Hepatitis B e antigen-negative chronic hepatitis B

Abstract

HBeAg-negative CHB has now a worldwide distribution, developing in the course of HBeAg-positive chronic HBV infection during or after the phase of HBeAg loss and its seroconversion to anti-HBe. It is caused by replicating noncytopathic HBV mutants either unable to produce HBeAg (precore mutants) or with down-regulated transcription of the precore/core messenger RNA (BCP mutants). The most frequently encountered and stable HBeAg-negative mutants in the world are those with a novel translational precore stop codon. They are HBV genotype determined and become selected in genotypes B, C, D, and E (non-A genotypes). They prevail in South Europe, the Mediterranean basin, and Asia, whereas they are rather infrequent in the United States. The incidence of HBeAg-negative CHB is increasing in the world. The selection of HBeAg-negative HBV mutants is determined both by viral and host factors, the same being true for their ability to replicate in the presence of anti-HBe immunity. Clinical, virologic, and biochemical features as well as the natural course of HBe-negative CHB have been reviewed, and the efficacy of IFN-α and lamivudine therapy as well as the problem of viral resistance to lamivudine have been critically presented.