title: The clinical impact of early detection of the YMDD mutant on the outcomes of long-term lamivudine therapy in patients with chronic hepatitis B.
abstract: 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 rtM2041 mutation was found. Cumulative HBeAg loss rates at 3 years was 12.5% and 57.4% in patients who had the rtM2041 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.
authors.affiliation: Department of Internal Medicine, Yonsei Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea. gihankhys@yumc.yonsei.ac.kr
authors.forename: Yong-Han
authors.initials: YH
authors.lastname: Paik
authors.forename: Kwang-Hyub
authors.initials: KH
authors.lastname: Han
authors.forename: Sun Pyo
authors.initials: SP
authors.lastname: Hong
authors.forename: Hyun Woong
authors.initials: HW
authors.lastname: Lee
authors.forename: Kwan Sik
authors.initials: KS
authors.lastname: Lee
authors.forename: Soo-Ok
authors.initials: SO
authors.lastname: Kim
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Shin
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Ahn
authors.forename: Chae Yoon
authors.initials: CY
authors.lastname: Chon
authors.forename: Young Myoung
authors.initials: YM
authors.lastname: Moon
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012150:Polymorphism, Restriction Fragment Length; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D012194:RNA-Directed DNA Polymerase