Emergence of YMDD motif mutant hepatitis B virus during long-term lamivudine therapy.
- Author:
Jong Hun LEE
1
;
Woo Won SHIN
;
Hyun Sook AHN
;
Jeong Hwan CHO
;
Myung Sik SEONG
;
Ki Tae KANG
;
Byung Hee KIM
;
Dong Yup JUNG
;
Myung Hwan ROH
;
Sang Young HAN
;
Seok Reyol CHOI
Author Information
1. Department of Internal Medicine, Dong-A University College of Medicine, Pusan, Korea.
- Publication Type:Original Article
- Keywords:
Mutant, YMDD motif, hepatitis B virus;
Lamivudine;
Hepatitis B, chronic;
Polymerase chain reaction, nested;
Polymorphism, restriction fragment length
- MeSH:
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
- From:Korean Journal of Medicine
2001;61(4):374-383
- CountryRepublic of Korea
- Language:Korean
-
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.
