Circulating cell death biomarker: good candidates of prognostic indicator for patients with hepatitis B virus related acute-on-chronic liver failure

Investigations on survival of patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) are sparse and urgently needed. The current study aimed to evaluate the prognostic value of circulating cell death biomarkers (M30-anigen, M65-antigen and HMGB1) for HBV ACLF. In this prospective study (2/2013-8/2014), 94 patients including 54 HBV-ACLF and 40 chronic hepatitis B (CHB) patients were recruited. 40 healthy controls (HC) were also recruited. HBV-ACLF were followed up for 3 months for short-term mortality. All three biomarkers were significantly elevated in HBV-ACLF compared with CHB or HC. M30- and M65-antigens could significantly discriminate between non-survivors and survivors in HBV-ACLF. However, HMGB1 showed no prognostic value. By Cox regression analysis, M30- and M65-antigens and MELD were identified as independent predictors for short-term mortality. A novel prognostic model, MELD-CD (MELD-cell death) was established based on the multivariate results. The adjusted Harrell's C-index of MELD-CD was 0.86 (P < 0.001) and was significantly higher (P < 0.001 for all) than the currently used models, MELD (C-index, 0.71, P < 0.001), MELD-NA (0.67, P < 0.001), CTPs (0.61, P < 0.05). Dynamic analyses further confirmed the prognostic utility of M30- and M65-antigen. Future studies are warranted to validate the results.