Enhanced Demethylation of Interferon-γ Gene Promoter in Peripheral Blood Mononuclear Cells Is Associated with Acute-on-Chronic Hepatitis B Liver Failure

Acute-on-chronic hepatitis B liver failure (ACHBLF) refers to liver failure occurring in patients with chronic hepatitis B (CHB) related liver diseases. Interferon-gamma (IFN-gamma) plays an important role in the exacerbation of liver function. However, the exact mechanism, by which IFN-gamma mediates ACHBLF, is not fully understood. Forty patients with ACHBLF, fifteen patients with CHB and ten healthy controls were included in this present study. ELISA was performed to measure the level of serum IFN-gamma. The methylation status of IFN-gamma promoter in peripheral blood mononuclear cells (PBMCs) was determined using methylation-specific FOR. Model for End-stage Liver Disease (MELD) scoring was performed for evaluating the severity of liver failure. The serum level of IFN-gamma in patients with ACHBLF or CHB was significantly lower than that in healthy controls, while the serum IFN-gamma level in ACHBLF patients was significantly higher than that in CHB patients. In ACHBLF patients, the level of IFN-gamma was positively correlated with total bilirubin and MELD score, but negatively correlated with prothrombin time activity. These results suggest the involvement of IFN-gamma in the pathogenesis of ACHBLF. Importantly, the degree of methylation of the IFN-gamma gene promoter in ACHBLF patients (60%, 24/40) was significantly lower than that in CHB patients (93%, 14/15), but was higher than that in the control group (20%, 2/10). Furthermore, in ACHBLF patients, the serum IFN-gamma level was significantly higher in unmethylation group than that in methylation group. In conclusion, enhanced demethylation of IFN-gamma gene promoter in PBMCs may be associated with the onset of ACHBLF.