Classification of Hepatitis B Virus Genotype B into 2 Major Types Based on Characterization of a Novel Subgenotype in Arctic Indigenous Populations

Abstract

Hepatitis B virus genotype B (HBV/B) has been classified into 5 subgenotypes. Except for Bj/B1 in Japan, the subgenotypes (Ba/B2-B5) have undergone recombination with HBV/C in the core promoter/precore/core genomic region. Phylogenetic analyses of complete sequences show that the Arctic strains belong to a novel subgenotype (HBV/B6) without the recombination, analogous to what is seen with Bj/B1. Comparison of 50 HBV/B6 carriers from the Arctic versus 50 Bj and 50 Ba age- and sex-matched carriers from Asia revealed that clinical characteristics of HBV/B6 carriers were similar to those of Bj/B1 carriers in Japan. The results suggest that HBV/B may be classified into nonrecombinant (Bj/B1 and B6) and recombinant (Ba/B2-B5) types.

Clearance of hepatitis B surface antigen and risk of hepatocellular carcinoma in a cohort chronically infected with hepatitis B virus

“…5 One previous case-control study found that persons infected with genotype B had a significantly higher rate of HBsAg clearance than those infected with genotype C. 19 However, based on the geographic distribution of HBV genotypes, genotype B in this study was likely to be B Asia (B2-5), whereas the genotype B found in Alaska Native carriers is a new subtype (B6) that is more closely related to B Japan (B1). 21 Persons who cleared HBsAg have been tested for HBV DNA in three studies. Presence of HBV DNA varied widely and was found in 1.3% and 1.7% at 12 months, 17,22 1.1% at 49 months, 23 and 21.4% at 5 years and 14.3% at 10 years after clearance.…”

Serological and molecular epidemiological outcomes after two decades of universal infant hepatitis B virus (HBV) vaccination in Nunavut, Canada

“…However, even with a high endemic rate of HBV infection, incidence of HCC and cirrhosis were not substantially different from Denmark [73][74], which is not considered endemic due to an HBsAg prevalence of 0.1% [75]. Genotype D and B5 are predominant in Greenland, and a high incidence of B5 infection may explain the relatively low occurrence of HCC and cirrhosis [76][77].…”

“…HBV/B1, the most phylogenetically similar subgenotype to HBV/B5, had 8% of patients progress to end-stage liver disease, while HBV/B2, a 'recombinant' genotype B, had 28% of patients progress to end-stage liver disease [76].…”

“…HBV/B1 and HBV/B5 can therefore be thought of as 'pure' genotype B, a non-recombinant group, while subgenotype HBV/B2-B4 are a recombinant group, clustering closer with genotype C [76]. It has also been shown that subgenotypes HBV/B2-B4 contain genomic sequence corresponding to HBV/C, which includes the core promoter, precore, and core regions [79].…”

“…Because the basal core promoter mutations are generally associated with HBV/C, it could be hypothesized that genotypes B2-B4, containing HBV/C basal core promoter sequence, may lead to increased end-stage liver disease compared to non-recombinant HBV/B. Additionally, the majority of genotype B5 isolates contain the precore G1896A mutation, which is associated with a lowerrisk of HCC compared to wild-type G1896 [76,[80][81]. Understanding these two separate mutation events could explain the lack of HCC and cirrhosis seen in Greenland's, Nunavut's, and Alaska's indigenous populations, where prevalence and genotype distribution for B5 are relatively high.…”