Hepatitis B Virus Genotypes: CliniCal impliCations

425 IntroductIon Hepatitis B virus (HBV) infection is a global health problem. Approximately 400 million people in the world are chronic HBV carries.1 In India, 10% (40 million) of the total carrier population resides.2 Liver injury in HBV infection is predominantly immune-mediated and therefore virus-host interaction is the major determinant of HBV-induced liver disease.3 Host immune system varies from individual to individual and is dependent on many factors, such as, age of infection, genetic susceptibility, inherent immunological competence and environmental factors.4 The virus characteristics may also vary and therefore events determined by host-virus interaction may be extremely heterogeneous causing heterogeneous disease characteristics. HBV is the smallest DNA virus with 3200 base pairs, which contains four overlapping genes (Open Reading Frames or ORFs) encoding the viral envelope (S and pre S), necleocapsid (Precore and Core), polymerase with reverse transcriptase enzyme and X proteins.1 HBV is also known to replicate through RNA intermediates on which reverse-transcriptase enzyme acts to produce complementary DNA (c-DNA) for further replication through DNA-polymerase enzyme.1 Reverse transcriptase is a poor proofreader and therefore nuclear substitution during HBV replication is a spontaneous event. Approximately 1.4 – 3.2 x 10-5 nucleotide substitution per year occurs in the HBV genome during its replication.5 Due to such substitutions the antigenic characteristics of HBV peptides (predominantly documented in the envelope region) may change. Therefore, after a long time of evolution four major HBV serotypes (adw, adr, ayw, ayr) with subtypes have been described.3-4 The major group specific antigen ‘a’ remains similar in all the serotypes, however, the minor variation in the amino acid profile of envelope protein leading to different serotypes of the virus have been associated with epidemiological or distribution characteristics of the virus. Such change in the envelope peptides has been associated with nucleotide changes in HBV genome. Sequence analysis of full length HBV genome of different isolates by now have revealed at least eight different HBV isolates which has variation from each other in more than 8% of genomic sequences.6 These isolates with > 8% variation in nucleotide sequence homology are called ‘HBV genotypes’ and have been alphabetically named from ‘A’ through ‘H’. The relationship between serotypes and genotypes has been elucidated.6 The serotype ayw occurs in all genotypes except in ‘C’. Serotype adw have been associated with all genotype except ‘D’ and ‘E’. Where as adr and ayr subtypes are encountered with genotype ‘C’.