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

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.

Distinctiveness in virological features and pathogenic potentials of subgenotypes D1, D2, D3 and D5 of Hepatitis B virus

“…Assuming that the main findings in Huh7 cells can be extrapolated to in vivo HBV infection, the variations in overall replication capacity of D-subgenotypes may underlie some of the key differences in clinical features associated with these subgenotypes. It had been reported that HBV/D2 was the major circulating D-subgenotype in patients with acute HBV infection in eastern India 35 as well as in Japan 36 and its enhanced replication capacity correlated with high viremia titers and elevated ALT levels in these patients. In contrast, D5 was conspicuously absent in the acute hepatitis B patients 35 .…”

“…It had been reported that HBV/D2 was the major circulating D-subgenotype in patients with acute HBV infection in eastern India 35 as well as in Japan 36 and its enhanced replication capacity correlated with high viremia titers and elevated ALT levels in these patients. In contrast, D5 was conspicuously absent in the acute hepatitis B patients 35 . However, among the chronically HBV/D infected patients, the viral load had been found to be highest in patients carrying HBV/D1 37 .…”

A 79-year-old Woman with Acute Hepatitis B Caused by the Infection of Subgenotype D1 Hepatitis B Virus in Japan: A Case Study

“…For instance, the peak ALT levels in acute hepatitis B with genotype A (2,137±1,088 U/L) are significantly lower than those with genotypes B (3,078±2,111 U/L) or C (2,624±1,843 U/L) ( 3 ). In a study from India, the peak ALT value in acute hepatitis B caused by genotype D tended to be lower than that caused by genotype C ( 9 ). In contrast, the peak ALT level in Ehime Prefecture with genotype D was 2,236±2,202 U/L, which was higher than that with genotype A (1,425±630 U/L) ( 4 ).…”

RESULTS OF GENOTYPING HEPATITIS VIRUS B IN HBsAg-NEGATIVE BLOOD DONORS IN ASTANA, KAZAKHSTAN

“…An indirect confirmation of our assumption is the work that showed the prevalence of HBV D2 and D3 in patients who recognized risky sexual behavior, while a group of patients who claimed to have been infected by surgery or blood transfusion shown many subgenotypes. This may be due to the fact that patients who underwent surgery and blood transfusion were exposed to several sources of infection [40].…”