ABSTRACT
BACKGROUND & AIMS: 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.
Subject(s)
Hepatitis B e Antigens/blood , Hepatitis B virus/genetics , Hepatitis B virus/immunology , Hepatitis B, Chronic/genetics , Hepatitis B, Chronic/immunology , Adolescent , Adult , Alaska , Carcinoma, Hepatocellular/genetics , Cohort Studies , Female , Genetic Predisposition to Disease , Genotype , Hepatitis B, Chronic/ethnology , Humans , Indians, North American/ethnology , Indians, North American/genetics , Liver Cirrhosis/genetics , Liver Neoplasms/genetics , Male , Middle Aged , Prospective Studies , Risk FactorsABSTRACT
BACKGROUND: The highest incidence of hepatitis B virus (HBV)-associated vasculitis in the world has been reported in Alaska Natives. We examined the incidence of HBV-associated vasculitis before and after mass HBV vaccine immunization and the association between HBV genotype and vasculitis in a population-based cohort study in Alaska natives chronically infected with HBV. METHODS: Genotyping was performed in vasculitis cases and 644 hepatitis B-positive controls without vasculitis using polymerase chain reaction and sequencing of the S gene. Occurrence of HBV vasculitis from 1974 to 2004 was calculated. HBV vasculitis patients and controls were also tested for basal core promoter and precore mutations. RESULTS: Fifteen cases of HBV-associated vasculitis were identified: 13 (86%) had genotype D and one each genotype A and F. Genotype D was more commonly found in patients with vasculitis than controls [odd ratio (OR)=5.9, confidence interval (95% CI) 1.2, 21.8; P<0.015). CONCLUSIONS: HBV-associated vasculitis was associated with genotype D.
Subject(s)
DNA, Viral/blood , Hepatitis B virus/genetics , Hepatitis B/complications , Inuit , Vasculitis/etiology , Adolescent , Adult , Aged , Case-Control Studies , Child , Child, Preschool , Female , Genes, Viral , Genotype , Hepatitis B/ethnology , Hepatitis B/virology , Humans , Male , Middle Aged , Mutation , Treatment Outcome , Vasculitis/ethnologyABSTRACT
BACKGROUND: The development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection has been associated with specific HBV genotypes and the presence of specific mutations. METHODS: From a cohort of Alaska Native people with chronic HBV infection, we genotyped 47 patients with HCC and 1129 patients without HCC, and we tested patients with HCC and control patients for mutations in the basal core promoter and precore regions. RESULTS: Genotype F was found in 68% of patients with HCC, versus 18% of those without HCC (P<.001). For patients with genotype F, the median age at diagnosis of HCC was lower than that for patients with other genotypes (22.5 vs. 60 years, respectively; P=.002). Overall, there were no significant differences in the number of basal core promoter and precore region mutations between patients with HCC and control patients. CONCLUSIONS: We found a significant association between genotype F and the development of HCC among Alaska Native people with chronic HBV infection but no significant association between HCC and basal core promoter or precore mutations in genotype F.
