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Gastroenterology. 2007 Nov;133(5):1452-7. Epub 2007 Aug 2.

Clearance of hepatitis B e antigen in patients with chronic hepatitis B and genotypes A, B, C, D, and F.

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Liver Disease & Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska.



Persistence of hepatitis B e antigen (HBeAg) in chronic hepatitis B has been associated with increased risk for development of cirrhosis and hepatocellular carcinoma. Five hepatitis B virus genotypes were identified in Alaska Native persons; we analyzed clearance of HBeAg by age and genotype.


In this prospective cohort study, 1158 Alaska Native persons throughout Alaska were tested serially for HBeAg for a median of 20.5 years and were genotyped. Initial and final HBeAg-positive specimens, time to clearance, age at clearance, and subsequent HBeAg results were analyzed for persons initially HBeAg-positive. Subsequent HBeAg results were analyzed for persons initially negative.


Genotypes A, B, C, D, and F were identified. Genotype C persons initially HBeAg-positive were more likely than those with other genotypes to be positive on initial and final specimens (P < .001 for each) and time to HBeAg clearance was longer (P < .001). Age at which 50% of persons cleared HBeAg was <20 years for those infected with genotypes A, B, D, and F and 47.8 years in genotype C (P < .001). After losing HBeAg, those with genotypes C and F were more likely to revert to the HBeAg-positive state (P < .001).


Genotype may have a strong effect on mode of transmission and outcome. Genotype C may have been responsible for most perinatal transmission, given that seroconversion from HBeAg occurs decades later than in other genotypes.

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