title: Low efficacy of entecavir therapy in adefovir-refractory hepatitis B patients with prior lamivudine resistance.
abstract: We determined the virologic response, incidence of entecavir resistance, and evolution of lamivudine and adefovir-resistant mutants during entecavir (ETV) therapy in adefovir-refractory patients with prior lamivudine resistance. Forty adefovir-refractory chronic hepatitis B patients with prior lamivudine resistance who had received entecavir for > or = 6 months were included and monitored for virologic response and entecavir resistance. Ten per cent of patients achieved HBV DNA < 50 copies/mL by PCR after 24 weeks of ETV therapy, and an initial virologic response was observed in 12 of 40 patients (30%). Higher pretreatment ALT (P = 0.039) and the presence of the rtL180M mutation (P = 0.038) were associated with an initial virologic response. During a mean follow-up of 11.4 months, four patients (10%) experienced virologic breakthrough, while ETV-resistant mutants were detected in six patients (15%). YMDD and adefovir-resistant mutants were detected in 57 and 35% of patients at baseline, respectively. At 48 weeks of therapy, 96 and 4% of patients had YMDD and adefovir-resistant mutants, respectively. These data suggest an early development of ETV resistance and low antiviral response during ETV therapy in adefovir-refractory patients with prior lamivudine resistance.
authors.affiliation: Department of Gastroeneterlogy, Ajou University School of Medicine, San-5 Wonchon-Dong, Yountong-Ku, Suwon, 442-821, South Korea. sung_woncho@hotmail.com
authors.forename: S W
authors.initials: SW
authors.lastname: Cho
authors.forename: K H
authors.initials: KH
authors.lastname: Koh
authors.forename: J Y
authors.initials: JY
authors.lastname: Cheong
authors.forename: M H
authors.initials: MH
authors.lastname: Lee
authors.forename: S P
authors.initials: SP
authors.lastname: Hong
authors.forename: W D
authors.initials: WD
authors.lastname: Yoo
authors.forename: S-O
authors.initials: SO
authors.lastname: Kim
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral; D005260:Female; D005500:Follow-Up Studies; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000187:drug effects*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000494:pharmacology*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000225:Adenine