Chinese Multi-center Clinical Cohort Study On The Diagnostic Criteria And Clinical Course Of Acute Exacerbation Of Chronic Liver Disease Hospitalized Patients With Acute-on-chronic Liver Failure

Acute-on-chronic Liver Failure in China: Rationale for Developing a Patient Registry and Baseline Characteristics Background and aims: Definitions and descriptions Western and Eastern types of acute-on-chronic liver failure(ACLF)are still controvertible,and alcoholism and hepatitis B virus(HBV)are the main aetiologies,respectively.Methods: Fourteen nationwide top liver centres in China enrolled 2600 in-patients with acutely deteriorate chronic liver disease(both cirrhotic and non-cirrhotic)of various aetiologies.They were continuously recruited from January 2015 to December 2016.Data were collected 28 days during hospitalization and continuous follow-ups were performed monthly until 36 months after discharge.A multicentre prospective cohort of 2600 patients finally was designed(NCT no.NCT02457637).Results: Of these patients,71.5% were HBV-related chronic liver disease,1833 had cirrhosis,and 767 had non-cirrhotic disease.The numbers and proportions of enrolled patients from each participating centre,loss of follow-up rate and the baseline characteristics of the patients are presented.Part Two Prognosis Assessment of Acute-on-Chronic Liver Failure in Patients With HBV-Related Cirrhosis Requires Specific CriteriaBackground and aims: The most accepted diagnostic criteria of ACLF have been developed by the European CANONIC study in patients with acutely decompensated(AD)alcoholic or hepatitis C virus-related cirrhosis.We aimed to design diagnostic criteria of ACLF specific for patients with hepatitis B virus(HBV)-related cirrhosis.Methods: Prospective,observational study in 1,402 patients with AD HBV-related cirrhosis admitted at 14 Chinese hospitals using an evidence-based methodology similar to that used for the European CANONIC study.Results: We developed a new 5-variable organ failure(OF)score.Circulatory failure was excluded due to its low(0.9%)prevalence.Definitions of individual OFs(coagulation [INR ≥2],liver [bilirubin ≥22.0 mg/d L],kidney [creatinine ≥1.5 md/d L],respiratory [respiratory support],brain [overt encephalopathy])and ACLF,based on associated mortality and number of OFs,respectively,differed from European definitions.The prevalence of ACLF,ACLF-1(1 OF),ACLF-2(2 OFs)and ACLF-3(3-5 OFs)were 40.9%,25.4%,11.1%,and 4.4%,respectively.The 28-day transplantfree mortality were,respectively,22.0%,11.9%,32.9% and 66.1%;it was 1.8% in patients without ACLF.The relative risk of 28-day mortality of ACLF-1 was 6.6,compared with no ACLF patients.Using either COSSH criteria(developed in HBVrelated cirrhosis but largely based on the CANONIC Criteria)or European CANONIC criteria in our patients resulted in 37.2% and 65.8% false negative and 15.7% and 0.9% false positive diagnoses,respectively.Our criteria were validated in a cohort of 890.Conclusion: ACLF in patients with AD HBV-related cirrhosis requires specific diagnostic criteria.The criteria developed in the European CANONIC study are inaccurate for ACLF diagnosis in these patients.Registration number: NCT02457637.Part Three Clinical course of ACLF in patients with cirrhosis due to chronic hepatitis B virus infection.Predictive factors and prognosis.Background and aims: The Chinese Chronic Liver Failure-Consortium(Ch.CLIF-C)Canonic Study is an observational investigation in 1402 patients with hepatitis B virus(HBV)cirrhosis aimed at investigating Acute-on-Chronic Liver Failure(ACLF).This article reports the clinical course patterns of the syndrome.Methods: Data were obtained at enrolment,4 and 7 days after enrolment and weekly during a 28-day follow-up period.Long-term mortality was also recorded.828 patients had no ACLF and 574 patients had ACLF at enrolment(ACLF-1: 356;ACLF-2: 156;ACLF-3: 62).Results: There were 4 clinical course patterns: 1.ACLF development: 8.6 % of patients without ACLF;2.ACLF improvement: 251 patients(43.7%);ACLF resolution(no organ failure at last assessment)occurred in 186(74.1%)of these patients.3.Steady course(no change in ACLF): 222 patients(38.7%);4.ACLF worsening: 71 patients(12.4 %).In 51% ACLF patients,patterns developed within the first week after enrolment.The 28-day and 90-day survival in ACLF patients with non-severe(no ACLF or ACLF-1 at final assessment)or severe(ACLF-2 and-3) clinical course patterns were 93.6% and 83.1%,and 53.9% and 33.8%,respectively.A new highly accurate score(Ch.CLIF-C Clinical Course score including age,infections,serum bilirubin and INR at enrolment)predicting ACLF clinical course severity(AUROC curve: 0.82)was designed and validated,and a cut-off level was identified classifying patients into high(63.3%)and low risk(12.5%)of severe clinical course development.Conclusion: ACLF in HBV cirrhosis has an extremely variable short-term clinical course,which has a great impact in final prognosis.Severity of clinical course can be accurately predicted at diagnosis by the Ch.CLIF-C Clinical Course score.