Virological Characteristics of Acute Hepatitis B in Eastern India: Critical Differences with Chronic Infection

• Published in: PloS one 2015-11, Vol.10 (11), p.e0141741-e0141741
• Main Authors: Sarkar, Neelakshi, Pal, Ananya, Das, Dipanwita, Saha, Debraj, Biswas, Avik, Bandopadhayay, Bhaswati, Chakraborti, Mandira, Ghosh, Mrinmoy, Chakravarty, Runu
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Antigens; Chronic illnesses; Chronic infection; Cirrhosis; Deoxyribonucleic acid; DNA; DNA, Viral - genetics; Drug resistance; Entropy (Information theory); Female; Genetic variability; Genetic Variation; Genomes; Genotype; Genotype & phenotype; Genotypes; Hepatitis; Hepatitis B; Hepatitis B - epidemiology; Hepatitis B - virology; Hepatitis B Core Antigens - genetics; Hepatitis B e antigen; Hepatitis B surface antigen; Hepatitis B virus - genetics; Hepatitis B, Chronic - epidemiology; Hepatitis B, Chronic - virology; Hepatocellular carcinoma; Hepatology; HIV; Hospitals; Human immunodeficiency virus; Humans; India; Infections; Liver cancer; Liver cirrhosis; Liver diseases; Male; Medicine; Microprocessors; Middle Aged; Models, Statistical; Molecular Sequence Data; Mutation; Nucleotides - genetics; Patients; Phylogenetics; Phylogeny; Promoter Regions, Genetic; Statistical analysis; Strains (organisms); Studies; Viral infections; Viral Load; Virology; Viruses; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0141741

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.