Objectives: Patients with acute-on-chronic liver failure (ACLF) experience long-term chronic liver diseases plus an acute liver function decompensation. This study aimed to determine whether psychological symptoms in patients with hepatitis B virus (HBV)-related ACLF differ from those with other chronic liver diseases and to identify which factors could predict psychological impairment in liver patients. Methods: This was a paired case control study. A total of 120 inpatients, including 40 cases for HBV-related ACLF, 40 paired controls for HBV-related cirrhosis and 40 paired controls for chronic hepatitis B (CHB), as well as 40 paired healthy controls were studied. Results: A high proportion of patients with HBV-related ACLF were classified as Child's stage C. The prevalence of depression in patients with HBV-related ACLF was significantly higher than in CHB patients and healthy controls, but was equivalent to patients with HBV-related cirrhosis. Patients with HBV-related ACLF had significantly higher level of self-esteem than those with HBV-related cirrhosis. However, there was no significant difference among the three liver patient groups and healthy controls in anxiety and suicide intent. Lower education level, anxiety, poor sleep quality and greater severity of disease were associated with elevated depression. Conclusions: Patients with HBV-related ACLF and cirrhosis are at higher risk of depression. It appears that severity of liver disease measured by Child-Pugh class, rather than additional acute liver function decompensation, significantly predicted depression among liver patients. (C) 2012 Elsevier Inc. All rights reserved.