Hepatitis B virus (HBV) genotypes E to J are understudied genotypes. Genotype E is found almost exclusively in West Africa. Genotypes F and H are found in America and are rare in other parts of the world. The distribution of genotype G is not completely known. Genotypes I and J are found in Asia and probably result from recombination events with other genotypes. The number of reported sequences for HBV genotypes E to J is small compared to other genotypes, which could impact phylogenetic and pairwise distance analyses. Genotype F is the most divergent of the HBV genotypes and is subdivided into six subgenotypes F1 to F6. Genotype E may be a recent genotype circulating almost exclusively in sub-Saharan Africa. Genotype J is a putative genotype originating from a single Japanese patient. The paucity of data from sub-Saharan Africa and Latin America is due to the under-representation of these regions in clinical and research cohorts. The purpose of this review is to highlight the need for further research on HBV genotypes E to J, which appear to be overlooked genotypes.

Hepatitis B virus (HBV) classification comprises up to 10 genotypes with specific geographical distribution worldwide, further subdivided into 40 subgenotypes, which have different impacts on liver disease outcome. Though extensively studied, the classification of subgenotype A sequences remains ambiguous. This study aimed to characterize HBV isolates from West African patients and propose a more advanced classification of subgenotype A. Fourteen HBV full-length genome sequences isolated from patients from The Gambia and Senegal were obtained and phylogenetically analyzed. Phylogenetic analysis of HBV genotype A sequences isolated from Senegalese and Gambian patients exhibited separate clusters from the other known and confirmed subgenotypes A (A1, A2, A6). Most of the sequences (10/14) clustered with an isolate from Cuba, reported as subgenotype A4 (supported by maximal bootstrap value). Four isolates from The Gambia and Senegal clustered separately from all other subgenotypes and samples sequenced in the study. Three of which from The Gambia, designated as an expanding clade of subgenotype A4, exhibited a mean inter-subgenotypic nucleotide divergence over the entire genome sequence higher than 4% in comparison with the other subgenotypes and the other isolates sequenced in the study, except with subgenotype A4 isolates (3.9%), and this was supported by a maximal bootstrap value. The last one from Senegal seemed to be an expanding subgenotype close to the new clade of A4. Amino acid analysis unveiled a novel motif specific to these isolates. This study revealed an expanding evolution of HBV subgenotype A and novel amino acid motifs. It also highlighted the need for a consensus regarding the analysis and classification of HBV sequences.