Background: Hepatitis B virus infection (HBV) is a major health problem worldwide. Iran as an intermediate endemicity country has had a decreasing prevalence during the last decade. We aimed to study the epidemiological features of HBV and the spontaneous loss of hepatitis B surface antigen (HBsAg) in HBV infected (HBeAg negative and genotype D) subjects followed-up during 2003 to 2012. Methods: Golestan cohort study (GCS) is a prospective study of 50,049 adults (58% female, age 40-75 years) originally intended to study the upper GI cancers in North Eastern Iran (2004-2008). GCS subjects are74% Turkmen, 80% live in rural areas, 88% are married,83% are non-smokers, and 70% have no formal education. HBV infection (HBeAg negative and genotype D) was found to be the most common cause of end-stage liver disease during GCS follow-ups. Baseline serology for HBV and HCV infection was obtained for all participants and a subcohort of HBV infected subjects were established within the GCS. Repeated measurements of exposure including HBV infection risk factors and a repeated serologic assessment for markers of HBV infection was performed in 2012 after an average of 5 years from enrollment. Results: A total of 3532 subjects from GCS were found to be HBs Ag positive at baseline and were enrolled in Golestan HBV cohort study. After 5 years of follow-up, 2413 subjects were available for reassessment. Of those, 2123 were found to be HBs Ag positive and 290 subjects were HBs Ag negative (12.0%, annual rate: 2%). Among the 290 subjects with spontaneous loss of HBs Ag, 159 (54.8%) were anti-HBc antibody positive and 71 (24.5%, annual rate: 0.5%) subjects developed anti-HBs antibody. During the average of 5.9 years of follow-up (21107 Person years) 35 HBV infected subjects died of end stage liver disease (annual mortality rate: 1.66 per 1000 persons) Conclusions: HBe Ag negative HBV genotype D infected adults in our cohort had 6 year survival rate of 92.8% with 12.0% chance of spontaneous Loss of HBsAg.
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