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The clinical impact of early detection of the YMDD mutant on the outcomes of long-term lamivudine therapy in patients with chronic hepatitis B.

 Yong-Han Paik  ;  Kwang-Hyub Han  ;  Sun Pyo Hong  ;  Hyun Woong Lee  ;  Kwan Sik Lee  ;  Soo-Ok Kim  ;  Ji Eun Shin  ;  Sang Hoon Ahn  ;  Chae Yoon Chon  ;  Young Myoung Moon 
 ANTIVIRAL THERAPY, Vol.11 : 447-455, 2006 
Journal Title
Issue Date
Adult ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use* ; Drug Resistance, Viral/genetics ; Female ; Genotype ; Hepatitis B e Antigens/blood ; Hepatitis B virus/drug effects ; Hepatitis B virus/enzymology ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic/drug therapy* ; Hepatitis B, Chronic/virology ; Humans ; Lamivudine/pharmacology ; Lamivudine/therapeutic use* ; Male ; Middle Aged ; Mutation* ; Polymorphism, Restriction Fragment Length ; RNA-Directed DNA Polymerase/genetics ; Reverse Transcriptase Inhibitors/pharmacology ; Reverse Transcriptase Inhibitors/therapeutic use* ; Time Factors ; Treatment Outcome
The early emergence of lamivudine (3TC)-resistant tyrosine-methionine-aspartate-aspartate (YMDD) mutants has been reported during 3TC therapy in patients with chronic hepatitis B (CHB) in hepatitis B virus (HBV)-endemic areas; however, its clinical impact during long-term 3TC therapy is unknown. This study was performed to investigate the impact of the early emergence of YMDD mutants 3 months after the initiation of treatment on the outcomes of long-term 3TC therapy in HBV e antigen (HBeAg)-positive CHB. We analysed YMDD genotypes in consecutive samples from 30 patients with HBeAg positive CHB throughout 3TC treatment using both restriction fragment length polymorphism and mass spectrometric assays. Long-term outcome was compared between patients who had YMDD mutations detected at 3 months and those who had no mutations. YMDD mutation was detected in 16 (53.3%) out of 30 patients at 3 months and only the rtM204I mutation was found. Cumulative HBeAg loss rates at 3 years was 12.5% and 57.4% in patients who had the rtM204I mutant and wild-type virus at 3 months, respectively (P=0.010). Cumulative viral breakthrough rates at 3 years was 75.0% and 14.3% in patients who had the rtM204I mutant and wild-type virus at 3 months, respectively (P=0.002). Logistic regression revealed that YMDD mutation at 3 months was significantly related to viral breakthrough within 24 months (P=0.003). In conclusion, early detection for HBV YMDD mutation at 3 months may be useful to predict the long-term outcomes of 3TC therapy in patients with HBeAg-positive CHB in HBV-endemic areas.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Paik, Yong Han(백용한)
Ahn, Sang Hoon(안상훈) ORCID logo https://orcid.org/0000-0002-3629-4624
Lee, Kwan Sik(이관식) ORCID logo https://orcid.org/0000-0002-3672-1198
Chon, Chae Yoon(전재윤)
Han, Kwang-Hyub(한광협) ORCID logo https://orcid.org/0000-0003-3960-6539
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