Tri-typing Of Hepatitis B-related Acute-on-chronic Liver Failure Defined By The World Gastroenterology Organization

BackgroundAcute-on-chronic liver failure(ACLF)is a syndrome characterized by acute clinical deterioration resulting from precipitating factors or non-identifiable triggers in patients with underlying chronic liver diseases,and is associated with organ failures and high short-term mortality.ACLF was first defined by the Asian Pacific Association for the Study of Liver(APASL)as "acute hepatic insult manifesting as jaundice and coagulopathy,complicated by ascites and/or encephalopathy in a patient with or without previously diagnosed chronic liver disease".The European Association for the Study of Liver(EASL)defined ACLF in cirrhotic patients as "an acute deterioration of pre-existing chronic liver disease,usually related to a precipitating event and associated with increased mortality at 3 months due to multisystem organ failure".To further improve the definition of ACLF,the World Gastroenterology Organization(WGO)Working Party established a new definition,which divided ACLF into three categories based on the status of chronic liver disease:type-A for patients without cirrhosis;type-B for well compensated cirrhosis and type-C for previous hepatic decompensation.However,until now,there has been no published data to describe the specific characteristics of the patients in these three groups and thus validate the feasibility of the WGO classification.Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)is a common syndrome with high mortality in Asia;however none of the previously published studies have attempted to validate the WGO’s ACLF working definition.With this large,retrospective and multicenter cohort,we aimed to define the clinical characteristics and prognosis of HBV-related ACLF patients in order to assess and evaluate the classification system proposed by the WGO Working Party.MethodsThis is a retrospective,multi-center study involving five hepatology centers from tertiary hospitals in China.We screened all cirrhotic or non-cirrhotic patients with chronic HBV infection who were hospitalized for acute decompensation(ascites,encephalopathy,gastrointestinal hemorrhage and bacterial infection)or severe injury(serum bilirubin≥5 mg/dL and international normalized ratio≥1.5)between January 2005 to June 2016.Patients who met the EASL-ACLF criteria were recruited and analyzed.The diagnostic criteria used for organ failure were based on the Chronic Liver Failure Consortium(CLIF-C)organ failure score.These patients were then divided into 3 categories based on the WGO definition of ACLF.The sub-groupings depended on whether there was underlying cirrhosis and whether there was a history of previous hepatic decompensation,including noncirrhotic ACLF(type-A),cirrhotic ACLF with good compensation(type-B)and cirrhotic ACLF with previous hepatic decompensation(type-C).For each patient,clinical data were collected during the period of hospitalization,including demographic data,physical examinations,previous episodes of acute decompensation(AD),laboratory data measurements and potential precipitating events.Survival time and information relating to liver transplantation or liver cancer were documented.All patients were followed-up by telephone,or the information of the last clinic visit in cases of no follow-up.Results are presented as frequencies(percentages)for categorical variables,and means(standard deviation)for continuous variables,respectively.For univariate statistical analyses,Chi-square or Fisher’s exact tests were used for categorical variables and the Mann-Whitney’s U test,Kruskal-Wallis test and non-parametric analysis of variance(ANOVA)were used for continuous variables.Mortality rates were estimated as transplant-free mortality.To compare the predictive capability of different prognostic scoring systems,the area under the receiver operating curve(AUROC)was calculated and compared using the Z-test.Kaplan-Meier analysis was then used to compare mortalities across the three types of ACLF.Significance level was set at P<0.05.ResultsA total of 2646 patients with hepatitis B virus infection were screened.586 patientsmet the EASL-ACLF criteria and were enrolled.According to the WGO definition of ACLF,195(33.3%)non-cirrhotic patients were classified as type-A ACLF,262(44.7%)patients with well compensated cirrhosis were classified as type-B ACLF,and the remaining 129(22.0%)patients,with prior AD history,were classified as type-C ACLF.Compared with type-B and type-C ACLF,type-A patients were associated with younger age,the highest platelet counts,the highest aminotransferase levels,the highest serum sodium level,the highest INR level and the most active HBV replications.The type-C ACLF patients had the highest serum creatinine level.The type-A patients had lower rate of antivirus therapy before enrollment.Significantly fewer patients had identifiable precipitating events(PEs).For those with identifiable PEs,hepatitis B virus reactivation was the most commonly documented PEs in type-A patients.Bacterial infections and gastrointestinal hemorrhages were more predominant in type B and C ACLF cases.Liver failure(97.4%)and coagulation failure(86.7%)were most common in type-A compared with type B or C ACLF patients.Kidney failure was predominantly identified in type C subjects(41.9%),and was highest(60.5%)in grade-1 ACLF patients.Furthermore,type-C ACLF showed the highest 28-day(65.2%)and 90-day(75.3%)mortalities,compared with type-A(48.7%and 54.4%,respectively)and type-B(48.4%and 62.8%respectively)ACLF cases.Compared with type-A(11.7%)ACLF patients,the increased mortality from 28-day to 90-day was higher than in type-B(31.6%)and type-C(37.5%).The traditional Model for End-stage Liver Disease(MELD)score and MELD-Na score were superior for the prediction of short-term mortality in type-A ACLF patients.ConclusionTri-typing of HBV-related ACLF in accordance with the WGO’s definition was able to distinguish clinical characteristics and short-term prognosis in ACLF patients.It can be used in the clinical menanagement in ACLF patients.