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Background Limited data are available regarding global hepatitis B virus (HBV)-related morbidity and mortality and potential reduction in disease burden from hepatitis B vaccination.Methods A model was developed to calculate the age-specific risk of acquiring HBV infection, acute hepatitis B (illness and death), and progression to chronic HBV infection. HBV-related deaths among chronically infected persons were determined from HBV-related cirrhosis and hepatocellular carcinoma (HCC) mortality curves, adjusted for background mortality. The effect of hepatitis B vaccination was calculated from vaccine efficacy and vaccination series coverage, with and without administration of the first dose of vaccine within 24 h of birth (i.e. birth dose) to prevent perinatal HBV infection.Results For the year 2000, the model estimated 620?000 persons died worldwide from HBV-related causes: 580?000 (94%) from chronic infection-related cirrhosis and HCC and 40?000 (6%) from acute hepatitis B. In the surviving birth cohort for the year 2000, the model estimated that without vaccination, 64.8 million would become HBV-infected and 1.4 million would die from HBV-related disease. Infections acquired during the perinatal period, in early childhood (<5 years old), and =5 years of age accounted for 21, 48, and 31% of deaths, respectively. Routine infant hepatitis B vaccination, with 90% coverage and the first dose administered at birth would prevent 84% of global HBV-related deaths.Conclusion Globally, most HBV-related deaths result from the chronic sequelae of infection acquired in the perinatal and early childhood periods. Inclusion of hepatitis B vaccine into national infant immunization programs could prevent >80% of HBV-related deaths. [ABSTRACT FROM AUTHOR]