Development Of Diagnostic Criteria And A Prognostic Score For Hepatitis B Virus-related Acute-on-chronic Liver Failure

Background/aim:The definition of ACLF based on cirrhosis,irrespective of cause,is still controversial.The purpose of this study was to clarify the clinicopathological characteristics of patients with hepatitis B-related ACLF(HBV-ACLF)in a prospective,multiple-center study and developed a new diagnostic criteria and prognostic score of HBV-ACLF.Methods:1476 hospitalized Patients with acute decompensation of cirrhosis or with acute severe liver injury(TB[total bilirubin]≥ 5 mg/dL and INR[international normalized ratio]≥1.5)due to chronic hepatitis B(CHB)were initially enrolled from 13 liver centers in China.The clinical characteristics,indicators of prognosis and serum macrophage inflammatory protein 3a(MIP-3a)levels were used to develop a new diagnostic criteria and prognostic score.Results:2638 patients were screened from June 2013 to October 2016.After exclusion,1322 patients were studied:171 had HBV infection with acute severe liver injury(HBV-ASI-NC),1031 had HBV infection with acute decompensation of cirrhosis(HBV-AD-C)and 120 had acute decompensation of cirrhosis caused by Non-HBV pathogens(NonHBV-AD-C).Of the patients assessed using the chronic liver failure(CLIF)consortium criteria,with the exception of cirrhosis,391 patients were identified as having ACLF:92 with HBV-ACLF without cirrhosis(HBV-ACLF-NC),271 with HBV-ACLF with cirrhosis(HBV-ACLF-C)and 28 ACLF with cirrhosis caused by non-HBV pathogens(NonHBV-ACLF-C).The short-term(28/90-day)mortalities of patients with HBV-ACLF-NC and HBV-ACLF-C were significantly higher than the mortalities of patients with NonHBV-ACLF-C.The liver and coagulation were the most frequent site of organ failure.The further analysis revealed in 1119 enrolled patients with an HBV infection(transplant-free)that liver failure alone with an INR>1.5 was proposed as an additional diagnostic indicator of HBV-ACLF.The new diagnostic system effectively identified the high-mortality population,and 19.3%of patients with an HBV infection were also diagnosed with ACLF.The new prognostic score for short-term mortality was superior to the European Association for the Study of the Liver(EASL)score and other scores from both discovery and external validation studies.MIP-3a levels were further shown to exhibit similar serological characteristics between patients with HBV-ACLF-NC and HBV-ACLF-C.ConclusionsRegardless of the presence of cirrhosis,patients with CHB,liver failure alone and an INR ≥1.5 should be diagnosed with ACLF.A new HBV-ACLF definition bridges the gap in the EASL diagnosis of HBV-ACLF,and nearly 20%more patients with an HBV infection who may receive intensive management were also diagnosed with ACLF.