All-Cause and Cause-Specific Mortality in Middle-Aged Individuals with Positive HBsAg: Findings from a Prospective Cohort Study

Abstract

Background: While hepatitis B virus (HBV) is the most prevalent cause of adult liver transplants in Iran, the mortality rates and leading causes of death in HBV patients are not well-understood. This study aimed to investigate all-cause and cause-specific mortality among HBsAg positive individuals in a large Iranian cohort. Methods: The Golestan Cohort Study includes 50045 individuals aged 40–75 residing in Iran’s Golestan province, enrolled during 2004–2008. HBsAg test was performed at baseline. For the present study, individuals with hepatitis C coinfection were excluded. All-cause mortality was considered as the primary outcome. The association between HBsAg and different mortality causes was evaluated using Cox proportional hazard models. P value<0.05 was considered significant. Results: The current study included 49667 participants. After 11.33 (median) follow-up years, there were 7,686 total deaths, with 635 deaths in the HBsAg positive group. In the multivariate Cox proportional hazard model, HBsAg positive individuals had higher all-cause (adjusted hazard ratio [aHR]=1.15, 95% CI: 1.06–1.24) and liver-related mortality risk (aHR=7.13; 5.19–9.79). Mortality from colorectal and pancreatic cancers was higher among male HBsAg positive participants (aHRs=2.41 and 2.22, respectively). Nevertheless, cardiovascular diseases (CVDs) and extrahepatic malignancies were the leading causes of death among both HBsAg positive and negative individuals, and liver-related deaths contributed to an overall 10% of deaths in HBsAg positive patients. Conclusion: HBV is associated with significant mortality risk from different causes in Iranian adults. However, solely focusing on liver outcomes in Iranian HBV patients might result in overlooking non-liver events, especially CVD and extrahepatic cancers.