Gut Liver.  2017 Jan;11(1):129-135. 10.5009/gnl15597.

Management of Clevudine-Resistant Chronic Hepatitis B: A Multicenter Cohort Study

  • 1Department of Internal Medicine, Wonkwang University School of Medicine, Iksan, Korea.
  • 2Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea.
  • 3Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
  • 4Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea.
  • 5Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
  • 6Department of Internal Medicine, Seoul National University College of Medicine, Seongnam, Korea.
  • 7Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea.
  • 8Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Korea.
  • 9Department of Internal Medicine, Hallym University College of Medicine, Seoul, Korea.
  • 10Bundang Jesaeng Hospital, Seongnam, Korea.
  • 11Department of Public Health, Wonkwang University Graduate School, Iksan, Korea.
  • 12Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea.


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.
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.
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.
CLV+ADV combination therapy in patients with CLV-resistant CHB more effectively suppresses HBV replication than ETV, ADV, or LAM+ADV therapy.


Clevudine; Resistance; Hepatitis B, chronic; Therapy
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