Identification of a Hepatitis B Virus S Gene Mutant in Lamivudine-Treated Patien

February 6, 2007

Gastroenterology. 2006 Dec 3; [Epub ahead of print]

Identification of a Hepatitis B Virus S Gene Mutant in Lamivudine-Treated

Patients Experiencing HBsAg Seroclearance.

Hsu CW, Yeh CT, Chang ML, Liaw YF.

Liver Research Unit, Chang Gung Memorial Hospital, Taipei, Taiwan.

BACKGROUND & AIMS: 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.

PMID: 17258721 [PubMed - as supplied by publisher]

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