Abstract: Objective To investigate the apoptotic level of hepatocytes in patients with chronic hepatitis B virus (HBV) infection at different stages, and to evaluate its prognostic value on HBV-related acute-on-chronic liver failure (HBV-ACLF). Methods A prospective study was carried out in 174 patients including 40 chronic hepatitis B (CHB), 40 HBV-related liver cirrhosis (HBV-LC), 54 HBV-ACLF patients and 40 healthy controls (HC). HBV-ACLF group were followed up for 3 months and classified into survival and death group. Apoptotic levels of hepatocytes were measured by detecting keratin-18 associated caspase-cleaved fragment, M30-antigen. Results Serum M30-antigen levels in CHB, HBV-LC and HBV-ACLF were 145.24 [interquartile range (IQR 86.31-206.39) U/L, 213.42 (IQR 147.30-391.28) U/L and 762.67 (IQR 492.45-1395.24) U/L respectively, which were significantly (P<0.01) higher than those in HC group [60.34 (IQR 50.58-67.64)U/L]. Moreover, serum M30-antigen levels were gradually elevated as disease severity increased, reaching to peek in HBV-ACLF group, which was significantly higher (P<0.01) than those in CHB and HBV-LC group. M30-antigen level was significantly positively correlated with alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBil), prothrombin time (PT), international normalized ratio (INR) and HBV-DNA (all P<0.01), while reversely correlated with albumin (P<0.01). More importantly, serum levels of M30-antigen in the death group [1175.18 (IQR 756.57-3224.94) U/L] were significantly (P<0.01) higher than those in the survival group [491.39 (IQR 264.23-657.17) U/L]. Receiver operating characteristic (ROC) curve analysis demonstrated that serum M30-antigen could well predict 3-month outcome of HBV-ACLF patients, as the area under the curve (AUROC) was 0.86 (95% CI 0.75-0.96, P<0.01). Conclusion Hepatocyte apoptosis is closely associated with the disease severity of chronic HBV infection and markedly elevated in patients with HBV-ACLF. Hepatocytes apoptosis biomarker, M30-antigen, might be a potential indicator for the early prognosis of HBV-ACLF.

Key words: Acute-on-chronic liver failure, Hepatitis B virus, Apoptosis, Prognosis