Korean J Med.  2001 Oct;61(4):374-383.

Emergence of YMDD motif mutant hepatitis B virus during long-term lamivudine therapy

• Lee JH
• Shin WW
• Ahn HS
• Cho JH
• Seong MS
• Kang KT
• Kim BH
• Jung DY
• Roh MH
• Han SY
• Choi SR

Abstract

BACKGROUND: The emergence of YIDD or YVDD mutant hepatitis B virus (HBV), with point mutation in the YMDD motif of DNA polymerase gene, has been reported in patients with lamivudine treatment group. The aims of this study was to investigate the emergence of mutant HBV during long-term lamivudine therapy using nested polymerase chain reaction (PCR) method and direct DNA sequencing.
METHODS
Twenty-one chronic hepatitis B patients with HBeAg and HBV DNA positive were evaluated. During lamivudine therapy, there were reported breakthroughs of HBV DNA (over 50 pg/mL) when investigated the emergence of YMDD mutants by nested PCR method using restriction fragment length polymorphism (RFLP) in all patients. Direct DNA sequencing of HBV DNA polymerase gene including YMDD motif was also performed.
RESULTS
There were 13 patients (61.9%) with YIDD mutant and 8 patients (38.1%) with YVDD mutant. The results of direct DNA sequencing were consistent with those of nested PCR data based on RFLP. The breakthrough was occurred at 15 to 106 weeks (57.9+/-23.6). At the point of breakthrough, the level of ALT was 74.8+/-117.7 (14-546) IU/L, and it was lower than the level of ALT before the therapy.
CONCLUSION
In the long-term therapy of lamivudine, the emergence of YMDD motif mutant HBV was related to the breakthrough of HBV DNA and YIDD mutant was frequent. The nested PCR method using RFLP may be simple and sensitive to detect the YMDD motif mutant HBV.

Keyword

Mutant, YMDD motif, hepatitis B virus; Lamivudine; Hepatitis B, chronic; Polymerase chain reaction, nested; Polymorphism, restriction fragment length

MeSH Terms

DNA
Hepatitis B e Antigens
Hepatitis B virus*
Hepatitis B*
Hepatitis B, Chronic
Hepatitis*
Humans
Lamivudine*
Point Mutation
Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
Sequence Analysis, DNA
DNA
Hepatitis B e Antigens
Lamivudine