Chronic hepatitis B (CHB) is considered the most prevalent cause of cirrhosis in Iran; however, mortality rate and top death causes of CHB patients are not well-clarified. Therefore, this study aimed to investigate all-cause and cause-specific mortality among CHB patients of a large population-based Iranian cohort.

Golestan Cohort Study population consisted of 50,045 individuals aged 50-75 years, who were recruited during 2004-2008 and followed annually ever since. The latest followup update was performed in February 2019. In the current study, CHB was defined as having positive HBsAg at baseline, while all-cause mortality was considered as the primary outcome. Mortality rates were evaluated using Cox proportional hazard regression models. Population Attributable Fraction was calculated for estimating the contribution of CHB to all-cause and cause-specific mortalities in total population.

Overall, there were 7354 deaths during a median followup of 12 years, with 613 deaths in CHB patients. The top five causes of death were similar among HBsAg positive (CHB) and negative (healthy) individuals; however, liver cancer deaths and non-cancer liver deaths were more prevalent among CHB patients. In the univariate cox proportional hazard model, CHB patients had a significantly higher all-cause (adjusted Hazard ratio=1.23, 95% CI: 1.13-1.33) and liver-related morality (aHR=6.43; 4.62-8.86) compared to healthy individuals. The full-adjusted model indicated significantly higher risk of liver cancer (aHR=15.35; 8.11-29.05) mortality among male CHB patients, but not in female counterparts (p for interaction= 0.006). The risk of non-liver non-cancer mortalities were similar in both groups. Approximately, 27.3% of the overall liver mortality was attributed to the effect of CHB in the cohort population.

CHB is associated with a significant preventable risk of mortality in both genders. These findings signify the importance of diligent followup in HBsAg positive individuals, particularly male patients.