A Prospective Multi-center Validating Cohort for ACLF Diagnosis and Prognosis From Ch-CANONIC Study

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 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 related organ failure.

In 2014, investigators had 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 center 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 pseudo-lobules. The residual 5% of liver tissues were in the S3 stage of progressive liver fibrosis. Moreover, the research also demonstrated that the pathological characteristics of ACLF may be MHN/SMHN (massive hepatic necrosis/submassive hepatic necrosis) in the background of liver pseudo-lobules. Regeneration of hepatic progenitor cells, cholestasis, and sepsis are other possible pathological features of ACLF.

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.But ACLF patients with cirrhosis induced by HBV or alcoholism differ in main types of organ failure. According to CLIF-C OFs (CLIF-C organ failure score), the incidence of 6 organ failures is not exactly the same in the two types of ACLF. Even for the same type of organ failure, the short-term mortality of patients is different.

To determine whether there are unified diagnostic criteria, disease grades classification and prognostic model for different etiologies of ACLF, Investigators had launched a multicenter prospective cohort with the same inclusion criteria and disease indicators as those used in the European CANONIC study in China，the Ch-CANONIC study (NCT02457637). The research was carried out in 14 Chinese national wide liver centers each of whose total beds are around 500. From Jan 2015 to Dec 2016, 2600 inpatients with chronic liver disease (including chronic liver hepatitis patients without cirrhosis, compensated cirrhosis patients, decompensated cirrhosis, non-alcoholic fatty liver disease or alcoholic liver disease patients) complicated with AD [acute decompensation): including [(having ascites, hepatic encephalopathy, bacterial infection, gastrointestinal bleeding or jaundice (TB>5NL) within 1 month before enrollment] and/or ALI [acute liver injury: including ALT>3NL (normal level), AST>3NL or TB>2NL within 1 week before enrollment] were recruited. Data were collected during a 28-day hospitalization and continuous follow-ups were performed once a month until 36 months after hospital discharge. Of these patients, 71.5% (1859/2600) had HBV-related disease,71.5% (1833/2600) had cirrhotic disease, and 28.5% (767/2600) had non-cirrhotic disease.

Up to now, every recruited patient has been followed-up for at least 18 months. Thus, a large amount of data has been collected for analysis. The preliminary results of our research are as follows (As the relevant papers are being reviewed, the detailed data will be updated in subsequent protocols):