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Epithelial cell transformation (EMT) plays an important role in the pathogenesis and metastasis of hepatocellular carcinoma (HCC). We aimed to establish a genetic risk model to evaluate HCC prognosis based on the expression levels of EMT-related genes. The data of HCC patients were collected from TCGA and ICGC databases. Gene expression differential analysis, univariate analysis, and lasso combined with stepwise Cox regression were used to construct the prognostic model. Kaplan–Meier curve, receiver operating characteristic (ROC) curve, calibration analysis, Harrell’s concordance index (C-index), and decision curve analysis (DCA) were used to evaluate the predictive ability of the risk model or nomogram. GO and KEGG were used to analyze differently expressed EMT genes, or genes that directly or indirectly interact with the risk-associated genes. A 10-gene signature, including TSC2, ACTA2, SLC2A1, PGF, MYCN, PIK3R1, EOMES, BDNF, ZNF746, and TFDP3, was identified. Kaplan–Meier survival analysis showed a significant prognostic difference between high- and low-risk groups of patients. ROC curve analysis showed that the risk score model could effectively predict the 1-, 3-, and 5-year overall survival rates of patients with HCC. The nomogram showed a stronger predictive effect than clinical indicators. C-index, DCA, and calibration analysis demonstrated that the risk score and nomogram had high accuracy. The single sample gene set enrichment analysis results confirmed significant differences in the types of infiltrating immune cells between patients in the high- and low-risk groups. This study established a new prediction model of risk gene signature for predicting prognosis in patients with HCC, and provides a new molecular tool for the clinical evaluation of HCC prognosis.

Background: Portal vein thrombosis (PVT) is a relatively common complication of cirrhosis. However, the effect of PVT on the prognosis might not be unequivocal. A systematic review and meta-analysis were performed to investigate the effect of PVT on the prognosis of patients with cirrhosis who have not received a liver transplant. Methods: Three databases, including PubMed, EMBASE, and Cochrane Library, were searched for studies published up to March 2020. The survival or mortality rate of patients with PVT served as the main index to evaluate the prognosis of these patients. Hepatic decompensation served as the index of disease progression. Meta-analyses were conducted using Review Manager software 5.2. Results: Sixteen clinical studies were included and analyzed. PVT was associated with an increased risk of mortality in patients with decompensated cirrhosis. According to the meta-analysis, patients with cirrhosis presenting with PVT had a lower 1-year survival rate than patients without PVT (odds ratio (OR), 0.32; 95% confidence interval (CI), 0.14–0.75; P = .008). The cumulative survival rates were similar between the 2 groups at 3 years (OR, 1.04; 95% CI, 1.00–1.08; P = .06), 5 years (OR, 1.33; 95% CI, 0.71–2.48; P = .38) and 10 years (OR, 1.24; 95% CI, 0.79–1.93; P = .35). PVT was associated with a higher mortality rate in patients with Child-Pugh class B and C disease. A significantly increased risk of death was observed in patients with complete PVT. Patients with both PVT and cirrhosis had a higher rate of decompensation than patients without PVT. Conclusions: The presence of PVT might exert a slight effect on the overall prognosis of patients with cirrhosis. PVT might mainly affect the short-term prognosis by increasing hepatic decompensation events in patients with cirrhosis. However, PVT might not influence the long-term prognosis of patients with cirrhosis.

Background HBeAg seroconversion is an important intermediate outcome in HBeAg-positive chronic hepatitis B (CHB) patients. This study aimed to compare the effect of nucleos(t)ide analogs (NAs) on HBeAg seroconversion in treating CHB with lamivudine, adefovir, telbivudine, entecavir, and tenofovir. Methods Network meta-analysis of NA treatment-induced HBeAg seroconversion after 1-2 years of treatment was performed. In addition, NA treatment-induced HBeAg seroconversion after 3-5 years of treatment was systematically evaluated. Results A total of 31 articles were included in this study. Nine and five studies respectively reporting on 1- and 2-year treatment were included in our network meta-analysis. In addition, 6, 5, and 5 studies, respectively reporting on 3-, 4-, and 5-year treatment were included in our systematic evaluation. Telbivudine showed a significantly higher HBeAg seroconversion rate after a 1 year treatment period compared to the other NAs (odds ratio (OR) = 3.99, 95% CI 0.68-23.6). This was followed by tenofovir (OR = 3.36, 95% CI 0.70-16.75). Telbivudine also showed a higher seroconversion rate compared to the other NAs after a 2 year treatment period, (OR = 1.38, 95% CI 0.92-2.22). This was followed by entecavir (OR = 1.14, 95% CI 0.72-1.72). No significant difference was observed between spontaneous induction and long-term telbivudine treatment-induced HBeAg seroconversion. However, entecavir and tenofovir treatment-induced HBeAg seroconversions were significantly lower than spontaneous seroconversion. Conclusion Long-term treatment with potent anti-HBV drugs, especially tenofovir and entecavir, may reduce HBeAg seroconversion compared with spontaneous HBeAg seroconversion rate. Telbivudine treatment, whether short term or long term, is associated with higher HBeAg seroconversion compared with the other NAs. However, the high rates of drug resistance likely limit the application of telbivudine.

In this study, we investigated the roles of T follicular helper (TFH) cells and related molecules in the pathogenesis of chronic hepatitis B virus (HBV) infection. The levels of circulating TFH cells and their surface CD40 ligand (CD40L), as well as CD19(+) B cells and their surface CD40 expression were detected by flow cytometry. Peripheral blood plasma interleukin (IL)-21 levels were detected by enzyme-linked immunosorbent assay (ELISA). Compared with hepatitis B surface antibody (HBsAb)(-) and HBsAb(+) healthy controls, the percentage of TFH cells and their surface CD40L expression significantly increased in patients with chronic HBV infection, particularly those with chronic hepatitis B (P0.05). The percentage of CD19(+) B cells significantly increased in chronic hepatitis B patients and CD40 expression levels on the CD19(+) B cell surface in chronic HBV infection decreased compared with those in the healthy controls (P0.05). Compared with the healthy controls, the plasma IL-21 level in chronic hepatitis B patients was significantly increased in chronic HBV carriers and decreased in inactive hepatitis B surface antigen (HBsAg) carriers (P0.05). The TFH cell percentage, B cell percentage and IL-21 expression did not significantly differ between the hepatitis B e-antigen (HBeAg)(-) and HBeAg(+) chronic hepatitis B groups (P0.05). The abnormal expression of TFH cells and IL-21 is related to the dysfunction of immune response during chronic HBV infection. The interaction of CD19(+) B cells with TFH cells via their CD40 and CD40L molecules may also play an important role in this process.