Tumor metastasis is responsible for the high mortality rates in patients with hepatocellular carcinoma (HCC). Absent in melanoma 2 (AIM2) has been implicated in inflammation and carcinogenesis, although its role in HCC metastasis remains unknown. In the present study, we show that AIM2 protein expression was noticeably reduced in HCC cell lines and clinical samples. A reduction in AIM2 was closely associated with higher serum AFP levels, vascular invasion, poor tumor differentiation, an incomplete tumor capsule and unfavorable postsurgical survival odds. In vitro studies demonstrated that AIM2 expression was modulated by hepatitis B virus X protein (HBx) at transcriptional and post‐translational levels. HBx overexpression markedly blocked the expression of AIM2 at mRNA and protein levels by enhancing the stability of Enhancer of zeste homolog 2 (EZH2). Furthermore, HBx interacted with AIM2, resulting in an increase of AIM2 degradation via ubiquitination induction. Functionally, knockdown of AIM2 enhanced cell migration, formation of cell pseudopodium, wound healing and tumor metastasis, whereas reintroduction of AIM2 attenuated these functions. The loss of AIM2 induced the activation of epithelial‐mesenchymal transition (EMT). Fibronectin 1 (FN1) was found to be a downstream effector of AIM2, with its expression reversely modulated by AIM2. Silencing of FN1 significantly halted cell migration induced by AIM2 depletion. These data demonstrate that HBx‐induced loss of AIM2 is associated with poor outcomes and facilitates HCC metastasis by triggering the EMT process. The results of the present study therefore suggest that AIM2 is a potential prognostic biomarker in hepatitis B virus‐related HCC, as well as a possible therapeutic target for tumor metastasis.

Hepatocyte nuclear factor 4 alpha (HNF4α) plays an important role in tumourigenesis. There is growing evidence indicating that HNF4α transcribed by promoter 1 (P1-HNF4α) is expressed at relatively low levels in HCC and its presence predicts a favourable outcome for hepatocellular carcinoma (HCC) patients. However, the role of HNF4α transcribed by promoter 2 (P2-HNF4α) in HCC remains unclear. A total of 615 HCC specimens were obtained to construct tissue microarrays and perform immunohistochemistry. The relationship between P2-HNF4α and clinical features of HCC patients were analysed. Kaplan–Meier analysis was conducted to assess the prognostic value of P2-HNF4α. The results showed that the expression of P2-HNF4α in HCC was noticeably increased in HCC tissues compared with the nontumourous tissues. In addition, P1-HNF4α expression was negatively correlated with P2-HNF4α expression (p = 0.023). High P2-HNF4α expression was significantly associated with poor differentiation of HCC (p = 0.002) and vascular invasion (p = 0.017). Kaplan–Meier analysis showed that P2-HNF4α expression was closely correlated with overall survival in the training group (p = 0.01), validation group (p = 0.034), and overall group of patients with HCC (p < 0.001). Our data show that the role of HNF4α in cancer development needs to be further refined. P2-HNF4α, different from P1-HNF4α, is markedly upregulated and serves as an oncogene-associated protein in HCC. Our study therefore provides a promising biomarker for prognostic prediction and a potential therapeutic target for HCC.

Background: We investigated whether metabolic syndrome exacerbated the risk of liver fibrosis among chronic hepatitis B patients and risk factors associated with liver steatosis and fibrosis in chronic hepatitis B patients with components of metabolic syndrome.Methods: This study included 1236 chronic hepatitis B patients with at least one component of metabolic syndrome. The controlled attenuation parameter and liver stiffness, patient information and relevant laboratory data were recorded.Results: Controlled attenuation parameter was increased progressively with the number of metabolic syndrome components (p < 0.001). Multivariate analysis indicated younger age, high gamma‐glutamyltransferase level, high waist‐hip ratio, and high body mass index were independent risk factors associated with nonalcoholic fatty liver disease among chronic hepatitis B patients with metabolic syndrome. In the fibrosis and non‐fibrosis groups, most of blood lipid was relatively lower in fibrosis group. An increased proportion of chronic hepatitis B patients with liver fibrosis was found concomitant with an increasing number of components of metabolic syndrome. Male gender, older age, smoking, aspartate aminotransferase levels, high body mass index, and low platelet level were identified as independent risk factors associated with liver fibrosis.Conclusions: For chronic hepatitis B patients with coexisting components of metabolic syndrome, stratification by independent risk factors for nonalcoholic fatty liver disease and fibrosis can help with management of their disease.

Health-related quality of life in patients with chronic hepatitis B during antiviral treatment and off-treatment Xiulan Xue,1,* Shaohang Cai,1–3,* Hongjie Ou,1 Caixia Zheng,1 Xiaolu Wu1 1Department of Infectious Diseases, First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, 2Department of Pathology, Sun Yat-sen University Cancer Center, 3State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong Province, People’s Republic of China *These authors contributed equally to this work Introduction: Health-related quality of life (HRQoL) has emerged as an important consideration in the care of patients with chronic hepatitis B (CHB). However, whether benefits from the improved HRQoL that occurs after antiviral treatment or drug discontinuation outweigh the risks of viral relapse is an unanswered question. The aim of this study was to evaluate the HRQoL among patients with CHB during antiviral treatment and withdrawal of treatment. Patients and methods: There were 102 patients who met the enrollment criteria with 54 patients in the treatment group and 48 patients in the discontinuation group. Sociodemographic information was collected. The 36-Item Short-Form Health Survey (SF-36), European Quality of Life-5 Dimensions, and Beck Depression Inventory (BDI) were adopted to evaluate life quality and mental health. Results: In the treatment group, SF-36 showed that the physical functions were significantly increased. In the discontination group, the psychological functions showed improvement. A multivariate regression analysis indicated that baseline SF-36 score was a predictor for improvement in HRQoL (odds ratio =1.17, P=0.003) and baseline BDI score was a factor for remission of depression (odds ratio =0.75, P=0.005) after medical intervention. When the cutoff value of SF-36 score was set at 79.5, the sensitivity and specificity to predict improvement in HRQoL were 82.8% and 74.0%, respectively. When the cutoff value of BDI was found as 8.5, the sensitivity and specificity to predict alleviation of depression were 58.6%, and 76.0%, respectively. Conclusion: Antiviral treatment benefits the physical health of the patients with CHB, while conferring no obvious improvement in their psychological condition. Improved psychological interventions for patients with CHB, especially for those with lower baseline SF-36 scores and higher BDI scores, may improve their quality of life. Keywords: chronic hepatitis B, health-related quality of life, antiviral treatment, mental disorder, depression

Background: Patients with chronic hepatitis B virus (HBV) infection who are hepatitis B virus e antigen (HBeAg) positive are increasingly being treated with nucleos(t)ide analogs (NUCs). However, the predictive value of serum hepatitis B virus core antibody (HBcAb) levels for HBeAg seroconversion among patients with high viral load remains unclear. Methods: This study consisted of 74 patients with high viral load (HBV DNA >1 × 10⁷ copies/mL) enrolled in a multicenter, randomized, controlled trial, treated with lamivudine and adefovir (N = 32) or entecavir (N = 42) for up to 96 weeks. Serum HBV DNA, quantitative hepatitis B virus surface antigen (HBsAg), HBeAg, and HBeAb was tested at each visit. Quantitative HBcAb evaluation was conducted for all the available samples in the trial, by using a newly developed double-sandwich anti-HBc immunoassay. Results: Serum HBcAb levels were significantly higher in patients with a serum alanine aminotransferase (ALT) level more than five times the upper limit of normal (ULN) compared with patients with ALT levels within 5 × ULN (4.25 ± 0.61 vs. 3.94 ± 0.47 log₁₀ IU/mL, P = 0.0345). Patients with HBeAg seroconversion were associated with a higher level of HBcAb at baseline, compared with those without HBeAg seroconversion (4.38 ± 0.54 vs. 4.02 ± 0.58 log₁₀ IU/mL, P = 0.029). The area under receiver operating characteristic curve of baseline HBcAb for HBeAg seroconversion was 0.71 (95% CI: 0.55–0.86, P = 0.013). When the baseline HBcAb level was >4.375 log₁₀ IU/mL, the sensitivity and specificity to predict HBeAg seroconversion at week 96 were 62.5% and 74.2%, and the positive likelihood ratio (LR) and negative LR were 2.42 and 0.51, respectively. The multivariate analysis result indicated that baseline serum HBcAb level was the only independent predictor for HBeAg seroconversion at week 96, with an odds ratio of 4.78. Conclusion: Baseline serum HBcAb level >4.375 log₁₀ IU/mL could satisfactorily predict HBeAg seroconversion among patients with high viral load treated with NUC.