Causes of death in patients with hepatitis B: a natural history cohort study in the United States.

The natural history of hepatitis B virus (HBV) infection in a U.S. population has not been well described. We identified the causes of death in 6,689 health plan members infected with HBV who were followed between March 1, 1996 and December 31, 2005. Causes of death were grouped into HBV-related (subdivided into decompensated cirrhosis [DCC] and hepatocellular carcinoma [HCC]), cancer, cardiovascular, and other/unknown. The study cohort included 3,244 females and 3,445 males; 68.3% were of Asian-Pacific Islander (API) descent, 11.8% were white (non-Hispanic), and 19.9% were of other or unknown race. Exposure to HBV antivirals and preexisting comorbidities were uncommon. Males had higher overall 10-year death rates than females, both for total deaths (8.9% versus 4.1%) and for HBV-related deaths (4.8% versus 1.2%). The death rate rose markedly with increasing age, and approximately 40% of all deaths in subjects over the age of 40 were HBV related. The death rate from HCC was twice that of DCC. HCC deaths represented 70% of cancer deaths in males and 37% in females. On multivariable analysis, when subjects with antecedent HCC and DCC were excluded, the only significant predictor of HBV mortality in both sexes was age. HBV was the cause of death in over 40% of those who died during the study, and the mortality increased markedly with increasing age over 40 in males and over 50 in females. HBV-related mortality was four times more common in males than in females and was as common in non-Asians as in those of API origin. HBV-related deaths were twice as common from HCC as from DCC.