Classifying Hepatitis B Virus Genotypes

In 1988, hepatitis B virus (HBV) was classified into four genotypes by a sequence divergence in the entire genome exceeding 8%, and designated by capital letters of the alphabet from A to D. There are seven genotypes of HBV (A–G) at present, and an eighth is on the horizon. They have an uneven geographical distribution, and only a few of them are prevalent in a given area of the world. Thus genotype A is frequent in northwest Europe, Sub-Saharan Africa, India and the North, Central and South America, B as well as C are common in Southeast Asia and Oceania, and D is prevalent in the Mediterranean area, Central Asia and South America. Genotype E is restricted to West Africa, and F is localized in Central and South America. The distribution of genotype G added to the alphabet list very recently has yet to be determined. Coinfection with HBV of distinct genotypes is not infrequent and found in about 10% of infected individuals, and is responsible for intertypic recombination of HBV genomes. The mutation for a stop codon in the precore region (G1896A) for aborting the translation of hepatitis B e antigen (HBeAg) is prohibited in HBV genomes of genotype A, as well as some of genotypes C and F, because they possess C at position 1858 that makes a Watson-Crick pair with G at position 1896. Hence, seroconversion to antibody to HBeAg is forbidden or delayed in individuals who carry them. Evidence is accumulating as regards the influence of HBV genotypes on the progression of chronic hepatitis B and response to antiviral therapies. HBV isolates even of the same genotype can differ in virological and clinical characteristics, and therefore, the genotype needs to be classified further into subtypes, especially if they are clinically relevant.