA 10.0 software to analyze the association of the distribution of these genotypes with therapeutic response.Results: IL28 B rs12980275 was associated with treatment response in the Chinese Han population. Patients carrying G alle had a reduced sustained viral response compared with patients carrying the A alle(additive model: adjusted OR = 0.52, 95% CI: 0.32-0.86,P=0.01). In addition, the protective effect of genotype AA was independent of baseline viral load. Patients carrying Mx A rs17000900 CC genotype are more likely to achieve SVR(additive model: adjusted OR= 0.54,95% CI= 0.30-0.99,P=0.048). RVR, EVR, glucose and alpha fetoprotein might also help predict treatment response. The area under the receiveroperating characteristic curve was 0.802. It took less time for patients with the AA genotype to achieve a viral load < 500 copies/m L(P = 0.03). During the therapy, the tread of viral load reducing differ among different rs12980275 genotypes, especially in subgroup with a viral load > 106 copies/m L. RVR also influences relapse rate. Patients in SVR group and relapse group achieve significantly different RVR(77.78% vs 52.17%, P<0.05) and EVR(93.81% vs 82.35%, P<0.05). In the stepwise regression analysis, RVR, GLU and AFP are independent factors in predicting relapse.Conclusion: IL28 B rs12980275 AA genotype is a strong predictor of positive response to IFN therapy in Chinese Han patients with hepatitis C. RVR is an independent factor of SVR and relapse. |
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