International Journal of Medical Sciences

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15 December 2018

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Int J Med Sci 2013; 10(6):647-652. doi:10.7150/ijms.5904

Research Paper

Efficacy of Lamivudine or Entecavir against Virological Rebound after Achieving HBV DNA Negativity in Chronic Hepatitis B Patients

Tomoo Miyauchi1,*, Tatsuo Kanda1,*, ✉, Masami Shinozaki2, Hidehiro Kamezaki1, Shuang Wu1, Shingo Nakamoto1, Kazuki Kato3, Makoto Arai1, Shigeru Mikami4, Nobuyuki Sugiura5, Michio Kimura3, Nobuaki Goto2, Fumio Imazeki1,6, Osamu Yokosuka1

1. Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba (260-8677), Japan.
2. Department of Gastroenterology, Numazu City Hospital, Numazu (410-0302), Japan.
3. Department of Medicine, Social Insurance Funabashi Central Hospital, Funabashi (273-8556), Japan.
4. Department of Gastroenterology, Kikkoman General Hospital, Noda (278-0005), Japan.
5. Department of Gastroenterology, National Hospital Organization Chiba Medical Center, Chiba (260-8606), Japan.
6. Safety and Health Organization, Chiba University, Chiba (263-8522), Japan.
*These authors contributed equally.


Nucleos(t)ide analogues (NAs) lead to viral suppression and undetectable hepatitis B virus (HBV) DNA in some individuals infected with HBV, but the rate of virological rebound has been unknown in such patients. We examined the prevalence of virological rebound of HBV DNA among NA-treated patients with undetectable HBV DNA. We retrospectively analyzed 303 consecutive patients [158 entecavir (ETV)- and 145 lamivudine (LAM)-treated] who achieved HBV DNA negativity, defined as HBV DNA < 3.7 log IU/mL for at least 3 months. They were followed up and their features, including their rates of viral breakthrough, were determined. Viral rebound after HBV DNA negativity was not observed in the ETV-group. Viral rebound after HBV DNA negativity occurred in 38.7% of 62 HBe antigen-positive patients in the LAM-group. On multivariate analysis, age was an independent factor for viral breakthrough among these patients (P = 0.035). Viral rebound after HBV DNA negativity occurred in 29.1% of 79 HBe antigen-negative patients in the LAM-group. Differently from LAM, ETV could inhibit HBV replication once HBV DNA negativity was achieved. In contrast, LAM could not inhibit HBV replication even if HBV negativity was achieved in the early phase. Attention should be paid to these features in clinical practice.

Keywords: Entecavir, HBeAg, HBV DNA, Lamivudine, Virological rebound.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See for full terms and conditions.
How to cite this article:
Miyauchi T, Kanda T, Shinozaki M, Kamezaki H, Wu S, Nakamoto S, Kato K, Arai M, Mikami S, Sugiura N, Kimura M, Goto N, Imazeki F, Yokosuka O. Efficacy of Lamivudine or Entecavir against Virological Rebound after Achieving HBV DNA Negativity in Chronic Hepatitis B Patients. Int J Med Sci 2013; 10(6):647-652. doi:10.7150/ijms.5904. Available from