title: Emergence and takeover of precore-stop mutant prior to exacerbation of e antigen-negative chronic hepatitis B after withdrawal of lamivudine therapy.
abstract: Although hepatitis B virus (HBV) precore-stop mutant (nonsense mutation at codon 28) is usually isolated from patients with hepatitis B e antigen (HBeAg)-negative hepatitis, it is unclear whether the mutant is the cause of the hepatitis flare or it is a consequence of necroinflammation. Using the amplification-created restriction site method, the ratios of precore-stop mutant were measured in serial serum samples obtained from three patients experiencing HBeAg-negative hepatitis after withdrawal of lamivudine therapy. In all three patients, the precore-stop mutant emerged and took over the viral population at least 2 months prior to the hepatitis exacerbations. After the onset of exacerbation, transient elevation of serum HBV-DNA was observed, which was followed by progressive decrease of the ratio of precore-stop mutant as well as normalization of serum transaminases. The present data indicate that at least in some patients, the precore-stop mutant is the cause but not the consequence of the flare of HBeAg-negative hepatitis.
authors.affiliation: Liver Research Unit, Chang Gung Memorial Hospital, Taipei, Taiwan. chauting@adm.cgmh.org.tw
authors.forename: Chau-Ting
authors.initials: CT
authors.lastname: Yeh
authors.forename: Wei-Pin
authors.initials: WP
authors.lastname: Lin
authors.forename: Chao-Wei
authors.initials: CW
authors.lastname: Hsu
authors.forename: Ming-Ling
authors.initials: ML
authors.lastname: Chang
authors.forename: Shi-Ming
authors.initials: SM
authors.lastname: Lin
authors.forename: I-Shyan
authors.initials: IS
authors.lastname: Sheen
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001483:Base Sequence; D018389:Codon, Nonsense; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D005260:Female; D005814:Genes, Viral; D006513:Hepatitis B e Antigens / Q000097:blood / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic
chemical_list: D000998:Antiviral Agents; D018389:Codon, Nonsense; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D019259:Lamivudine