title: Long-term outcomes and dynamics of mutants associated with lamivudine-adefovir rescue therapy in patients with lamivudine-resistant chronic hepatitis B.
abstract: OBJECTIVE
  To investigate the association between the baseline profiles and dynamics of hepatitis B virus (HBV) DNA polymerase gene mutations and the long-term virological response of lamivudine (LAM)-adefovir (ADV) combination therapy in patients with LAM-resistant chronic hepatitis B.
  
  
  METHODS
  Seventy-five patients who received LAM-ADV combination therapy for more than 12 months were analyzed. Restriction fragment mass polymorphism assays were used to detect and monitor the dynamics of LAM- and ADV-resistant mutations.
  
  
  RESULTS
  The median duration of LAMADV combination therapy was 26 months (range, 12 to 58 months). The baseline mutation profiles, rtM204I (p=0.992), rtM204I/V (p=0.177), and rtL180M (p=0.051), were not correlated with the cumulative virological response, and the baseline HBV DNA level (p=0.032) was the only independent predictive factor for cumulative virological response. Tests for LAM- and ADV-resistant mutations were performed in 12 suboptimal responders in weeks 48 and 96. The population of rtM204 mutants persisted or increased in 8 of 12 patients, and rtA181T mutants newly emerged as a minor population in four patients until 96 weeks. Nevertheless, the viral loads progressively decreased during rescue therapy, and these dynamics did not correlate with virological response.
  
  
  CONCLUSIONS
  The baseline profile and dynamics of LAM-resistant mutations during LAM-ADV combination therapy are not associated with a virological response.
authors.affiliation: Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Jihyun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Sae Hwan
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Hong Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Kanghyug
authors.initials: K
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Soung Won
authors.initials: SW
authors.lastname: Jeong
authors.affiliation: Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Sang Gyune
authors.initials: SG
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Jang
authors.affiliation: Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Young Seok
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Boo Sung
authors.initials: BS
authors.lastname: Kim
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D019259:Lamivudine; C053001:adefovir; D004259:DNA-Directed DNA Polymerase; D000225:Adenine
keywords: Hepatitis B virus; Lamivudine resistance; Mutation; Restric-tion fragment mass polymorphism