Genetic diversity of hepatitis B virus genotypes B6, D and F among circumpolar indigenous individuals.

Hepatitis B virus (HBV) infection is highly prevalent in circumpolar indigenous peoples. However, the clinical outcome is extremely variable, such that while hepatocellular carcinoma (HCC) is uncommon in Canadian Inuit, the incidence of HCC is slightly higher in Greenlanders than in Danes, and it is especially high in Alaskan Native people infected with HBV genotypes F (HBV/F) and C (HBV/C). These differences may be associated with the genomic variability of the predominant HBV genotype in each group. The purpose of this study was to determine the rate, nature and regional susceptibility of HBV genomic mutations among circumpolar indigenous individuals. Paired serum samples, separated by 5-6 years, were analysed from Canadian and Greenlandic Inuit infected with HBV genotype B6 (HBV/B6) and HBV/D, respectively, and from Alaskan Native people infected with HBV/F, each having subsequently developed HCC. Phylogenetic and mutational analyses were performed on full-genome sequences, and the dynamic evolution within the quasispecies population of each patient group was determined by clonal analysis of the non-overlapping core coding region. Mutations associated with severe outcomes predominated in HBV/F, mostly within the precore/core and PreS1 region. HBV/B6 genomes exhibited higher diversity compared to HBV/D and HBV/F, particularly within the core coding region. Thus, differing mutational profiles and genetic variability were observed among different HBV genotypes predominating in circumpolar indigenous patients. The unusual observation of persistently high genetic variability with HBV/B6 despite clinical inactivity could be due to the evolution of a host-pathogen balance, but other possible factors also need to be explored.

The prevalence and long term outcome of occult hepatitis B virus infections in community based populations.

Features of occult hepatitis B infection in community-based populations have yet to be described. In this study we documented: (1) the prevalence and demographics, (2) associated serology and viral loads, and (3) clinical outcomes of occult hepatitis B infection in community-based populations. Hepatitis B surface antigen (HBsAg)-negative sera collected from three Northern Canadian communities (HBsAg prevalences: 11-12%) in 1983-1985 were tested for HBV-DNA by nested stage polymerase chain reaction. Of 706 HBsAg negative sera, 9 (1.3%) were HBV-DNA positive. The median age of occult hepatitis B infected patients at the time of sampling was 9.8 years (range 3.1-50.4 years) and six (67%) were female. Two (22%) individuals were anti-HBs positive (in the absence of prior vaccination). Viral loads were undetectable in all but two samples (2.40 and 2.86 log10 IU/ml). Only one of the five (20%) patients who were assessed clinically, remained HBV-DNA positive at 25-30 year follow-up. There was no clinical, biochemical or radiologic evidence of chronic hepatitis, cirrhosis or hepatocellular carcinoma in these individuals or on review of the charts from the remaining four infected patients. The results of this study suggest that in community-based populations: (1) occult hepatitis B infection is not as common as HBsAg positive infection, (2) the majority of infected subjects are young females, (3) a minority are anti-HBs positive, (4) viral loads are either undetectable or low, and (5) in the absence of concurrent liver disease, occult hepatitis B infection does not appear to be associated with long term adverse clinical outcomes.