title: Management of Clevudine-Resistant Chronic Hepatitis B: A Multicenter Cohort Study.
abstract: OBJECTIVE
  Data are lacking regarding the management of chronic hepatitis B (CHB) with resistance to clevudine (CLV). This study evaluated the efficacy of different rescue therapies for CLV-resistant CHB.
  
  
  METHODS
  Patients with CLV-resistant CHB were enrolled in the cohort, and all patients developed virologic breakthrough during CLV therapy and had confirmed-genotypic resistance to CLV (rtM204I mutation) before enrollment.
  
  
  RESULTS
  Of the 107 patients, 12 received adefovir (ADV), 21 received a CLV plus ADV combination (CLV+ADV), 34 received a lamivudine plus ADV combination (LAM+ADV), and 40 received entecavir (ETV) therapy for 48 weeks. The CLV+ADV group had the lowest hepatitis B virus (HBV) DNA level (p<0.0001) and showed the greatest reduction of HBV DNA levels from baseline compared to all other groups (p=0.004) at week 48. HBV DNA was undetectable (<70 IU/mL) in 0%, 57.1%, 21.2%, and 27.5% (p=0.003) of the patients in each group, respectively, at week 48. At the end of the study, the mean alanine transaminase (ALT) level, rate of ALT normalization, and rate of hepatitis B envelope antigen loss or seroconversion did not differ between groups.
  
  
  CONCLUSIONS
  CLV+ADV combination therapy in patients with CLV-resistant CHB more effectively suppresses HBV replication than ETV, ADV, or LAM+ADV therapy.
authors.affiliation: Department of Internal Medicine, Wonkwang University School of Medicine, Iksan, Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea.
authors.forename: Hyung Joon
authors.initials: HJ
authors.lastname: Yim
authors.affiliation: Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea.
authors.forename: Young Kul
authors.initials: YK
authors.lastname: Jung
authors.affiliation: Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea.
authors.forename: Sang Jun
authors.initials: SJ
authors.lastname: Suh
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Yeon Seok
authors.initials: YS
authors.lastname: Seo
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Kim
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: Sae Hwan
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Ahn
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jeong Il
authors.initials: JI
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seongnam, Korea.
authors.forename: Sook-Hyang
authors.initials: SH
authors.lastname: Jeong
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seongnam, Korea.
authors.forename: Jin-Wook
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea.
authors.forename: Jin-Woo
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Korea.
authors.forename: In Hee
authors.initials: IH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Hallym University College of Medicine, Seoul, Korea.
authors.forename: Hyoung Su
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Bundang Jesaeng Hospital, Seongnam, Korea.
authors.forename: Sang Jong
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Public Health, Wonkwang University Graduate School, Iksan, Korea.
authors.forename: Jeong Mi
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea.
authors.forename: Seong Gyu
authors.initials: SG
authors.lastname: Hwang
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood; D019468:Disease Management; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D019259:Lamivudine; D001086:Arabinofuranosyluracil; C413685:entecavir; D006147:Guanine; C053001:adefovir; C034935:clevudine; D000225:Adenine
keywords: Clevudine; Hepatitis B, chronic; Resistance; Therapy