Subgenotypes of hepatitis B virus genotype D (D1, D2, D3 and D5) in India: differential pattern of mutations, liver injury and occult HBV infection

Hepatitis B genotype D (HBV/D) is the most wide-spreadgenotypeandexistsasatleastfivesubgenotypes(HBV/D1–D5). However, little is known about the association ofvirological characteristics with clinical differences amongHBV/D subgenotypes. To investigate the virological charac-teristics of these subgenotypes and their clinical implications,we selected a cohort of 109 genotype D infected individualsfrom the state of West Bengal, India, including 68 HBsAgpositivepatientsand41withoccultHBVinfection.AmongtheHBsAg positive subjects 28 had chronic hepatitis B virusinfection, 40 were asymptomatic carriers based on clinicalexamination, liver function test and ultrasonograph results.Overall,HBV/D1wasfoundin17%,HBV/D2in29%,HBV/D3in 34% and HBV/D5 in 20% of the cases. HBV/D1 wassignificantly associated with chronic liver disease (P = 0.01),and in this subgenotype A1896 (PreC mutations) were mostcommon. Although BCP mutations (A/C1753 and T1762/A1764) were found to be frequently associated with HBV/D2(33% and 33%) and D5 (47% and 59%), no apparent clinicalcorrelation was observed. On the other hand, occult HBVinfection was significantly associated with HBV/D3 infection,along with low level of BCP and PreC mutations and severalnon-synonymous substitutions in the catalytic reversetranscriptase (RT) domain of polymerase gene. Similarnucleotide substitutions in the surface (S) gene region wereobserved from both northern and eastern Indian HBV/D3isolates. In conclusion, HBV/D subgenotypes differ in theirmutational patterns in the S, polymerase and the BCP/PreCregions that may influence their clinical outcomes.Keywords: genetic diversity, genotypes and subgenotypes,HBV mutations, hepatitis B virus, RT domain.