Mutation of nucleotide 1,762 in the core promoter region during hepatitis B e seroconversion and its relation to liver damage in hepatitis B e antigen carriers
✍ Scribed by Lindh, Magnus; Gustavson, Carolina; Mårdberg, Kristina; Norkrans, Gunnar; Dhillon, Amar P.; Horal, Peter
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 131 KB
- Volume
- 55
- Category
- Article
- ISSN
- 0146-6615
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✦ Synopsis
In chronic hepatitis B virus (HBV) infection, mutations develop frequently at nucleotides 1,762/ 1,764 in the X protein open reading frame, where the core promoter is also located. By using a modified allele-specific polymerase chain reaction method, the longitudinal emergence of the A→T mutation at nucleotide 1,762 was studied in relation to precore mutations, genotype, and liver damage.
First, samples from 38 carriers that were drawn before and after hepatitis B e (HBe) seroconversion were tested. T-1,762 mutant strains increased during HBe seroconversion (P = 0.004). In the HBe antigen-negative (HBeAg -) phase, T-1,762 mutants were found in 71% (12 of 17) of patients without compared with 33% (6 of 18) of patients with a concomitant precore mutation that prevents HBeAg synthesis (P = 0.08).
Second, in 55 HBeAg + patients, the T-1,762 mutant was found to be associated with more liver inflammation (P = 0.04) and fibrosis (P = 0.02), as measured by histology activity index (HAI) scores.
The results show that the nucleotide (nt) 1,762 A→T mutation often develops during HBe seroconversion, particularly in strains without precore mutations that prevent HBeAg production. For unknown reasons, the T-1,762 mutant was rare in genotype B strains. The presence of a T-1,762 mutant in the HBeAg + phase may be useful for identifying immunoactivation in previously immunotolerant carriers, which could be valuable for selecting patients for interferon therapy.