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Background & aimsAlthough non-alcoholic fatty liver disease (NAFLD) has been studied extensively, the potential risk factors for NAFLD among chronic hepatitis B (CHB) patients have not been fully known.MethodsA population-based cohort of adult CHB patients without a history of alcohol drinking or NAFLD were recruited and followed up from October 2012 to January 2015 in Jiangsu province, China. Using Cox proportional hazards regression model, potential risk factors including viral and metabolic factors for NAFLD were evaluated.ResultsTwo thousand three hundred and ninety-three adult CHB patients (mean age 50.7 ± 13.2 years) were included in the cohort. With 4429 person-years of follow-up, 283 individuals progressed to NAFLD with an incidence rate of 63.89/1000 person-years. Overweight and obese CHB patients had an increased risk of NAFLD (overweight adjusted hazard ratio [HR], 3.10; 95% CI, 2.29-4.18; obese HR, 8.52; 95%CI, 5.93-12.25) compared to normal weight carriers. The incidence of NAFLD was associated with concurrent type 2 diabetes mellitus (DM) (HR, 1.88; 95%CI, 1.15-3.08). However, no associations between viral factors with NAFLD incidence rate were identified. In a subgroup of participants with concurrent type 2 DM, detectable HBV DNA levels were negatively associated with the development of NAFLD (HR, 0.37; 95%CI, 0.14-0.98). There was super-multiplicative interaction between BMI and gender with respect to incidence of NAFLD, with an ROR of 2.08 (95%CI, 1.02-4.23).ConclusionMetabolic factors play an important role in the presence of NAFLD among Chinese CHB patients. However, viral replication factors are not related to NAFLD except among those with concurrent type 2 DM.

Previously we identified that HBV(Hepatitis B virus) sequence variation, which may interact with host human leukocyte antigen ( HLA) genetic variation, could influence host risk of hepatocellular carcinoma ( HCC). More HBV-host interactions need to be identified. Protein tyrosine phosphatase nonreceptor type 12 ( PTPN12), serves as an antagonist to tyrosine kinase signaling, may play integral roles in immune response against HBV infection and the development of HCC. Rs11485985 was an expression quantitative trait loci ( eQTL) for PTPN12 by bioinformatics analyses. In this study, we genotyped the PTPN12 eQTL and sequenced the HBV region Enh II/ BCP/ PC in a case-control cohort including 1507 HBV-related HCC cases and 1560 HBV persistent carriers as controls. The variant genotype GG of rs11489585 increased HCC risk compared to the HBV persistent carriers (adjusted OR = 2.03, 95% confidence interval [ CIs] = 1.30-3.18). We also detected borderline significant associations of PTPN12 eQTL rs11489585 with HBV mutations ( P = 0.05 for G1799C). Taken together, PTPN12 may influence HCC risk accompanied by HBV mutations. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infection is a challenging global health problem. To identify genetic loci involved in chronic HBV infection, we designed a three-phase genome-wide association study in Han Chinese populations. The discovery phase included 951 HBV carriers (cases) and 937 individuals who had naturally cleared HBV infection (controls) and was followed by independent replications with a total of 2,248 cases and 3,051 controls and additional replications with 1,982 HBV carriers and 2,622 controls from the general population. We identified two new loci associated with chronic HBV infection: rs3130542 at 6p21.33 (near HLA-C, odds ratio (OR) = 1.33, P = 9.49 × 10−14) and rs4821116 at 22q11.21 (in UBE2L3, OR = 0.82, P = 1.71 × 10−12). Additionally, we replicated the previously identified associations of HLA-DP and HLA-DQ variants at 6p21.32 with chronic HBV infection. These findings highlight the importance of HLA-C and UBE2L3 in the clearance of HBV infection in addition to HLA-DP and HLA-DQ. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) have recently identified KIF1B as susceptibility locus for hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC). To further identify novel susceptibility loci associated with HBV–related HCC and replicate the previously reported association, we performed a large three-stage GWAS in the Han Chinese population. 523,663 autosomal SNPs in 1,538 HBV–positive HCC patients and 1,465 chronic HBV carriers were genotyped for the discovery stage. Top candidate SNPs were genotyped in the initial validation samples of 2,112 HBV–positive HCC cases and 2,208 HBV carriers and then in the second validation samples of 1,021 cases and 1,491 HBV carriers. We discovered two novel associations at rs9272105 (HLA-DQA1/DRB1) on 6p21.32 (OR = 1.30, P = 1.13×\(10^{−19}\)) and rs455804 (GRIK1) on 21q21.3 (OR = 0.84, P = 1.86×\(10^{−8}\)), which were further replicated in the fourth independent sample of 1,298 cases and 1,026 controls (rs9272105: OR = 1.25, P = 1.71×\(10^{−4}\); rs455804: OR = 0.84, P = 6.92×\(10^{−3}\)). We also revealed the associations of HLA-DRB1*0405 and 0901*0602, which could partially account for the association at rs9272105. The association at rs455804 implicates GRIK1 as a novel susceptibility gene for HBV–related HCC, suggesting the involvement of glutamate signaling in the development of HBV–related HCC.