Abstract
Hepatitis B virus (HBV) is one of the major global public health problems. In India, HBsAg prevalence among general population ranges from 2% to 8%, placing India in intermediate HBV endemicity zone and the number of HBV carriers is estimated to be 50 million, forming the second largest global pool of chronic HBV infections. India is a vast country, comprised of multiracial communities with wide variations in ethnicity and cultural patterns, which is attributable to its geographical location, gene influx due to invasion and/or anthropological migrations in the past. Moreover, recent increase in trade, trafficking and use of illicit drugs has also considerably influenced the epidemiology of HBV, specifically in the eastern and north eastern parts of India. However, data on the molecular epidemiology of HBV in India is scanty. HBV genotypes A and D have been well documented from different parts of mainland India. Interestingly, in addition to genotypes A and D, genotype C having high nucleotide similarity with south East Asian subgenotype Cs/C1 strain, have been detected exclusively from eastern Indian HBV carriers, suggesting a recent introduction. Thus, compared to other parts of India, the molecular epidemiology of HBV is naturally distinct in eastern India. Very recently, taking the advantage of circulation of three distinct HBV genotypes within the population of eastern India, different aspects of HBV molecular epidemiology was studied that revealed very interesting results. In this study, the clinical significance of HBV genotypes, core promoter and precore mutations, possible routes of introduction of HBV genotype C in eastern India, the clinical implications of x gene variability, prevalence of the AFB1 induced p53 gene codon 249 mutation, the transmission potentiality of HBV among asymptomatic/inactive or occult HBV carriers and the genetic variability of HBV persisting in the PBL was investigated. In this manuscript, the information available on the molecular epidemiology of HBV in India has been reviewed and the results of studies among the eastern Indian population have been summarised.
Highlights
Hepatitis B virus (HBV) is one of the major global public health problems
Based on the prevalence of HBV surface antigen (HBsAg) carrier rate in the general population, sub-Saharan African, East Asian and Alaskan populations are classified as having high HBV endemicity (HBsAg carriage > 8%), while the populations of southern parts of Eastern and Central Europe, the Amazon basin, the Middle East, and the Indian subcontinent are classified as intermediate HBV endemicity (HBsAg carriage 2–7%), and the populations in western and northern Europe, North America, and Australia are classified as low HBV endemic (HBsAg carriage < 2%) regions [2]
The results of this thesis sheds light on many important aspects of HBV molecular epidemiology that are very much important for identifying the population at risk of acquiring HBV and developing severe disease, and pose a risk of transmission through different modes. This information are essential for determining the risk factors associated with HBV infections, to formulate necessary preventive measures to lessen the burden of new infections and spread of newly introduced genotype to other parts, from eastern India
Summary
Hepatitis B virus (HBV) is one of the major global public health problems. HBV infection is the 10th leading cause of death and HBV related hepatocellular carcinoma (HCC) is the 5th most frequent cancer worldwide. Taking the advantage of the distribution of three distinct HBV genotypes within the same population of eastern India the thesis work was aimed to (i) study the molecular epidemiology and clinical significance of hepatitis B virus genotypes, core promoter and precore mutations in eastern India, (ii) identify possible routes of introduction of HBV genotype C in Eastern India, (iii) analyze the HBV x gene variability and its implications in Eastern Indian HBV carriers, (iv) determine the prevalence of the specific mutation of p53 gene (at codon 249), (v) study the transmission potentiality of HBV among family members of asymptomatic/inactive HBV carriers and (vi) study the genetic variability of HBV isolates persisting in the PBL. During this work, detailed comparison and analysis of the pregenomic RNA base pairing of different HBV genotypes suggested a potential molecular mechanism that explained the specific selection of the G145R mutation in the context of subgenotype Ae/A2 specific sequences and higher immune selection on the PBL [Datta et al Manuscript under review]
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