Risk and Predictors of Mortality Associated With Chronic Hepatitis B Infection

Background & Aims: The study objective was to determine the risk of all-cause and cause-specific mortality as well as to examine the predictors of mortality in chronic hepatitis B infection. Methods: We performed a prospective cohort study of 23,820 persons (age, 30-65 y) recruited between 1991 and 1992 and followed up through 2004 from 7 townships in Taiwan. The main outcomes were all-cause and liver-related mortality rates. Mortality analyses used time-to-events methods, and survival curves were derived by the Kaplan-Meier method. Cox proportional hazard models were used to estimate multivariable-adjusted hazard ratios. Results: There were 1814 deaths during a mean follow-up period of 12.5 years (282,323.7 person-years of follow-up evaluation). Persons positive for hepatitis B surface antigen (HBsAg) had significantly (P < .01) higher adjusted hazard ratios for all causes of mortality (1.7; 95% confidence interval [CI], 1.5-1.9), liver cancer mortality (22.4; 95% CI, 15.2-32.9), and chronic liver disease and cirrhosis mortality (5.4; 95% CI, 3.5-8.4). When compared with HBsAg-negative persons, hepatitis B virus (HBV)-infected persons with HBV DNA levels less than 104 had a high risk of hepatocellular carcinoma mortality (4.4; 95% CI, 2.4-8.2). In HBsAg-positive persons, the mortality rate increased with cohort entry serum HBV DNA level. Liver cancer mortality ranged from 72.8 per 100,000 person-years for subjects with HBV DNA levels less than 300 copies/mL to 815.6 per 100,000 person-years for those with HBV DNA levels of 1 million copies/mL or greater. Chronic liver disease and cirrhosis deaths ranged from 9.1 to 267.4 per 100,000 person-years. Conclusions: Chronic HBV infection is associated with significant preventable excess mortality risk. This mortality risk is correlated strongly with the level of viral replication among other factors.