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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Livingston
Stephen E
SE
Liver Disease & Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska. slivings@anmc.org
Simonetti
Josephine P
JP
Bulkow
Lisa R
LR
Homan
Chriss E
CE
Snowball
Mary M
MM
Cagle
Henry H
HH
Negus
Susan E
SE
McMahon
Brian J
BJ
D000293:Adolescent; D000328:Adult; D000413:Alaska; D006528:Carcinoma, Hepatocellular / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000208:ethnology / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007198:Indians, North American / Q000208:ethnology / Q000235:genetics; D008103:Liver Cirrhosis / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors
D006513:Hepatitis B e Antigens