Identification of a hepatitis B virus S gene mutant in lamivudine-treated patients experiencing HBsAg seroclearance.
OBJECTIVE
Seroclearance of hepatitis B virus (HBV) surface antigen (HBsAg) is a rare event in chronic hepatitis B patients receiving lamivudine therapy. It is generally believed to be a benevolent sign, implicating clearance of viremia. The aim of this study is to examine the authenticity of this dogma.


METHODS
In a 5-year period, 11 patients treated with lamivudine experienced seroclearance of HBsAg. The clinical data were examined. The HBV S gene sequences derived from the patient's serum samples before and after seroclearance of HBsAg were analyzed.


RESULTS
Serum HBV-DNA could be detected by nested polymerase chain reaction (PCR) in all 11 patients, by 1-step PCR in 8, and by Cobas Amplicor HBV-DNA test (>200 copies/mL) in 5. A mutation hot spot, P120A in the S gene, was identified in 6 of the 11 patients. Site-directed mutagenesis experiments indicated that the Ausria-II RIA test failed to detect this mutant. Decreased sensitivity of detection was also observed when other monoclonal antibodies were applied.


CONCLUSIONS
Seroclearance of HBsAg during lamivudine therapy may not indicate viral clearance. Specifically, it may be caused by a point mutation in the S gene, which results in detection failure. In such patients, further verification and follow-up using a sensitive HBV-DNA test are advised.
Hsu
Chao-Wei
CW
Liver Research Unit, Chang Gung Memorial Hospital, Taipei, Taiwan.
Yeh
Chau-Ting
CT
Chang
Ming-Ling
ML
Liaw
Yun-Fan
YF
D000328:Adult; D019943:Amino Acid Substitution; D002460:Cell Line; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007124:Immunoenzyme Techniques; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D011237:Predictive Value of Tests; D011379:Prognosis; D011498:Protein Precursors / Q000097:blood / Q000235:genetics; D011863:Radioimmunoassay; D011933:Reagent Kits, Diagnostic; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D012680:Sensitivity and Specificity; D013997:Time Factors; D014162:Transfection; D016896:Treatment Outcome; D014766:Viremia / Q000188:drug therapy / Q000821:virology
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; D011933:Reagent Kits, Diagnostic; D018894:Reverse Transcriptase Inhibitors; C050806:presurface protein 1, hepatitis B surface antigen; C050807:presurface protein 2, hepatitis B surface antigen; D019259:Lamivudine