慢加急性肝衰竭（HBV-ACLF）是一组高病死率的复杂综合症，主要难题是发病机制不清、缺乏统一诊断标准和早期预警预测技术。课题组前期利用多中心、前瞻性大队列研究建立了HBV-ACLF诊断的中国标准，克服了欧洲标准的不足；组建了该大队列患者外周血单个核细胞、血清和血浆全匹配的生物样本库、和小样本mRNA、miRNA和蛋白组测序，发现THBS1和THBD等20个特异性高表达基因与HBV-ACLF进展与高病死率密切相关。本研究拟在前期基础上，利用现有样本库进行大样本mRNA、miRNA测序和蛋白组检测，建立HBV-ACLF不同进展阶段患者多组学匹配的大数据库；利用自建的多组学功能关联分析技术，揭示HBV-ACLF发生、发展及转归等不同阶段的分子特征，发现并鉴定HBV-ACLF早期诊断和预警预测的特异性分子标志物、建立基于组学大数据的精准检测技术，为最终降低HBV-ACLF病死率提供新的技术支持。

Acute-on-chronic liver failure (ACLF) is a complex syndrome that results in a high short-term mortality. Early diagnosis and prognosis for intensive treatment of ACLF is very important to decrease the unacceptably high mortality rate. However, its detailed mechanism is still unclear, and the definition of ACLF based on cirrhosis, irrespective of etiology, remains controversial. Our previous large, prospective, multicenter study clarified the distinct clinicopathological characteristics of patients with hepatitis B-related ACLF (HBV-ACLF) different from those of alcoholic liver disease-related ACLF in Western populations, and developed new evidence-based diagnostic criteria (Chinese Group on the Study of Severe Hepatitis B-ACLF, COSSH-ACLF) and a prognostic scoring system for patients with HBV-ACLF. Regardless of the presence of cirrhosis, patients with chronic hepatitis B, total bilirubin (TB) ≥ 12 mg/dL and an international normalized ratio (INR) ≥ 1.5 should be included in the ACLF definition according the COSSH-ACLF diagnostic criteria. The new prognostic score for short-term mortality was superior to five other scores, based on both discovery and external validation studies. This COSSH-ACLF bridges the gap in the CLIF-ACLF criteria proposed by the Chronic Liver Failure (CLIF) Consortium Acute-On-Chronic Liver Failure in Cirrhosis (CANONIC) of European Association for the Study of the Liver (EASL) for an HBV-ACLF diagnosis. Compared with the EASL-ACLF, the COSSH-ACLF identified approximately 20% more patients with ACLF who can receive earlier clinically intensive management. Base on this previous large, prospective, multicenter study cohort, we have established a HBV-ACLF patient peripheral blood mononuclear cells (PBMC), serum and plasma matched biosample bank. A multi-omics (mRNA, miRNA sequencing and proteomic) data base with small number samples has also been developed. In this study, we aim to establish a new multi-omics based data base for different stages of disease progression in HBV-ACLF, discover the detailed molecular characteristics of disease occurrence, development and prognosis of HBV-ACLF using the functional synergy analysis, develop and validate some specific multi-omics biomarkers-based precise test methods for diagnosis and prognosis of HBV-ACLF.