title: A 96-week randomized trial of switching to entecavir in patients who achieved virological suppression on lamivudine therapy.
abstract: OBJECTIVE
  There are limited data assessing whether patients who achieved virological suppression on lamivudine but remain hepatitis B "e" antigen-positive should be switched to a more potent antiviral with a high genetic barrier to resistance or continue with lamivudine. We compared the safety and efficacy of switching with entecavir versus continuing lamivudine.
  
  
  METHODS
  This was a Phase IV, randomized, open-label, prospective study in a tertiary care setting. Seventy-three chronic hepatitis B patients who achieved virological suppression on lamivudine (serum hepatitis B virus DNA < 60 International Unit (IU)/mL) were enrolled. Entecavir or lamivudine were administered orally for up to 96 weeks. Virologic and serologic responses were measured throughout the study.
  
  
  RESULTS
  A significantly higher proportion of patients in the entecavir group achieved hepatitis B virus DNA < 60 IU/mL at Weeks 48 (100% [38/38] vs 62.8% [22/35]; P < 0.001) and 96 (97.4% [37/38] vs 57.1% [20/35]; P<0.001). A greater number of patients had virologic breakthrough (Week 96 cumulative incidence 42.9% vs 2.6%; P<0.001) and genotypic lamivudine resistance (28.6% [10/35] vs 0% [0/38]; P<0.001) in the lamivudine group. No serious adverse events or laboratory abnormalities were reported.
  
  
  CONCLUSIONS
  Even after achieving virological suppression on lamivudine therapy, the risk of emergent lamivudine resistance increases over time. Switching to entecavir resulted in a maintained virologic response and superior serologic responses versus continued lamivudine therapy. This study supports a rationale for switching to entecavir in chronic hepatitis B patients with virological suppression on lamivudine.
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, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Korea.
authors.forename: Jeong
authors.initials: J
authors.lastname: Heo
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jun Yong
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Korea.
authors.forename: Hyun Young
authors.initials: HY
authors.lastname: Woo
authors.affiliation: Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea.
authors.forename: Heon Ju
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Won Young
authors.initials: WY
authors.lastname: Tak
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Soon Ho
authors.initials: SH
authors.lastname: Um
authors.affiliation: Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Korea.
authors.forename: Ki Tae
authors.initials: KT
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Chang Wook
authors.initials: CW
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine and BioMedical Informatics Unit, Pusan National University School of Medicine, Busan, Korea.
authors.forename: Hyung Hoi
authors.initials: HH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Kwang-Hyub
authors.initials: KH
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Korea.
authors.forename: Mong
authors.initials: M
authors.lastname: Cho
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D057915:Drug Substitution; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006513:Hepatitis B e Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage*; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D006513:Hepatitis B e Antigens; D019259:Lamivudine; C413685:entecavir; D006147:Guanine
keywords: entecavir; hepatitis B; lamivudine