Hepatitis B genotypes and precore/basal core promoter mutants in HBeAg-negative chronic hepatitis B

Mutations in the precore stop codon (G1896A) and the basal core promoter (A1762T and G1764A) are frequently found in hepatitis B envelope antigen (HBeAg)-negative chronic hepatitis B. However, the clinical significance of these mutations remains controversial. We therefore investigated the influence of hepatitis B virus (HBV) genotypes, as well as precore/basal core promoter mutants, on the clinical and virological features of patients with HBeAg-negative chronic hepatitis B.

Serum samples from 37 patients with HBeAg-negative chronic hepatitis B were collected for serological and molecular assays. The precore and basal core promoter regions were amplified by polymerase chain reaction and the amplicons were directly sequenced and analyzed. HBV genotype was determined by polymerase chain reaction-restriction fragment length polymorphism.

Most of the patients had detectable serum HBV DNA, and genotypes B and C were the predominant strains. The overall prevalence of the precore stop codon mutant and basal core promoter mutant was 67% and 60%, respectively. The baseline clinical and virological features of patients with genotype B and genotype C infection were comparable. However, in the patients with precore/basal core promoter dual mutations there was a significantly lower proportion of individuals with a high detectable serum HBV DNA level (>100pg/ml) than in the patients with either the precore stop codon mutation alone or the basal core promoter mutation alone (P = 0.04 by the logistic regression test for the trend).

Our data suggest a high prevalence of precore stop codon and basal core promoter mutation in Taiwanese patients with HBeAg-negative chronic hepatitis B, and the influence of the basal core promoter mutation on HBV replication is modulated by the emergence of the precore stop codon mutation.