Search

Background & aims: Although 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. Methods: A 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. Results: Two 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). Conclusion: Metabolic 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. [ABSTRACT FROM AUTHOR]

Summary: Seroclearance of hepatitis B surface antigen (HBsAg) has been widely studied; however, seroconversion of HBsAg and characteristics of viral load among hepatitis B e antigen (HBeAg)‐negative chronic infection patients after HBsAg lost is not clear. We performed a large‐scale study in a HBeAg‐negative chronic infection cohort to evaluate spontaneous HBsAg seroclearance incidence from October 2012 to April 2017 in Jiangsu province, China. We also elucidated the characteristics of HBsAg seroconversion and hepatitis B virus (HBV) DNA detectability among patients who cleared HBsAg. A total of 2997 HBeAg‐negative chronic infection patients (mean age 52.3 ± 12.9 years at baseline) were included. With 10 519 person‐years of follow‐up, 348 patients successfully spontaneously cleared HBsAg, with an incidence rate of 3.31 per 100 person‐years. Patients with HBV DNA detectable ~1999 IU/mL at baseline had a lower probability of HBsAg seroclearance relative to those with undetectable HBV DNA, with a hazard ratio of 0.31 (95% CI = 0.23, 0.41). HBsAg seroconversion occurred in 37.3% of those patients who cleared HBsAg. The geometric mean of anti‐HBs among those with HBsAg conversion was 79.4 mIU/mL. Female had a higher HBsAg seroconversion rate (P = 0.011). Among those with HBsAg seroclearance, 11.2% still had HBV DNA levels of higher than 100 IU/mL. Patients with higher HBV DNA at baseline had a higher risk of detectable HBV DNA levels even after HBsAg seroclearance (P < 0.001). This study reveals HBsAg seroconversion rates and HBV DNA undetectability epidemiological characteristics of patients with HBsAg seroclearance and suggests that monitoring HBV DNA is needed when managing HBeAg‐negative chronic patients, even after clearing HBsAg. [ABSTRACT FROM AUTHOR]

Summary: Previously, we identified UBE2L3 as a susceptibility gene for chronic hepatitis B virus (HBV) infection through genome‐wide association study. Here, we analysed the association between genetic variants of UBE2L3 and the susceptibility to HBV‐related hepatocellular carcinoma (HCC) and further explored its role in HCC. This case‐control study included 1344 subjects who cleared HBV, 1560 HBV carriers and 1057 HBV‐related HCC patients. Two single nucleotide polymorphisms (SNPs) were genotyped, including rs2266959 and rs4821116. Logistic regression analysis was performed to compute the odds ratio (OR) and 95% confidence interval (CI). We further analysed the expression of UBE2L3 and its association with pathological features based on The Cancer Genome Atlas (TCGA) data and our tissue microarray. Proliferation and migration assays were performed in hepatoma cell lines with or without UBE2L3 knockdown. Further RNA‐seq analysis was performed to explore the underlying oncogenic mechanism. The variant genotypes of rs4821116 in UBE2L3 were associated with decreased risk for HCC and chronic HBV infection. Moreover, based on both TCGA and our tissue microarray data, higher levels of UBE2L3 expression were correlated with higher tumour grade, advanced tumour stage and poor survival. In vitro analysis revealed that UBE2L3 may promote hepatocyte proliferation and migration. RNA‐seq analysis showed that UBE2L3 was inversely correlated with CDKN2B, a negative regulator of cell cycle, and CLDN1, loss of which may promote cancer metastasis. In conclusion, UBE2L3 may also be a susceptibility gene in HBV‐related HCC, and it may promote HCC proliferation and migration by negatively regulating CDKN2B and CLDN1. [ABSTRACT FROM AUTHOR]

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]

Tumor necrosis factor receptor superfamily member 10 (TNFRSF10) is a death domaincontaining receptor for the apoptotic ligand TNFSF10, which involves multiple processes, including hepatocarcinogenesis and immune response against HBV infection. Several single nucleotide polymorphisms (SNPs) were identified as expression quantitative trait loci (eQTLs) for TNFRSF10. To assess the association of TNFRSF10 eQTL SNPs with the risk of hepatocellular carcinoma (HCC) and chronic HBV infection, we designed a case-control study that included 1,300 HBV-related HCC patients, 1,344 chronic HBV carriers, and 1,344 subjects with HBV natural clearance, and then genotyped two TNFRSF10 eQTL SNPs (rs79037040 and rs2055822). We found that rs79037040 GT/TT genotypes were associated with a decreased HCC risk (adjusted odds ratio [OR]=0.83, 95% confidence intervals [CIs] =0.71-0.97, P=0.021) but an increased chronic HBV infection risk of borderline significance (adjusted OR=1.14, 95%CIs=0.98-1.33, P=0.085). In contrast, the rs2055822 G allele was a risk factor for HCC (adjusted OR=1.12, 95%CIs=1.00-1.25, P=0.041) but a protective factor for chronic HBV infection (adjusted OR =0.89, 95%CIs=0.80-0.99, P=0.038). Furthermore, we observed a dose-dependent relationship between the number of alleles (rs79037040-T and rs2055822-A) and the risk of HCC and chronic HBV infection. In comparison with "0" alleles, having "1-4" alleles was significantly associated with decreased HCC risk and increased HBV infection risk. These findings suggest that eQTL SNPs for TNFRSF10 may be susceptibility markers for HCC and chronic HBV infection. [ABSTRACT FROM AUTHOR]

We thank Thomas Worland and colleagues for their comments in our article.[[1]] They pointed out no significant correlation between hepatitis B virus (HBV) activity (both histologically and serologically) and the degree of steatohepatitis on liver biopsy at a single quaternary liver transplant centre. Among the participants without antiviral treatment, compared with participants without fatty liver, those with fatty liver had a lower level of HBV DNA among the whole period of follow-up (F = 12.59, I P i < .001). Fatter liver was persistently associated with lower serum HBV DNA levels, suggesting its potential negative influence on the living space of virus, which was similar with previous studies.[[3]] Furthermore, we found that there were no significant different HBV DNA levels changing trends in partcipants with fatty liver or without. [Extracted from the article]

Interleukin 1β (IL-1β) is a multifunctional cytokine that upregulates the inflammatory response, and participates in carcinogenesis, malignant transformation, tumor growth, invasion and metastasis. Two potentially functional polymorphisms (T-31C and C-511T) in the IL-1β gene promoter were suggested to be correlated with alteration of IL-1β expression and therefore may be associated with cancer risk. To test the hypothesis that these 2 polymorphisms are associated with risk of breast cancer, we performed a case-control study of 365 breast cancer cases, 270 patients with benign breast diseases (BBD) and 631 cancer-free controls in a Chinese population. Multivariate logistic regression analyses revealed that increased risk of breast cancer was associated with IL-1β-31C variant genotypes [adjusted odds ratio (OR) = 1.28 and 95% confidence interval (CI) = 0.91-1.80 for -31CT and 1.72 (95% CI = 1.16-2.54) for -31CC], compared with the -31TT genotype. Similarly, IL-1β-511T variant genotypes were also associated with increased risk of breast cancer (adjusted OR = 1.20, 95% CI = 0.86-1.67 for -511CT and adjusted OR = 1.74, 95% CI = 1.18-2.56 for -511TT), compared with the -511CC genotype. Furthermore, cancer risks associated with IL-1βT-31C variant genotypes were more evident in older women, postmenopausal women and individuals with a later menarche age. Interestingly, although we did not find significant associations of these 2 variants with cancer risk when compared with the BBD patients, a 1.27-fold (95% CI = 1.01-1.60) increased risk was observed with the -31C-511T common haplotype. These findings indicate that these 2 IL-1β promoter variants may contribute to risk of developing breast cancer in the Chinese population. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]