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. 2013;10(5):567-74.
doi: 10.7150/ijms.5795. Epub 2013 Mar 15.

Adherence to medication is a more important contributor to viral breakthrough in chronic hepatitis B patients treated with entecavir than in those with Lamivudine

Hidehiro Kamezaki  1 , Tatsuo Kanda, Makoto Arai, Shuang Wu, Shingo Nakamoto, Tetsuhiro Chiba, Hitoshi Maruyama, Keiichi Fujiwara, Fumihiko Kanai, Fumio Imazeki, Fumio Nomura, Osamu Yokosuka
Affiliations

Adherence to medication is a more important contributor to viral breakthrough in chronic hepatitis B patients treated with entecavir than in those with Lamivudine

Hidehiro Kamezaki et al. Int J Med Sci. 2013.

Abstract

Viral breakthrough is related to poor adherence to medication in some chronic hepatitis B patients treated with nucleos(t)ide analogues (NAs). Our study aimed to examine how adherence to medication is associated with viral breakthrough in patients treated with NAs. A total of 203 patients (135 ETV and 68 LAM) were analyzed in this retrospective analysis. Physical examination, serum liver enzyme tests, and hepatitis B virus marker tests were performed at least every 3 months. We reviewed medical records and performed medical interviews regarding to patients' adherence to medication. Adherence rates <90% were defined as poor adherence in the present study. Cumulative viral breakthrough rates were lower in the ETV-treated patients than in the LAM-treated patients (P<0.001). Seven ETV-treated (5.1%) and 6 LAM-treated patients (8.8%) revealed poor adherence to medication (P=0.48). Among ETV-treated patients, 4 (3.1%) of 128 patients without poor adherence experienced viral breakthrough and 3 (42.8%) of 7 patients with poor adherence experienced viral breakthrough (P<0.001). Only 3 of 38 (7.8%) LAM-treated patients with viral breakthrough had poor adherence, a lower rate than the ETV-treated patients (P=0.039). Nucleoside analogue resistance mutations were observed in 50.0% of ETV- and 94.1% of LAM-treated patients with viral breakthrough (P=0.047). Viral breakthrough associated with poor adherence could be a more important issue in the treatment with especially stronger NAs, such as ETV.

Keywords: Adherence; Entecavir; Hepatitis B; Lamivudine; Viral Breakthrough..

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Conflict of interest statement

COMPETING INTERESTS: Dr. Tatsuo Kanda reports receiving lecture fees from Chugai Pharmaceutical, MSD, and Ajinomoto, and Prof. Osamu Yokosuka reports receiving grant support from Chugai Pharmaceutical, Bayer, MSD, Daiichi-Sankyo, Mitsubishi Tanabe Pharma, and Bristol-Myers Squibb.

Figures

Figure 1
Figure 1
Patients, adherence rates, and the prevalence of viral breakthrough in this study. ETV, entecavir; LAM, lamivudine.
Figure 2
Figure 2
Cumulative viral breakthrough rates. ETV, entecavir; LAM, lamivudine.
Figure 3
Figure 3
Cumulative viral breakthrough rates in lamivudine (LAM)-treated patients with HBe antigen (HBeAg)-positive at baseline. (-), maintaining HBeAg seropositivity; (+), conversion to HBeAg-seronegative.
Figure 4
Figure 4
Cumulative viral breakthrough rates in lamivudine (LAM)-treated patients who achieved HBV DNA negativity and those who did not. (-), maintaining HBV DNA positivity; (+), achieving HBV DNA negativity. HBV DNA negativity was unknown in 9 patients because of lack of data.
Figure 5
Figure 5
Association between adherence to medication and viral breakthrough.
See this image and copyright information in PMC

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