Hepatitis B virus: prevalence of precore/core promoter mutants in different clinical categories of Indian patients.
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.
Gandhe
S S
SS
Hepatitis Department, National Institute of Virology, Pune, India.
Chadha
M S
MS
Walimbe
A M
AM
Arankalle
V A
VA
D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000097:blood; D006509:Hepatitis B / Q000175:diagnosis* / Q000821:virology; D006512:Hepatitis B Core Antigens / Q000032:analysis* / Q000235:genetics; D006513:Hepatitis B e Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D007194:India; D008103:Liver Cirrhosis / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D012044:Regression Analysis; D016415:Sequence Alignment
D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens