The association between hepatitis B virus longitudinal genetic variability and clinical outcome in circumpolar indigenous populations
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The true prevalence of hepatitis B virus (HBV) infections in Northern Canada is underreported owing to the lack of occult-HBV studies. Clinical outcomes of HBV infections are variable; such that active disease is rare in Canadian and Greenlandic Inuit, yet hepatocellular carcinoma (HCC) is prevalent among genotype F (HBV/F) infected Alaskan Natives. The purpose of this study is to determine the true extent of occult infections in Northern Canada and the rate, nature and regional susceptibility of HBV genomic mutations among circumpolar indigenous populations. The occurrence of occult infections in 700 archived serum samples from Northern Canada was determined by viral DNA amplification. In addition, HBV mutational analysis was performed on 15 indigenous peoples infected by one of 3 HBV genotypes (B6, D and F), which are associated with varying outcomes, including inactive liver disease and HCC. Phylogenetic analyses and genetic variation was investigated with full-length HBV genomes. The results show 3.8% of 700 study subjects to be occult-HBV positive, with half of them infected with HBV/A. This study also reveals HBV/F strains contain deletions and substitutions associated with adverse outcomes, while HBV/D and B6 sequences lacked these mutations and contained mutational patterns associated with a benign outcome. The genetic diversity within the dominant and subclonal population levels are higher for HBV/B6 strains compared to HBV/D and HBV/F strains. The increased genetic variability found in virus associated with inactive disease may be indicative of an escape mechanism used by HBV to evade the host immune response or simply co-evolution between the virus and its host. These observations may demonstrate the association between differing clinical outcomes and infecting genotype in circumpolar indigenous populations.