The Prognosis Of Different Subtypes Of HBV-related ACLF And Risk Prediction

OBJECTIVEAlthough the term of acute on chronic liver failure(ACLF)has been recognized for over last two decades.Until now,there is no universal consensus of for the clearly definition.Controversy persists between the Asian Pacific Association for the Study of the Liver(APASL)and European Association for the Study of the Liver-Chronic Liver Failure(EASL-CLIF)Consortium regarding whether patients with background chronic liver diseases including hepatitis with no cirrhosis and decompensated cirrhosis should be covered by ACLF.Recently classification proposed by the World Gastroenterology Organization(WGO)divided ACLF into 3 subtypes according to the chronic status of the liver disease,is promising to unify the different definitions.But prognosis of the 3 subtypes are not well investigated,and even relative data in some previous studies were quite controversial.This study aimed to identify whether the clinicopathological characteristics,especially short-medium mortalities,were homologous between different subtypes of hepatitis B virus(HBV)-related ACLF,and verify the applicability of prognosis scores in the subtypes.METHODS720 hospitalized patients with acute decompensation of cirrhosis or severe liver injury due to HBV in two Chinese centers(the First Affiliated Hospital of Suchow University and Xijing Hospital of the Air Force Medical University)were enrolled.ACLF was diagnosed according to EASL-CLIF criteria with the exception of the diagnostic indicator of cirrhosis,and was categorized depending on whether or not there is underlying cirrhosis(with no cirrhosis,type A),and in patients with cirrhosis,whether or not there is a history of previous hepatic decompensation(compensation cirrhosis,type B and decompensation cirrhosis,type C).The grade of ACLF was evaluated by the types and numbers of organ failure and defined as ACLF grade 1:a single non-renal organ failure with renal dysfunction and/or cerebral dysfunction;or single kidney failure;ACLF grade2:failure of two organs;and ACLF grade 3:with three or more failed organs.The baseline clinical characters including age,sex,insults,etiologies,laboratory parameters,and organ failure features were compared between the 3 types.Prognosis between 3 subtypes including 28-day,90-day and 1-year transparent free mortalities were compared,and further investigated by survival analysis.The predictive abilities of four frequently-used prognosis models including CTP scores,MELD scores,EASL-C OFs,and EASL-C ACLFs were compared by area under ROC curve(AUC)between the 3 subtypes in 28days,90days and 1year.RESULTS1)275 patients met the ACLF criteria of EASL-CLIF,with 73 type A,117 type B and 85 type C.Patients with type A ACLF(44.2±14.2)were younger than those categorized as type B(48.3 ±13.6,p<0.05)and type C(49.1 ±12.2,p<0.05).Flare-up of HBV is the most common acute insults in type A patients(63%),and only 12%patients were induced by bacterial infection.While in type B and type C,the proportion of patients induced by upper gastrointestinal bleeding and bacterial infection were more common,especially infection in type C(32%).Compared to Type-B and Type-C,patients with Type-A ACLF had higher WBC and aminotransferase levels.While serum levels of total bilirubin and coagulation parameters were same between 3 subtypes.And serum levels of platelets and albumin significantly decreased from Type A to Type C.The organ failure types and numbers are nearly same between 3 subtypes,and distributions of Grade 1 to 3 were also similar(p=0.731),with the proportion of the most severe Grade 3 21%,16%and 18%respectively in the 3 subtypes.2)The 28-day(34%,35%and 41%,p=0.595)and 90-day(46%,52%and 56%,p=0.461)transplant free mortalities had no significant difference between the 3types.Patients with type A ACLF(49%)trended to a lower 1-year transplant free mortalities than type B(59%)and type C(64%)with p value more than 0.05,while patients with type B and type C were quite similar(p>0.1).The results of K-M survival curves in different endpoint time were similar to the mortality results.3)Each Grade of ACLF had similar 28-day and 90-day transplant free mortalities no matter what the subtype is,and significantly increased from Grade 1 to Grade 3 in each subtype.The proportion of patients defined as Grade-2 in each subtype were more than 50%,with 1-year transplant free mortalities of 43%,61%and 66%,p=0.070,and in detail Type A was lower than Type C,and Type A was also lower than cirrhotic ACLF which Type B and Type C all included.While,the 28-day and 90-day transplant free mortalities had no differences.The transplant free mortalities of patients defined as Grade-3 in the 3 subtypes were 77%,73%and 75%,p=0.976 in the 28 days,83%,86%and 56%,p=0.981 in the 90 days,and 83%,86%and 92%,p=0.823 in the 1 year.4)The prognosis scores including CTP,MELD,CLIF-C OF and CLIF-C ACLF were comparable between the 3 types at baseline.And both CLIF-C ACLF and COSSH-ACLF scores yielded accurate prognosis for predicting the 28-day,90-day and 1-year prognosis of all the 3 types patients with all AUCs were more than 0.8 for CLIF-C ACLF and were more than 0.76 for CLIF-C OF.The predictive abilities of CLIF-C OF and CLIF-C ACLF were better than MELD score and CTP score with significantly higher AUC in all the 3 subtypes.CONCLUSIONHBV-related ACLF developed from chronic hepatitis B,compensated cirrhosis,and decompensation cirrhosis could be unified as a prognosis homogeneous group with high short-medium mortality,which can be early accurately evaluated by CLIF-C OF and CLIF-C ACLF in all subtypes.