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. The human La (hLa) protein functions in RNA metabolism and is activated by casein kinase 2 (CK2) phosphorylation. Hepatitis B virus (HBV) can exploit hLa to stabilize its RNA and promote its pathogenesis. To enhance our knowledge of host molecular pathways involved in HBV pathogenesis, a bioinformatic approach was used to generate an expression profile of all predicted target genes of CK2-activated hLa in HBV-infected cells. A computerized literature search was performed to identify English language studies of HBV-, hLa- and CK2-related molecules. The data were pooled and the genes were classified in three functional groups by gene ontology (GO) analysis. HBV, hLa and CK2 targets were predicted, respectively, by a computational method, followed by screening for matching gene symbols in the NCBI human sequences, GO, pathway and network analyses. hLa targets and respective networks in the viral mechanisms of HBV were obtained by the final integrative analysis. Thirty-seven hub genes were identified by overlap calculation, suggesting that hLa may play an important role in the development and progression of HBV through cytokine-cytokine receptor interaction, hematopoietic cell lineage, cell adhesion molecules (CAMs), antigen processing and presentation, Jak-STAT signalling pathway, natural killer cell-mediated cytotoxicity, apoptosis, T-cell receptor signalling pathway, complement and coagulation cascades, protein export and other pathways. Our data may help researchers to predict the molecular mechanisms of hLa in the development and progression of HBV through CK2 comprehensively. Moreover, the present data indicate that hLa targets may be a series of promising candidates for HBV. [ABSTRACT FROM AUTHOR]

Singapore has a relative higher prevalence of Hepatitis B carriage at 3.6%. The risk of Hepatitis B virus (HBV) flare which is increased in patients receiving anthracycline chemotherapy has clinical relevance due to associated morbidity. Guidelines recommend a risk-adaptive screening strategy. This study aims to analyze the practice of HBV screening, and incidence of flare among non-metastatic breast cancer patients treated with anthracyclines. This is a retrospective review of all non-metastatic breast cancer in the Joint Breast Cancer Registry (JBCR) treated with (neo)adjuvant doxorubicin based therapy between August 2015 and December 2016, across 3 tertiary institutions in Singapore. We examined data collected prior to chemotherapy initiation regarding HBV status, including liver function (LFT), HBV surface antigen (HBsAg), antibody to HBV (Anti HBs), HBV core total antibody (Anti HBc) and HBV deoxyribonucleic levels (HBV DNA). We reviewed the course of HBV carriers (HBsAg positive) or prior HBV exposed patients (Anti HBc total positive and HBsAg negative) during chemotherapy for any HBV flare (abrupt rise of alanine aminotransferase levels to more than 5 times upper limit of normal in a carrier). 492 early breast cancer patients were examined. 484 (98.3%) had HBsAg, 159 (32.3%) had Anti HBs and 16 (3.3%) had Anti HBc performed prior to starting chemotherapy. There were 12 HBV carriers and 4 with previous HBV exposure. Among the 12 HBV carriers, 4 were on antivirals prior to the diagnosis of breast cancer, and 8 were started on antivirals following diagnosis. 1 patient received doxorubicin prior to starting antivirals and developed HBV flare after the first cycle. The patient was started on entecavir, with improvement in HBV DNA levels and LFT, and chemotherapy was resumed. Remaining carriers did not develop flares. The patients with prior HBV exposure were monitored with serial LFT, and did not develop transaminitis. Patients are almost universally screened for HBV with HBsAg prior to anthracyclines. Our data was consistent with local carriage rate. The incidence of flare is low with appropriate antiviral prophylaxis. HBsAg alone may be sufficient for screening. The authors. Has not received any funding. All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Suppressor of cytokine signalling 1 ( SOCS1) was demonstrated to play an important negative role in fulminant hepatitis and might be involved in acute-on-chronic hepatitis B liver failure (ACHBLF). This study was therefore to identify the potential role of SOCS1 and its promoter methylation pattern in ACHBLF patients. Sixty ACHBLF patients, 60 chronic hepatitis B (CHB) patients and 30 healthy controls were investigated in this study. We found that expression of SOCS1 mRNA in CHB and ACHBLF patients was significantly higher than that in healthy controls. The serum level of IL-6, IFN- γ and TNF- α was significantly higher in ACHBLF than CHB. Increased serum level of IL-6, IFN- γ and TNF- α was correlated with total bilirubin, ALT, PTA and MELD scores in ACHBLF. The degree of methylation of the SOCS1 in ACHBLF patients (35.0%, 21/60) was significantly higher than that in CHB patients (16.7%, 10/60). Furthermore, methylated group showed lower level of SOCS1, and higher MELD scores and mortality rate when compared with unmethylated group of ACHBLF. These results suggested that SOCS1 might contribute to immune-related liver damage in ACHBLF, and its aberrant methylation may be a key event for the prognosis of ACHBLF. [ABSTRACT FROM AUTHOR]

Aims: A hepatoma cell line, HepG2, was used as a model system to detect Toll-like receptor (TLR) expression in hepatocytes and examine the antiviral effect on hepatitis B virus (HBV). Methods and Results: Toll-like receptor expression was detected in HepG2 cells by RT-PCR. The TLRs, which were strongly expressed in HepG2 cells, were stimulated with specific ligands. Interferon (IFN) response was evaluated poststimulation with Western blotting for signal transduction and activators of transcription-1. Furthermore, HepG2 cells were transiently transfected with wild-type HBV 1·3-fold over-length plasmid and treated with specific ligands at indicated times. Replication of HBV DNA, transcription of HBV RNA intermediate and expression of HBV antigens were respectively detected by Southern blotting, real time PCR, ELISA and Western blotting. Activation of different TLRs induced antiviral effects on HBV to varying degrees. Conclusions: The TLRs, which were strongly expressed in HepG2 cells, could be stimulated with specific ligands. Activation of TLRs induced apparent production of antiviral cytokines such as IFN-α/β and inhibited HBV lifecycle in the hepatocyte cell model. Significance and Impact of the Study: Expression of TLRs in hepatocytes may be related to local immunity of liver and participate in the outcome of viral hepatitis. [ABSTRACT FROM AUTHOR]

Background: Lymphoma combined with hepatitis B infection occupies a relatively higher incidence in China than that of in Europe and America.Aims: To observe the efficacy and safety of rituximab in combination with chemotherapy in patients with B-cell non-Hodgkin's lymphoma (NHL) and hepatitis B virus (HBV) infection.Methods: Ninety-two B-cell lymphoma patients with HBV infection in Sichuan Cancer Hospital from January 2009 to October 2015 were divided into two groups. Patients in Group A (n = 33) were treated with rituximab combined with chemotherapy, while Group B (n = 59) accepted chemotherapy alone.Results: The effective rate (complete response + partial response) was 69.7% in Group A and 44.1% in Group B with significantly statistical difference (P = 0.018). Some of the patients got different grades of hepatic function damage during the period of chemotherapy, but there was no statistically significant difference between these two groups (P = 0.071).Conclusions: For CD20-positive NHL patients complicated with HBV infection, rituximab combined with chemotherapy modality is effective. The promise efficacy of this regimen could be achieved relying on controllable safety based on antiviral treatment. [ABSTRACT FROM AUTHOR]

Background Glutathione-S-transferase P1 (GSTP1) methylation has been demonstrated to be associated with oxidative stress induced liver damage in acute-on-chronic hepatitis B liver failure (ACHBLF). Aim To evaluate the methylation level of GSTP1 promoter in acute-on-chronic hepatitis B liver failure and determine its predictive value for prognosis. Methods One hundred and five patients with acute-on-chronic hepatitis B liver failure, 86 with chronic hepatitis B (CHB) and 30 healthy controls (HC) were retrospectively enrolled. GSTP1 methylation level in peripheral mononuclear cells (PBMC) was detected by MethyLight. Clinical and laboratory parameters were obtained. Results GSTP1 methylation levels were significantly higher in patients with acute-onchronic hepatitis B liver failure (median 16.84%, interquartile range 1.83-59.05%) than those with CHB (median 1.25%, interquartile range 0.48-2.47%; P < 0.01) and HC (median 0.80%, interquartile range 0.67-1.27%; P < 0.01). In acute-onchronic hepatitis B liver failure group, nonsurvivors showed significantly higher GSTP1 methylation levels (P < 0.05) than survivors. GSTP1 methylation level was significantly correlated with total bilirubin (r = 0.29, P < 0.01), prothrombin time activity (r = -0.24, P = 0.01) and model for end-stage liver disease (MELD) score (r = 0.26, P = 0.01). When used to predict 1- or 2-month mortality of acute-on-chronic hepatitis B liver failure, GSTP1 methylation showed significantly better predictive value than MELD score [area under the receiver operating characteristic curve (AUC) 0.89 vs. 0.72, P < 0.01; AUC 0.83 vs. 0.70, P < 0.05 respectively]. Meanwhile, patients with GSTP1 methylation levels above the cutoff points showed significantly poorer survival than those below (P < 0.05). Conclusions Aberrant GSTP1 promoter methylation exists in acute-on-chronic hepatitis B liver failure and shows high predictive value for short-term mortality. It might serve as a potential prognostic marker for acute-on-chronic hepatitis B liver failure. [ABSTRACT FROM AUTHOR]

The cessation criteria for lamivudine treatment vary in published articles and their results are contradictory, especially factors predicting relapse. To clarify these contradictions, this long-term follow-up study of 125 Chinese hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients was designed with stringent cessation criterion. All patients received lamivudine and achieved HBeAg seroconversion (group A, n = 82) or loss (group B, n = 43) with undetectable hepatitis B virus (HBV) DNA by PCR assay during the treatment. Lamivudine was withdrawn ≥6 months after HBeAg seroconversion/loss occurred. The median treatment durations were 24 (12–54) months and 36 (18–89) months in group A and group B, respectively. Patients were followed up for median 24 (2–84) months. The cumulative relapse (defined as serum HBV DNA ≥104 copies/mL) rates in the two groups at months 12, 24, 36 and 48 were 23.4% vs 35.0%, 25.0% vs 37.7%, 25.0% vs 41.1% and 29.4% vs 41.1%, respectively (log-rank test, P = 0.119). For patients whose total treatment duration ≥18 months in group A, the cumulative relapse rates at months 12, 24, 36 and 48 were 18.3%, 20.1%, 20.1% and 25.1%, which was significantly lower than those with a shorter duration (log-rank test, P = 0.002). The mean age and median total duration were statistically different between relapsers and nonrelapsers in group A (33.9 ± 13.6 vs 23.1 ± 11.0 years, P < 0.001 and 24 vs 26 months, P = 0.003). Cox regression revealed that age was the only predictive factor for relapse (RR, 1.069; 95% CI, 1.032–1.106, P < 0.001). Patients aged <30 years relapsed less frequently in 5 years (12.3% vs 53.5%, P = 0.001). In conclusion, for patients who maintained HBeAg seroconversion for ≥6 months and total duration for ≥18 months, lamivudine withdrawal is a reasonable option. Prolonged treatment may be required for patients aged greater than 30 years to reduce relapse. [ABSTRACT FROM AUTHOR]