title: Prior exposure to lamivudine increases entecavir resistance risk in chronic hepatitis B Patients without detectable lamivudine resistance.
abstract: The efficacy of entecavir (ETV) treatment in chronic hepatitis B (CHB) patients who were exposed to lamivudine (LAM) but had no detectable LAM resistance (LAM-R) is not well evaluated. In this study, we aimed to evaluate whether the probability of developing genotypic resistance to ETV in LAM-exposed patients with or without LAM-R is comparable to that in antiviral-naive patients. This retrospective cohort study included 500 consecutive patients with CHB who started ETV monotherapy at a single tertiary hospital in Korea. The patients were divided into three groups: nucleos(t)ide analogue (NA)-naive patients (group 1, n=142), patients who were previously exposed to LAM and had no currently or previously detected LAM-R (group 2, n=233), and patients with LAM-R when starting ETV (group 3, n=125). The overall median ETV treatment duration was 48.7 months. The probabilities of virologic breakthrough were significantly increased not only in group 3 (hazard ratio [HR]=14.4, P<0.001) but also in group 2 (HR=5.0, P<0.001) compared to group 1. Genotypic ETV resistance (ETV-R) developed more frequently in group 2 (HR=13.0, P=0.013) as well as group 3 (HR=43.9, P<0.001) than in group 1: the probabilities of developing ETV-R in groups 1, 2, and 3 were <1.0%, 8.0%, and 28.2%, respectively, at month 48. The results of this study indicate that ETV-R occurred more frequently in LAM-exposed patients, even though they had no detectable LAM-R, than in NA-naive patients. Therefore, LAM-exposed CHB patients, regardless of the presence or absence of LAM-R, should be monitored more cautiously for the development of ETV-R during ETV monotherapy.
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jeong-Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Yuri
authors.initials: Y
authors.lastname: Cho
authors.forename: Dong Hyeon
authors.initials: DH
authors.lastname: Lee
authors.forename: Minjong
authors.initials: M
authors.lastname: Lee
authors.forename: Jeong-ju
authors.initials: JJ
authors.lastname: Yoo
authors.forename: Won-mook
authors.initials: WM
authors.lastname: Choi
authors.forename: Young Youn
authors.initials: YY
authors.lastname: Cho
authors.forename: Yun Bin
authors.initials: YB
authors.lastname: Lee
authors.forename: Su Jong
authors.initials: SJ
authors.lastname: Yu
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Yoon
authors.forename: Hyo-Suk
authors.initials: HS
authors.lastname: Lee
authors.forename: Yoon Jun
authors.initials: YJ
authors.lastname: Kim
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D019259:Lamivudine; C413685:entecavir; D006147:Guanine