Reversibility of Acute-on-chronic Liver Failure Syndrome in Hepatitis B Virus-infected Patients With and Without Prior Decompensation

Hongmin Wang; Jingjing Tong; Xiang Xu; Jing Chen; Xiuying Mu; Xingran Zhai; Zifeng Liu; Jing Chen; Xiaoyan Liu; Haibin Su; Jinghua Hu


J Viral Hepat. 2022;29(10):890-898. 

In This Article

Abstract and Introduction


Acute-on-chronic liver failure (ACLF) is a severe clinical syndrome associated with high short-term mortality and reversibility. This study aimed to compare the characteristics of survival and reversibility in hepatitis B virus (HBV)-related ACLF (HBV-ACLF) patients with and without previous decompensation. Overall, 1044 patients who fulfilled the acute hepatic insult criteria of the APASL-ACLF Research Consortium (AARC) definition were enrolled from a prospectively established cohort of HBV-related liver failure patients. These patients were divided into the AARC ACLF group and the non-AARC ACLF group according to prior decompensation. Mortality, reversibility of ACLF syndrome, and predicted factors associated with reversibility were evaluated. Liver transplantation-free mortality of the AARC ACLF group was significantly lower than that of the non-AARC ACLF group (28 days: 28.2% vs. 40.3%, p = .012; 90 days: 41.7% vs. 65.4%, p < .001). The 5-year cumulative reversal rates of ACLF syndrome were 88.0% (374/425) and 66.0% (31/47) in the AARC and non-AARC ACLF groups, respectively, (p = .039). Following reversibility of ACLF syndrome, 340/374 (90.9%) and 21/31 (67.7%) patients in the AARC and non-AARC ACLF groups, respectively, maintained a stable status within 5 years. Although prior decompensation indicated poor reversibility of ACLF syndrome, HBV-infected patients with prior decompensation who fulfilled the acute hepatic insult criteria of the AARC definition showed favourable reversibility and maintained a stable status after receiving nucleoside analogues. The AARC ACLF definition identified HBV-ACLF as a distinct syndrome with good reversibility. HBV-infected patients with prior decompensation could be included in the AARC ACLF management.


Acute-on-chronic liver failure (ACLF) is a severe clinical syndrome with high short-term mortality. Although ACLF is a widely known disease, universally accepted diagnostic criteria have not been established.[1] In contrast to the European Association for the Study of the Liver (EASL), the Asia-Pacific Association for the Study of Liver Disease (APASL) defined ACLF as a distinct clinical syndrome of liver failure in a patient with underlying chronic liver disease (CLD) presenting with jaundice, coagulopathy and incidence of complications (i.e. ascites and/or hepatic encephalopathy) developing following hepatic insults and is associated with high short-term mortality.[2] In the APASL-ACLF Research Consortium (AARC) criteria, an acute insult should target the liver, which increases the homogeneity of the ACLF population. Additionally, the underlying CLD of the AARC criteria includes non-cirrhotic CLD and compensated cirrhosis but not decompensated cirrhosis occurs.

Cirrhosis is often asymptomatic until the transition from compensated to decompensated cirrhosis. This transition occurs when cirrhotic complications due to hepatic insufficiency or portal hypertension, including variceal bleeding, ascites, hepatic encephalopathy (HE) and infection, occur.[3–5] However, if cirrhosis is mediated by a treatable cause, patients may recover from a phase with decompensated liver function to compensated liver function.[6] For example, nucleoside analogues (NAs) are widely used in patients with chronic hepatitis B (CHB).[7] Long-term NA therapy, which is used in maintaining a permanent state of virologic suppression, can achieve substantial histological improvement, result in reversal of cirrhosis, and reduce the incidence of liver-specific complications.[8–11]

The AARC criteria define the reversibility of ACLF syndrome as a distinct and important feature of ACLF.[3] Reversibility is manifested as the reversal of key components that define the syndrome of liver failure, namely, a decrease in bilirubin levels, the reversal of coagulopathy and absence of encephalopathy with or without resolution of ascites. The hepatic reserve of decompensated cirrhosis was too poor to achieve reversibility of ACLF syndrome, which was the main reason to exclude it from the underlying CLD of AARC ACLF.[12]

It remains unclear whether the survival and reversibility of hepatitis B virus (HBV)-related decompensated cirrhosis patients are similar to those of patients with AARC ACLF manifesting acute liver failure (jaundice, coagulopathy and incidence of complication, that is, ascites and/or hepatic encephalopathy) following hepatic insults. However, studies on whether patients with decompensated-cirrhotic CHB should be excluded from the ACLF population are still limited.

Therefore, this study aimed to compare the survival and reversibility characteristics of patients with HBV-related ACLF (HBV-ACLF) with and without prior decompensation. The predictors of the reversibility of ACLF syndrome were also investigated.