The relationship between stages of chronic hepatitis B liver disease and health-related quality of life (HRQoL) is an important aspect of the overall management of hepatitis B virus (HBV) infection, yet is not well characterized. Consequently we sought to examine HRQoL in HBV patients, stratified by disease severity, compared with normal controls and hypertensive patients, using the Short Form 36 Health Survey (SF-36) and the EQ-5D self-report questionnaire. Univariate and multivariate analyses were then performed. A total of 432 HBV (156 asymptomatic carriers, 142 chronic hepatitis B, 66 compensated cirrhosis, 24 decompensated cirrhosis, 22 hepatocellular carcinoma, and 22 post-liver transplant) patients, 93 hypertensive patients, and 108 normal controls participated in the study. Multivariate analysis showed that normal controls and asymptomatic carriers had similar SF-36 scores, which were better than those for hypertensive patients, but with development of chronic hepatitis B and compensated cirrhosis, showed a significant decrease in general health and the mental dimension, whereas those with advanced liver disease (decompensated cirrhosis and hepatocellular carcinoma) had significantly lower scores in all components (P < 0.05), indicating that the physical component deteriorates only with advanced liver disease. Similar results were obtained with EQ5D. Post-liver transplant patients had similar HRQoL to patients with decompensated cirrhosis and hepatocellular carcinoma, although there was a trend toward improvement. Chronic hepatitis B infects approximately 400 million people worldwide and causes 1 million deaths annually of liver disease. 1 Clinically, people with chronic hepatitis infection are at high risk of liver damage, with approximately 15% to 40% of infected patients eventually developing cirrhosis, liver failure, or hepatocellular carcinoma during the course of hepatitis B virus (HBV) infection. 2 HBV is the leading worldwide cause of liver disease, liver death, and liver morbidity. 3 In the United States, 4 although the prevalence of chronic HBV infection is low (prevalence of 0.48% in the prevaccination era 5 ), approximately 1.2 million people are infected, particularly in high-risk populations such as Alaskan natives, Pacific Islanders, and first-generation immigrants from high endemic areas, intravenous drug users, men who have sex with men, healthcare workers, and immunosuppressed and renal dialysis patients. Symptoms of acute HBV are well documented; however, those of chronic HBV infection are less clear. Little is known about symptoms in patients with chronic hepatitis B and even less about its impact on the health-related quality of life (HRQoL) of such patients; consequently, it is a field that is poorly studied despite this being the most prevalent form of chronic viral hepatitis worldwide. In contrast, HRQoL has Abbreviations: EQ5D, EQ-5D self-report questionnaire; HBV, hepatitis B virus; HRQoL, MCS, mental component summary; PCS, physical component summary; 36 Health Survey; VAS, vi...