1887

Abstract

To investigate the role of pre-core and basal core promoter (BCP) mutants in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (e-CHB) in Iran, strains from 30 patients and 42 anti-HBe-positive asymptomatic carriers (ASCs) were characterized. GA pre-core stop mutants, detected in 77 % of e-CHB patients and 85 % of ASCs, showed no association with virus load or aminotransferase levels. Twenty per cent of e-CHB patients and 31 % of ASCs harboured TA mutants. When this double mutation was associated with G, it was linked to a higher virus load in patients than when it was associated with A (10 vs 10 copies ml; =0·004). Interestingly, the most common BCP mutations were T and G, which were present in 33 % of e-CHB patients and 29 % of ASCs. These were associated with higher virus load and aminotransferase levels compared with patients lacking core promoter mutations, although this was not significant. The TG double mutation was only present in strains with A (<0·001), which is more frequent in strains of genotype D than in those belonging to other genotypes. On the other hand, the TA double mutation was found more frequently in association with G than with A. The TA double mutation forms a binding site for hepatocyte nuclear factor 1 (HNF1), which is constrained by A. However, the TG double mutant may form a binding site for HNF3. Thus, position 1757 affects the emergence of promoter double mutants and would predict a relative genotypic restriction of both the TA and the TG double mutants.

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2005-09-01
2019-11-20
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