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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]

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]

. 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]

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]