Chinese Chronic Liver Failure Consortium Acute-on-Chronic Liver Disease and Failure Study --a Prospective Multi-center Study in China, the Largest Hepatitis B Virus High-endemic Region.

Acute-on chronic liver failure (ACLF) was first described by Japanese researchers in 1995. In 2011, the American Association for the Study of Liver Disease (AASLD) and the European Association for the Study of the Liver (EASL) concluded that the core characteristics of ACLF were multiple organ failures and high short-term mortality. In 2013, the EASL-CLIF (the European Association for the Study of The Liver-chronic liver failure) established the CLIF-SOFA (chronic liver failure-sequential organ failure assessment) criteria of ACLF through a prospective multicenter study at 29 liver units in eight European countries for 1 year, with a focus on patients with alcoholic cirrhosis with acute decompensation (AD). In China, patients with acute deterioration of previously chronic liver disease were diagnosed with chronic severe hepatitis, until 2008 these patients had been termed "ACLF", due to the APASL reached a consensus of diagnostic criteria of ACLF. In the Asia-Pacific region, the majority of liver disease is viral hepatitis, while in western countries, it is alcoholic liver disease. There is a sharp east-west divide with respect to the definition of ACLF, especially in the definition of chronic liver disease and its precipitating events.

The investigators analyzed 6 years' data of hepatitis B virus (HBV)-related chronic liver disease in patients with AD in two affiliated hospitals of Shanghai Jiao Tong University School of Medicine. These data were also quantified and sent to the EASL-CLIF centre for analysis. 80% of whole patients were clinically diagnosed with cirrhosis, 30% of which had pathological diagnosis. Through analysis of the liver tissues of the liver transplantation (LT) patients, 95% had pseudolobules. The residual 5% of liver tissues were in the S3 stage of progressive liver fibrosis. Compared with the CANONIC (EASL-CLIF Acute-on-Chronic Liver Failure in Cirrhosis), there are many similarities between ACLF patients with alcoholic cirrhosis or HBV induced cirrhosis: (1)The age of ACLF patients is younger than that of cirrhotic patients with AD. (2)ACLF is exist at any stage of liver fibrosis. (3)The number of organ failures decides the severity of the disease and is related to mortality of the patient. (4) Predisposition to acute liver injury (ALI) does not correlate with the history of the disease and outcome of the patient. (5)The 90-day mortality rate of ACLF is 45-50%, which is obviously higher than that of non-ACLF patients (5%). (6)Eastern and western types of ACLF can have similar SOFA scores as a diagnostic criterion (CLIF-OF or CLIF-SOFA), and a similar prognostic model to predict the outcomes of ACLF and non-ACLF patients. ACLF patients with cirrhosis induced by HBV or alcoholism differ in main types of organ failure. The former group is liver failure (total bilirubin≥12mg/dl) and coagulation failure(international normalized ratio; INR≥2.5), whereas the latter group is renal failure(creatinine≥2mg/dl or use of renal replacement therapy) and nervous system failure(hepatic encephalopathy; HE≥III grade).

Research on hepatic pathology in HBV-induced ACLF patients after LT in RenJi Hospital demonstrated that the pathological characteristics of ACLF may be MHN/SMHN (massive hepatic necrosis/submassive hepatic necrosis) in the background of liver pseudolobules. Regeneration of hepatic progenitor cells, cholestasis, and sepsis are other possible pathological features of ACLF.

It is necessary to conduct a prospective multicentre study to clarify the eastern type of ACLF and the differences between the eastern and western types of ACLF. The investigators are going to identify three key points: (1)Whether HBV and non-HBV ACLFs are belong to a homogenous disease entity which share the same diagnostic criteria, disease grades classification and prognostic model; (2) Whether acute deteriorating patients from cirrhosis or from mild fibrosis (S1-S2) belong to a homogenous entity? (3)To clarify if there are heterogenous groups in APASL criteria diagnosed ACLF patients.

The investigators plan to enroll 2000-3000 consecutive patients from January to December 2015. The research will be carried out in about 14 Chinese national wide liver centers each of whose total beds are around 500.