Diagnostic Criteria Recommendations for Acute-on-Chronic Liver Failure Caused by Combination of Hepatitis B Virus and Alcohol

Objective: There is no consensus on the diagnostic criteria for acute-on-chronic liver failure (ACLF) caused by combination of hepatitis B virus (HBV) infection and alcohol. The aim of this study was to describe the characteristics of deaths occurring in patients with this condition, and then to evaluate the efficacy of different diagnostic criteria for ACLF caused by combination of HBV infection and alcohol. Design: Subjects were sourced from two multi-centre prospective Chinese cohorts (CATCH-LIFE investigation & validation cohorts). Patients with acute-on-chronic liver disease (AoCLD) whose etiology were identified as HBV (HBV-AoCLD), alcohol (alcohol-AoCLD), or combination of HBV and alcohol were included. Results Out of 2898 enrolled patients, 2225 had HBV-AoCLD, 339 had alcohol-AoCLD, and 334 had AoCLD caused by combination of HBV and alcohol. Patients who died in HBV-AoCLD and HBV/alcohol combination groups had similar admission characteristics. Age, total bilirubin, international normalised ratio, albumin, hepatic encephalopathy and ascites were independent risk factors for 28-day mortality in AoCLD caused by HBV and alcohol. For ACLF caused by HBV and alcohol, the COSSH ACLF criteria outperformed the EASL-CLIF ACLF criteria and APASL ACLF criteria in predicting 28-/90-/365-day mortality with significantly higher sensitivity and negative predictive value. Regardless of occurrence of liver cirrhosis or decompensated cirrhosis, occurrence of liver failure with concomitant failure of extrahepatic organ was associated with short-term mortality; the 28-day cumulative mortality rate exceeded 33%. Conclusions: Similar with HBV-AoCLD, the short-term mortality of AoCLD caused by combination of HBV and alcohol is mainly attributable to acute liver damage or liver plus coagulation system failure. Our results suggest that the COSSH standard can be used as diagnostic criteria for ACLF caused by combination of HBV and alcohol. Trial Registration: This study was registered it at www.clinicaltrials.org (NCT02457637, NCT03641872). Funding: This work was sponsored by the National Science and Technology Major Project (2018ZX10723203 and 2018ZX100302), the National Natural Science Foundation of China (grants No. 81972265, 81900579)，the National Natural Science Foundation of Jilin Province (20200201324JC, 20200201532JC), and the Chongqing Natural Science Foundation (CSTC2019jcyj-zdxmX0004). Declaration of Interest: The authors declare no conflict of interest. Ethical Approval: The ethics committee of the Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University (China) approved the study.