PREVALENCE OF PRECORE-DEFECTIVE MUTANT OF HEPATITIS-B VIRUS IN HBV CARRIERS

Two hundred and seventy-three serum specimens from hepatitis B virus ( HBV) carriers were examined for the presence of a characteristic one p oint mutation at nucleotide (nt) 1896 from the EcoRI site of the HBV g enome in the precore region (the preC mutant) using restriction fragme nt length polymorphism (RFLP) analysis. This assay approach could dete ct preC mutants or wild-type sequences when either form constituted mo re than 10% of the total sam pie. Overall, 65.5% (76/116) of HBeAg-pos itive carriers had only the preC wild-type. All HBeAg-positive asympto matic carriers (n = 14) had only the preC wild-type. In patients with chronic hepatitis B and in anti-HBe-positive asymptomatic carriers, in creased prevalence of the preC mutant was associated with the developm ent of anti-HBe antibodies and normalization of the serum alanine amin otransferase concentration. Furthermore, 27 (29.0%) of 93 HBeAg-negati ve carriers had unexpectedly preC wild-type sequences only. Direct seq uencing of the HBV precore region of HBV specimens from 24 patients re vealed no mutation at nt 1896, supporting the specificity of the RFLP analysis. These results suggest that RFLP analysis was accurate for th e detection of the preC mutation and that the absence of serum HBeAg c annot be explained solely by the dominance of the preC mutant. (C) 199 5 Wiley-Liss, Inc.