Abstract
Hepatitis B Virus (HBV) manifests high genetic variability and is classifiable into ten genotypes (A-J). HBV infection can lead to variable clinical outcomes, ranging from self-limiting acute hepatitis to active chronic hepatitis, cirrhosis and hepatocellular carcinoma. The present study characterizes HBV strains circulating among patients with acute (AHB) and chronic HBV infection (CHB). Among a total of 653 HBsAg positive cases, 40 manifested acute infection. After sequencing the surface(S), basal core promoter/pre-core(BCP/PC) and the X gene regions, phylogenetic tree was constructed using MEGA4 by neighbor-joining method. Statistical robustness was established with bootstrap analysis. Nucleotide diversity was determined by Shannon entropy per site using the Entropy program of the Los Alamos National Laboratories. Analyses of acute patients revealed that HBV/D2 is the major circulating sub-genotype and commonly associated with sexual promiscuity and the age group between15-30 years. Comparison of AHB and CHB patients revealed that HBeAg positivity, ALT levels and genotype D were significantly high in AHB, whereas CHB patients were predominantly male, had a high viral load, and were commonly associated with genotype C. The frequencies of mutations in the S, BCP/PC, and X gene were low in AHB as compared to CHB. Drug resistant mutations were not detectable in the polymerase gene of AHB. Average nucleotide diversity in AHB was considerably low as compared to CHB. Further, the highest average ΔH (average difference in entropy between chronic and acute infection) was observed in the BCP/PC region implying that this region was most vulnerable to mutations upon HBV persistence, especially in case of genotype C. Additionally, among all substitutions, the A1762T and G1764A BCP mutations were the strongest indicators of chronicity. In conclusion, the study exhibits a general portrait of HBV strains circulating among acute hepatitis B patients in Eastern India and their intricate differences with chronic patients which should be useful from the clinical point of view.
Highlights
Hepatitis B virus (HBV) is a global health threat affecting about 350 million people across the world [1]
Further analysis of genotypes and its association with the modes of transmission revealed that HBV/D2 was the most prevalent subgenotype which was highly associated with sexual promiscuity (Fig 1C) and notably HBV/D2 was predominantly associated with the age group of 15 to 30 years (Fig 1D)
The current study presents a comprehensive picture of HBV strains circulating among acute Hepatitis patients in Eastern India
Summary
Hepatitis B virus (HBV) is a global health threat affecting about 350 million people across the world [1]. Studies on acute HBV infection are significant since it informs us about newly emerging viral strains [3] apart from shedding light on the prominent modes by which adult infection is transmitted [4]. It highlights the mutations in the HBV genome which are transmissible and provide extremely important information in the attempts to contain HBV spread [5]. An early study on acute patients in Japan revealed that genotype A has been spreading throughout the country, which had been transmitted from Europe, United States, Philippines and India [6]
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