Emergence and takeover of precore-stop mutant prior to exacerbation of e antigen-negative chronic hepatitis B after withdrawal of lamivudine therapy.
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.
Yeh
Chau-Ting
CT
Liver Research Unit, Chang Gung Memorial Hospital, Taipei, Taiwan. chauting@adm.cgmh.org.tw
Lin
Wei-Pin
WP
Hsu
Chao-Wei
CW
Chang
Ming-Ling
ML
Lin
Shi-Ming
SM
Sheen
I-Shyan
IS
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
D000998:Antiviral Agents; D018389:Codon, Nonsense; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D019259:Lamivudine