Long-term Outcomes of Patients With Hepatitis B Virus-related Acute on Chronic Liver Failure

An Observational Cohort Study

Su Lin; Kai Zhang; Junchao Zhang; Mingfang Wang; Bharat Velani; Yueyong Zhu


Liver International. 2019;39(5):854-860. 

In This Article

Abstract and Introduction


Background and Aims: The long-term outcomes of patients with hepatitis B virus-related acute on chronic liver failure (HBV-ACLF) remain unclear. The main aim of the study was to compare the 5-year survival rate and incidence rate of hepatocellular carcinoma (HCC) between patients with HBV-ACLF and HBV-cirrhosis.

Methods: Clinical data of patients with ACLF, compensated cirrhosis and decompensated cirrhosis who survived more than 3 months after diagnosis were collected. The survival rate and cumulative incidence of HCC were compared. The Cox regression was used to evaluate risk factors for outcomes.

Results: A total of 814 patients were included in the analysis, including 122 (14.99%) patients with ACLF, 450 (55.28%) patients with compensated cirrhosis and 242 (29.73%) patients with decompensated cirrhosis. The 5-year survival rate of patients with ACLF (97.2%) was higher than patients with decompensated cirrhosis (86.0%), but was lower than patients with compensated cirrhosis (99.1%). The 5-year HCC incidence rate was the highest in the decompensated cirrhosis group (14.6%, P < 0.05), while no statistical differences were found between patients with ACLF (3.5%) and compensated cirrhosis (9.5%). The episode of ACLF did not increase the risk of HCC and the overall survival when compared with patients with cirrhosis. In ACLF subgroup analysis, the age, rather than the presence of cirrhosis, was independently associated with both mortality and incidence of HCC.

Conclusions: ACLF patients who survived the first 3 months had a better long-term prognosis than decompensated cirrhosis, while the HCC risk was comparable to compensated cirrhosis. HCC surveillance is strongly recommended for these patients.


Hepatitis B virus (HBV) is a major health problem with an estimated of 350 million infection globally. Chronic hepatitis B leads to various hepatic complications, such as cirrhosis, liver failure and hepatocellular carcinoma (HCC).[1] Acute on chronic liver failure (ACLF) is an unique presentation of chronic hepatitis B. It is defined as an acute hepatic insult in a patient with previously diagnosed or undiagnosed chronic liver disease or cirrhosis, leading to jaundice and coagulopathy complicated by clinical ascites and/or encephalopathy.[4,5] ACLF has a high short-term mortality with a spontaneous recovery rate under 50%.[6] For those who can survive through this acute insult, there remains a higher activation of hepatic stellate cells and consequently the proliferation of fibrous tissue in the liver. Without intervention, more than 80% of the survivors will progress to post-necrotic cirrhosis in the following years.[7]

The long-term outcome of liver failure has not been thoroughly investigated though. Patients with Wilson's disease who presented with ACLF had a much worse prognosis than those presented with acute liver failure.[8] Recently, Yoon et al[9] found that ACLF episode alone was not an independent factor for long-term survival in patients with ACLF who survived over the first 3 months, while prior history of acute decompensation (AD) is a more important factor affecting long-term outcomes. However, little is known about the long-term prognosis of HBV-related ACLF (HBV-ACLF) patients, especially when compared with HBV-related cirrhosis. Moreover, it remains unknown whether or not the risk of HCC increases in HBV-ACLF patients when compared to cirrhotic patients without an episode of acute insult. Therefore, the purpose of this study was to compare the long-term outcomes, including the survival rate and the incidence of HCC, between patient groups of HBV-ACLF and HBV-related cirrhosis, and to investigate the risk of HCC in ACLF patient group.