Digestive Diseases and Sciences

, Volume 57, Issue 5, pp 1358–1365 | Cite as

Efficacy of Entecavir and Adefovir Combination Therapy for Patients with Lamivudine- and Entecavir-Resistant Chronic Hepatitis B

  • Jung Won Jeon
  • Hyun Phil Shin
  • Joung Il Lee
  • Kwang Ro Joo
  • Jae Myung Cha
  • Jae Jun Park
  • Jun Uk Lim
  • Kyuseong Lim
  • Sunyong Kim
Original Article



The optimal treatment of patients with chronic hepatitis B (CHB) who develop resistance to both lamivudine (LMV) and entecavir (ETV) after sequential monotherapy of LMV and ETV remains little known.


We evaluated the efficacy of entecavir (ETV) plus adefovir dipivoxil (ADV) combination therapy for patients with resistance to LMV and ETV. We reviewed the medical records of 12 patients, and treated all 12 patients with ETV plus ADV combination therapy for at least 18 months. Quantitative hepatitis B virus (HBV) DNA levels, serologic markers, and hepatic panel values were monitored at baseline and 3-month intervals thereafter for 18 months.


The baseline mean serum HBV DNA level was 7.26 ± 1.11 log10 copies/ml. The mean reductions in serum HBV DNA levels from baseline to 3, 6, 9, 12, 15, and 18 months were −1.98 ± 1.03, −2.87 ± 1.02, −3.32 ± 1.10, −3.92 ± 1.30, −4.36 ± 1.22, and −4.57 ± 1.18 log10 copies/ml, respectively. Complete virological response (HBV DNA of <2 log10 copies/ml) at 6, 12, and 18 months was observed in 1 (8.3%), 4 (33.3%), and 6 (50.0%) patients, respectively. The 2 patients with baseline HBV DNA of <6 log10 copies/ml achieved complete virological response at 18 months, while 4 of 10 patients with baseline HBV DNA of ≥6 log10 copies/ml achieved complete virological response at 18 months. None of the 12 patients experienced virological breakthrough during follow-up.


ETV plus ADV combination therapy effectively reduced serum HBV DNA levels in patients with CHB who developed resistance to both LMV and ETV. Additional long-term studies are needed to assess the effect of long-term treatment with these drugs.


Chronic hepatitis B Resistance Lamivudine Entecavir Adefovir 


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Jung Won Jeon
    • 1
  • Hyun Phil Shin
    • 1
  • Joung Il Lee
    • 1
  • Kwang Ro Joo
    • 1
  • Jae Myung Cha
    • 1
  • Jae Jun Park
    • 1
  • Jun Uk Lim
    • 1
  • Kyuseong Lim
    • 1
  • Sunyong Kim
    • 1
  1. 1.Department of Internal Medicine, College of MedicineKyung Hee UniversitySeoulKorea

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