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

• Published in: Journal of viral hepatitis Vol. 10; no. 5; pp. 367 - 382
• Main Authors: Gandhe, S. S., Chadha, M. S., Walimbe, A. M., Arankalle, V. A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.09.2003
• Subjects: Adolescent; Adult; Aged; Base Sequence; BCP mutants; Carcinoma, Hepatocellular - pathology; Child; Child, Preschool; chronic hepatitis B; DNA, Viral - blood; fulminant hepatitis B; HBsAg carriers; HBV-DNA levels; Hepatitis B - diagnosis; Hepatitis B - virology; Hepatitis B Core Antigens - analysis; Hepatitis B Core Antigens - genetics; Hepatitis B e Antigens - analysis; Hepatitis B virus - genetics; Hepatitis B virus - immunology; Hepatitis B virus - isolation & purification; Humans; India; Liver Cirrhosis - pathology; Liver Neoplasms - pathology; Middle Aged; Molecular Sequence Data; Mutation; Pre-C mutants; Promoter Regions, Genetic - genetics; Regression Analysis; Sequence Alignment; India
• ISSN: 1352-0504; 1365-2893
• DOI: 10.1046/j.1365-2893.2003.00445.x

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.