Molecular epidemiology and genetic characterization of hepatitis B virus in the Indian subcontinent.

Summary Background Hepatitis B virus (HBV) is a gradually evolving virus. The aim of this study was to characterize the distribution pattern of HBV genotypes and subgenotypes and HBsAg subtypes in chronic hepatitis B subjects from the Indian subcontinent. We also sought to investigate the genetic diversity of HBV genotypes and its influence on the therapeutic response. Methods A total of 295 chronic hepatitis B subjects were studied. HBV genotypes and subgenotypes were determined using the generated HBV reverse transcriptase (rt) sequences. HBsAg subtypes were predicted using a newly developed automated program in Microsoft Visual Basic (VB6). Genetic diversity was characterized by calculating the mean genetic distance ( d ), the number of synonymous substitutions per synonymous site ( d S), and the number of non-synonymous substitutions per non-synonymous site ( d N). The virological response was measured by HBV DNA levels. Results In southern India, the predominant HBV subgenotype/subtype was D2/ ayw3 (79.1%). In eastern India, C1/ adr (28.2%) was found to be the predominant subgenotype/subtype, followed by A1/ adw2 (25.4%). In the north-eastern region, C2/ adr , D2/ ayw3 , and D5/ ayw3 were predominant and were each identified in 20.8% of subjects. In treatment-naive subjects, the d , d S, and d N of genotype D sequences were higher compared to genotypes C and A. Additionally, the d , d S, and d N of HBV rt sequence were higher in subjects who subsequently showed a virological response to nucleos(t)ide analogues as compared to non-responders, irrespective of the genotypes tested ( p =0.014 to p Conclusions We have described the distribution of HBV genotypes and subgenotypes and HBsAg subtypes in three major regions of the Indian subcontinent. HBV genetic diversity may play a pivotal role in the clinical outcome of chronic hepatitis B.