Association of HBV DNA and ALT Level with YMDD motif Mutation Type in Lamivudine Resistance for Chronic Hepatitis B

BACKGROUND: The emergence of lamivudine resistant hepatitis B virus(HBV), with point mutation in the YMDD motif of DNA polymerase gene, has been reported in chronic hepatitis B patients with lamivudine treatment. The aim of this study was to investigate the distribution patterns and clinical aspects of lamivudine resistant HBV mutant during long-term lamivudine therapy. METHOD: We retrospectively analyzed 93 consecutive patients with chronic hepatitis B or liver cirrhosis who were lamivudine resistant. Patients received 100 mg of lamivudine per day orally for at least 9 months. The duration of lamivudine therapy was from 9 to 94 months(mean 36.2 months). YMDD motif mutants and serum HBV DNA were investigated by using restriction fragment mass polymorphism(RFMP) and Digene® Hybrid capture II assay, respectively. RESULTS: The HBV DNA breakthrough was occurred at 22.8±14.9(5-79) months after starting lamivudine therapy. At the point of breakthrough, the level of ALT was 186.3±199.7(15-1469) U/L and HBV DNA was 7.65±0.09(5.23-9.09) log10 copies/mL. They were lower than the level of ALT and HBV DNA before the therapy. Among 93 patients, 42 patients(45.2%) and 27 patients(29.0%) had YIDD and YVDD mutant, respectively. 24 patients(25.8%) had YIDD/YVDD mixed mutant. There was not significant to the level of ALT, HBV DNA at the point of viral breakthrough between three groups. Additional mutation, `L-to-M' in 528th amino acid was found at 78 patients(83.9%)(64.2% with YIDD mutant and 100% with YVDD mutant). CONCLUSION: During the long-term therapy of lamivudine in patients with chronic hepatitis B or liver cirrhosis, YIDD mutant was more frequent than YVDD mutant, YIDD/YVDD mutant was found frequently. Between mutant groups, the level of ALT and HBV DNA at the point of viral breakthrough was not significant.

Author dc:creator

• 최, 재명

Contributors dc:contributor

• 조, 성원
• 대학원 의학과
• 200524213

• 만성 B형간염
• 라미부딘
• YMDD motif 변이형
• 제한효소분절질량다형성
• ALT Level

Language dc:language

ko

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000001885
000000001885

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/1624