title: Off-treatment virologic relapse and outcomes of re-treatment in chronic hepatitis B patients who achieved complete viral suppression with oral nucleos(t)ide analogs.
abstract: BACKGROUND
  The durability of off-treatment virologic responses has not been fully elucidated in chronic hepatitis B (CHB) patients who have previously achieved complete virologic suppression with nucleos(t)ide analog (NA) therapy. This study aimed to assess off-treatment virologic relapse rates and to characterize the outcomes of subsequent re-treatment in CHB patients who have discontinued oral NA following complete virologic suppression.
  
  
  METHODS
  Ninety-five CHB patients who showed complete virologic suppression were withdrawn from NAs: entecavir, lamivudine, and clevudine in 67, 15, and 13 patients, respectively. Consolidation therapy was given for 6 and 12 months for HBeAg-positive and -negative CHB, respectively, before cessation. Virologic relapse was managed with the same NA that had induced complete virologic response before discontinuation.
  
  
  RESULTS
  The cumulative rates of virologic relapse at 12 and 24 months were 73.8% and 87.1%, respectively. The relapse rates were independent of HBeAg positivity, HBeAg seroconversion, and type of oral NA. In a multivariate analysis, duration of oral NA therapy was the only significant predicting factor associated with off-treatment virologic relapse. Although the majority of patients regained complete virologic suppression, some patients did not respond to re-treatment with the initial NA and developed genotypic resistance.
  
  
  CONCLUSIONS
  NA consolidation therapy for 6 and 12 months is associated with high off-treatment virologic relapse in HBeAg-positive and -negative CHB patients, respectively. Drugs with high genetic barriers to resistance should be considered as a rescue therapy for off-treatment relapse in CHB.
authors.forename: Hyung Rae
authors.initials: HR
authors.lastname: Sohn
authors.forename: Bo Young
authors.initials: BY
authors.lastname: Min
authors.forename: Joon Chang
authors.initials: JC
authors.lastname: Song
authors.forename: Mun Hyuk
authors.initials: MH
authors.lastname: Seong
authors.forename: Sang Soo
authors.initials: SS
authors.lastname: Lee
authors.forename: Eun Sun
authors.initials: ES
authors.lastname: Jang
authors.forename: Cheol Min
authors.initials: CM
authors.lastname: Shin
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Park
authors.forename: Jin-Hyeok
authors.initials: JH
authors.lastname: Hwang
authors.forename: Sook-Hyang
authors.initials: SH
authors.lastname: Jeong
authors.forename: Nayoung
authors.initials: N
authors.lastname: Kim
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707, South Korea. kimjw@snubh.org.
authors.forename: Jin-Wook
authors.initials: JW
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012008:Recurrence; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D019259:Lamivudine; D001086:Arabinofuranosyluracil; C413685:entecavir; D006147:Guanine; C034935:clevudine