Changes of precore nucleic acid sequence in chronic hepatitis B patients with and without interferon administration.

Abstract

The aim of this study was to investigate the effect of interferon-α (IFN-α) on the occurrence of mutations in the precore region of the hepatitis B virus (HBV). We studied 24 patients with chronic hepatitis B; 11 were non-responders to IFN therapy and 13 were untreated patients. After HBV DNA extraction from serum, nested PCR of the precore region and direct sequencing was performed. Among the baseline sera of 24 patients, three types of mutation G to A at nucleotide 1896 (A1896), 1899 (A1899), and A to T at nucleotide 1846(T1846) were found in 12 patients. The prevalence of A1896 was 45.8% (11/24), A1899 8.3% (2/24), and T1846 12.5% (3/24), respectively. A1896 was found in six out of 18 HBeAg-positive patients and in five out of six anti-HBE-positive patients. During the 1 year follow-up period, sequence changes were found in five out of 13 untreated patients: A wild-type strain was replaced by a mutant A1896 strain in two patients; mixed viral populations of wild-type strains and mutant A1896 strains were replaced by a mutant A1896 strain in one patient; and a mutant A1896 strain was replaced by a wild-type strain in two patients. In contrast, ten out of 11 non-responders had no changes in the precore region after therapy during follow-up period. A shift from predominantly wild-type strains to predominantly mutant A1896 strains was found in the remaining one non-responder. In conclusion, sequence changes in the precore region occur frequently during the course of chronic hepatitis B virus infection. IFN-α therapy may decrease the appearance of mutations in the precore region in non-responders.