Hepatitis B virus: prevalence of precore/core promoter mutants in different clinical categories of Indian patients

Abstract

To determine the association of precore (Pre-C)/basal core promoter (BCP) mutants with clinical outcome of hepatitis B in Western India, 192 hepatitis B virus (HBV) infected individuals were investigated. HBV-DNA PCR positivity among asymptomatic hepatitis B surface antigen (HBsAg) positive carriers (61/100) was lower (P < 0.0001) than chronic hepatitis B (CHB), acute (P = 0.0001), and fulminant hepatitis B patients (P=0.047). Pre-C status was based on restriction fragment length polymorphism (RFLP, n=153) and sequencing (n=118). Prevalence of Pre-C mutants was higher among carriers (23/61) than CHB (10/62, P=0.0071) or acute (3/22; P=0.037) patients. Children from carrier and CHB categories showed significantly higher circulation of Pre-C-wild than mutant HBV. Clinical manifestations were independent of BCP mutations (1762/64-T/A). Hepatitis B e antigen (HBeAg) negative CHB patients [62.5% (15/24)] were circulating wild HBV. Higher HBV-DNA levels were associated with chronic hepatitis and HBeAg positivity, whilst Pre-C mutant positives had lower levels. BCP mutations did not affect HBV-DNA levels. Multivariate regression analysis identified HBeAg (OR=4.3) and Pre-C mutants (OR=3.1) to be associated with chronic hepatitis and carriers respectively. In a separate sub-set analysis (n=59), HBV-DNA level was identified as the only variable. In conclusion, chronic or fulminant hepatitis B was not associated with Pre-C or BCP mutants and switching over to Pre-C mutant was beneficial for the infected individual in maintaining disease free status for extended periods.