, Volume 40, Issue 1, pp 1-7

Nucleotide sequence analysis of precore and proximal core regions in patients with chronic hepatitis B treated with interferon

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Abstract

The aim of the study was to estimate the prevalence of HBeAg defective mutants among patients with chronic hepatitis B (CHB) in the United States and to study the effect of interferon-α (IFN-α) on determining the occurrence of mutations in the HBV precore and proximal core regions. Twenty CHB patients who were treated with IFN-α were studied. Initially, all were HBV DNA positive by dot-blot hybridization; 17/20 were HBeAg positive, and 3/20 were anti-HBe positive. The precore (87 nt) and proximal core (81 nt) regions were sequenced after PCR amplification by the dideoxy chain termination method. In pretreatment sera, 15/20 patients harbored wild-type HBV only, while in 5/20 at least one nucleotide substitution was found. Mutations that prevent HBeAg synthesis were found in three patients, all of whom had G-to-A substitution at nt 1896 and two of them were anti-HBe positive. Follow-up sera were available in 18 patients. With respect to pretreatment specimen, 15/18 patients had no changes in the sequenced regions after therapy. Sequence changes were observed in the remaining three patients: In one an HBeAg defective strain was replaced by a wild-type strain; in the second a wild-type strain was replaced by an HBeAg defective strain; and in the third two mutations changing the deduced amino acid sequence of the core protein developed in the wild-type strain. In conclusion, most of our patients (85%) were initially infected by HBV strains having no mutations that prevented HBeAg synthesis. IFN-α therapy infrequently resulted in the appearance of mutations in the precore and proximal core regions.

This study was supported by grant CR20 (to J.R.) from the Mayo Clinic and Foundation, and in part by Public Health Service grants AI32403, AR41497, and AI30548 from the National Institutes of Health (to D.H.P.).