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        IL28B Is Associated with Outcomes of Chronic HBV Infection

        Xiaodong Shi,Junqi Niu,Xiumei Chi,Yu Pan,Yanhang Gao,Wanyu Li,Chen Yang,Jin Zhong,Damo Xu,Manna Zhang,Gerald Minuk,Jing Jiang 연세대학교의과대학 2015 Yonsei medical journal Vol.56 No.3

        Purpose: The role of IL28B gene variants and expression in hepatitis B virus (HBV) infections are not well understood. Here, we evaluated whether IL28B gene expression and rs12979860 variations are associated with HBV outcomes. Materialsand Methods: IL28B genetic variations (rs12979860) were genotyped by pyrosequencingof DNA samples from 137 individuals with chronic HBV infection [50 inactive carriers (IC), 34 chronic hepatitis B (CHB), 27 cirrhosis, 26 hepatocellular carcinoma (HCC)], and 19 healthy controls. IL28A/B mRNA expression in peripheralblood mononuclear cells was determined by qRT-PCR, and serum IL28B proteinwas measured by ELISA. Results: Patients with IL28B C/C genotype had greater IL28A/B mRNA expression and higher IL28B protein levels than C/T patients. Within the various disease stages, compared to IC and healthy controls, IL28B expression was reduced in the CHB, cirrhosis, and HCC cohorts (CHB vs. IC, p=0.02; cirrhosis vs. IC, p=0.01; HCC vs. IC, p=0.001; CHB vs. controls, p<0.01; cirrhosis vs. controls, p<0.01; HCC vs. controls, p<0.01). When stratified with respect to serum HBV markers in the IC and CHB cohorts, IL28B mRNA and protein levels were higher in HBeAg-positive than negative individuals (p=0.01). Logistic regression analysis revealed that factors associated with high IL28B proteinlevels were C/C versus C/T genotype [p=0.016, odds ratio (OR)=0.25, 95% confidence interval (CI)=0.08‒0.78], high alanine aminotransferase values (p<0.001, OR=8.02, 95% CI=2.64‒24.4), and the IC stage of HBV infection (p<0.001). Conclusion: Our data suggest that IL28B genetic variations may play an important role in long-term development of disease in chronic HBV infections.

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