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Background HIF-1α is relevant to inflammation and fibrosis in hepatitis B virus (HBV)-related liver diseases. Thus, we designed a predictive model for decompensated cirrhosis. Methods Peripheral plasma HIF-1α levels were measured in 52 subjects, including 20 patients with HBV-related-compensated-cirrhosis (HBV-CC), 20 patients with HBV-related-decompensated-cirrhosis (HBV-DC) that underwent transjugular intrahepatic portosystemic shunt (TIPS), and 12 healthy controls (HC). Portal plasma HIF-1α levels were detected in HBV-DC patients. The correlation between clinical data and HIF-1α levels was assessed, logistic regression and nomogram were used to develop prediction model. Results Plasma HIF-1α levels were significantly higher in HBV-DC patients than that in HBV-CC patients and healthy controls (DC: 656.34±417.96, CC: 294.23±138.03, HC: 194.63±54.14, pg/ml; P = 0.0004). Plasma HIF-1α levels were positively correlated with total bile acid, total bilirubin, APRI, FIB-4, and MELD scores, and negatively correlated with albumin and platelets. Multivariate logistic regression manifested that total bilirubin (OR = 19.439; 95% CI: 1.486–254.320, P = 0.024), spleen thickness (OR = 75.144; 95% CI: 4.157–1358.440, P = 0.003) and HIF-1α concentrations above 341.78 pg/ml (OR = 23.580; 95% CI: 1.842–301.781, P = 0.015) were markedly associated with HBV-DC and thus included in the nomogram. The terrific cut-off value for the probability of HBV-DC was > 45%, and area under the curve was 0.954 (P < 0.001), with 95% sensitivity and specificity. Conclusions HIF-1α is related to biochemical liver parameters, cirrhosis grade, and progression to HBV-DC. Our model has preferable predictive value for HBV-DC.

The relationship between the serum transforming growth factor (TGF)-β level and HBsAg loss has not been clearly elaborated in patients with chronic hepatitis B (CHB).Two cohorts of patients with CHB were studied. Cohort A: A total of 207 hepatitis B e antigen (HBeAg)-negative CHB patients who finished ≥1 year nucleos(t)ide analogue monotherapy and sequentially received PEGylated interferon treatment for less than 96 weeks were included. Cohort B: Forty HBeAg-positive patients who initially received entecavir therapy for at least 96 weeks were included. Their viral markers and serum TGF-β levels were measured at different time points during therapy.The levels of serum TGF-β and HBsAg (0-24 W) were significantly lower in the patients who had HBsAg0.05 IU/mL at 48 weeks than in patients who did not in cohort A. We got the same results when we further divided the patients into subgroups according to the initial HBsAg cut-off values (1000 IU/mL, 100 IU/mL, 50 IU/mL) in cohort A. However, HBeAg seroconversion did not lead to the downregulation of TGF-β levels. The levels of serum TGF-β were significantly correlated with HBsAg quantitation in cohort A (12-24 W) but not in cohort B (0-48 W). The levels of TGF-β at week 12 could be used as an early index to predict a functional cure (AUC=0.818) as well as the levels of HBsAg itself (AUC=0.882) in HBeAg-negative chronic hepatitis B patients treated with PEGylated interferon.The levels of serum TGF-β were significantly associated with HBsAg loss but not with HBeAg seroconversion and could be used as an early index to predict a functional cure in CHB patients treated with PEGylated interferon.

Background A growing body of evidence suggests that E2Fs, by regulating gene expression related to cell cycle progression and other cellular processes, play a pivotal role in human cancer. However, the distinct roles of each E2F in the development and treatment of hepatocellular carcinoma (HCC) remain unknown. In the present study, the mRNA expression and prognostic value of different E2Fs in HCC are analyzed. Materials and methods Transcriptional and survival data related to E2F expression in patients with HCC were obtained through ONCOMINE and UALCAN databases. Survival analysis plots were drawn with Kaplan–Meier Plotter. The sequence alteration data for E2Fs were obtained from The Cancer Genome Atlas and c-BioPortal. Gene functional enrichment analyses were performed in Database for Annotation, Visualization and Integrated Discovery. Results The mRNA expression levels of E2F1–E2F8 were all significantly upregulated in HCC patients, and high expression of each E2F was obviously related to poor prognosis. Similarly, the expression of E2Fs showed prognostic prediction value in HCC patients with different cancer stages and pathological grades. Moreover, the mutation rate of E2Fs was relatively high in HCC patients, and the DNA sequence alterations primarily occurred in E2F5, E2F3, and E2F6, which were associated with worse overall survival and disease-free survival in HCC patients. Network analysis confirmed that the expression levels of cell cycle-related genes were mostly affected by E2F mutations. Conclusion High expression of individual E2Fs was associated with poor prognosis in all liver cancer patients. E2Fs may be exploited as good prognostic targets for comprehensive management of HCC patients, but this notion should be further evaluated in clinical studies.

Background: Patients with HBV-related acute-on-chronic liver failure (HBV-ACLF) are characterized by immune paralysis and susceptibility to infections. Macrophages are reported to polarize to proinflammatory or anti-inflammatory functional states in different morbid states. However, the molecular mechanisms of macrophage polarization in the disease progression of HBV-ACLF have not yet been elucidated. Aims: To investigate the dynamic macrophage polarization changes in different stages of HBV-related liver disease and explore the potential mechanism of macrophage polarization during HBV-ACLF. Methods: The functional status of peripheral blood mononuclear cells derived from macrophages from patients with mild chronic hepatitis B, HBV-related compensated liver cirrhosis, HBV-related decompensated liver cirrhosis, HBV-ACLF and healthy controls was determined. A transcriptome sequencing analysis was performed to investigate the pathways involved in macrophage polarization in HBV-ACLF. The chloride intracellular channel-3 (CLIC3) gene expression was suppressed in the human monocytic THP-1-derived macrophages to study its role in macrophage polarization. Results: Macrophages exhibited different functional statuses in different stages of HBV-related liver disease. Macrophages were mainly exhibiting an anti-inflammatory phenotype and functional characteristics in patients with HBV-ACLF, which was predictive of a poor clinical outcome. The expression of CLIC3, which is involved in immunological diseases, was reduced in HBV-ACLF patients, indicating a poor prognosis. In addition, CLIC3 could regulate proinflammatory macrophage polarization through the NF-κB and Akt pathways. Conclusion: Macrophage polarization changes dynamically in HBV-related liver diseases. CLIC3 suppression-mediated anti-inflammatory macrophage polarization plays an important role in the progression of HBV-ACLF, and CLIC3 expression is a potential indicator of the prognosis of HBV-ACLF patients. Funding Statement: Supported by the Guangzhou City Science and Technology Project (No. 201607010064), the Natural Fund of Guangdong Province (No. 2016A030313237), the National Science and Technology Major Project (2018ZX10302204) and The National Natural Science Foundation of China (81672701). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: This study was approved by the Third Affiliated Hospital of Sun Yat-Sen University Ethics Committee ([2018]02-432-01). If patients were unable to provide consent, informed consent was obtained from the next of kin.

Accumulating evidences indicate the elevated expression of αB-Crystallin (Cryab) is implicated in tumorigenesis. However, the expression and biologic role of Cryab in osteosarcoma (OS) are still unknown. In this study, we showed that Cryab expression was elevated in OS tissues and cell lines, and down-regulation of Cryab in MG-63 and U-2OS cells led to a decline in the cells' aggressiveness, and reduced secretion of matrix metalloproteinase-9 (MMP-9) in vitro, and lower metastasis potential in vivo. Further study indicated that the Cryab expression was positively associated with the activity of ERK1/2 which is responsible for the cells' aggressiveness and MMP-9 secretion. Clinically, our data confirmed that the high level of Cryab was associated with shorten survival and tumor recurrence for the postoperative OS patients. Together, our results indicate that high level of Cryab is a new adverse outcomes marker for OS patients and may be used as a new therapeutic target.

Depression in patients with chronic hepatitis B (CHB) can affect the quality of life, disease diagnosis and case fatality rate. The aim of this study was to explore depression in patients with CHB and cirrhosis, and the effect of the severity of liver cirrhosis on the depressive emotional state. The depressive emotional state was investigated using the Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) in 114 patients with CHB and cirrhosis, comprising 42 cases classified as Child-Pugh grade (CPG)-A, 38 cases classified as CPG-B and 34 cases classified as CPG-C at a single hepatology center. Patients with mood disorders accounted for 33.33% of the 114 cases with CHB and liver cirrhosis and comprised 10 cases of CPG-A, 12 cases of CPG-B and 16 cases of CPG-C classification. The results shows that HAMA and HAMD scores of patients in the CPG-C group were significantly higher than those in the CPG-A group (P0.05). The incidence rate of mood disorders in the CPG-C group was significantly higher than that in the CPG-B group (P=0.0336), and the incidence rate of mood disorders was higher in the CPG-B group compared with the CPG-A group, but the difference was not statistically significant (P=0.4370). The incidence rate of mood disorders in patients in the CPG-A group was significantly lower than that in the CPG-C group (P=0.0078). The study shows that a considerable proportion of patients with liver cirrhosis have mood disorders, and the depression rates of CHB-infected patients with liver cirrhosis are closely associated with the severity of the cirrhosis.