Article first published online: 4 JAN 2010
Copyright © 2009 American Association for the Study of Liver Diseases
Volume 51, Issue 2, pages 422–430, February 2010
How to Cite
Chang, T.-T., Lai, C.-L., Kew Yoon, S., Lee, S. S., Coelho, H. S. M., Carrilho, F. J., Poordad, F., Halota, W., Horsmans, Y., Tsai, N., Zhang, H., Tenney, D. J., Tamez, R. and Iloeje, U. (2010), Entecavir treatment for up to 5 years in patients with hepatitis B e antigen–positive chronic hepatitis B. Hepatology, 51: 422–430. doi: 10.1002/hep.23327
Potential conflicts of interest: Ting-Tsung Chang: Research support from Bristol-Myers Squibb; Ching-Lung Lai: Research support and consultancy fees from Bristol-Myers Squibb. SeungKew Yoon: Nothing to disclose. Samuel S. Lee: Consultancy fees from Roche, Gilead, Bristol-Myers Squibb, and Novartis. Speakers' bureau for Roche, Gilead, and Bristol-Myers Squibb. Henrique Sergio M Coelho: Nothing to disclose. Flair Jose Carrilho: Research support from Bristol-Myers Squibb. Fred Poordad: Research support, speakers' bureau fees, and consultancy fees from Bristol-Myers Squibb. Waldemar Halota: Nothing to disclose. Yves Horsmans: Consultancy fees from Bristol-Myers Squibb. Naoky Tsai: Research support, speakers' bureau fees, and consultancy fees from Bristol-Myers Squibb. Hui Zhang: BMS employee. Daniel J. Tenney: BMS employee. Ricardo Tamez: BMS employee. Uchenna Iloeje: BMS employee.
In addition to the authors, the following investigators participated in the study: Asia/Pacific: Nurul Akbar, Marilyn Arguillas, You-Chen Chao, Su-Kiun Chin, Kwang-Hyub Han, Simon Huang, Ian Kronborg, Alice Lee, Jacob George, Sik-To Lai, Shou-Dong Lee, Yun-Fan Liaw, Chee Chian Lim, Gin-Ho Lo, Yiu Wing Luk, George Marinos, Ismail Merican, Rosmawati Mohamed, Eng Keat Ooi, Stuart Roberts, William Sievert, Jose Sollano, Chee Kiat Tan, Judy Lao-Tan, Tawesak Tanwandee, Shun-Sheng Wu, Felix Zano. Europe and Middle East: Edward Antuch, Yucel Batur, Anna Boron-Kaczmarska, Pavel Chalupa, Isabelle Colle, Andrzej Gladysz, Barbara Gocman, Zbigniew Gonciarz, Markus H. Heim, Vasily Isakov, Ran Tur-Kaspa, Sabahattin Kaymakoglu, Wieslaw Kryczka, Jan Kuydowicz, Yoav Lurie, Tomasz Mach, Francesco Mazzotta, Roma Modrzewska, Beat Muellhaupt, Assy Nimer, Court Pedersen, Vladimir Rafalsky, Maria Raptopoulou-Gigi, Daniel Shouval, Marian Sikora, Cihan Yurdaydin, Konstantin Zhdanov. USA and Canada: Frank H. Anderson, Thomas Boyer, Robert Brown, Robert G. Gish, Anna Lok, Gerald Minuk, Raymond Rubin, Eugene Schiff, Morris Sherman. Latin America: Antonio A. Barone, Fernando Bessone, Hugo Cheinquer, Laura E. Cisneros Garza, Luiz Guilherme Costa Lyra, Hugo Fainboim, Jorge Ferrandiz, Maria Lucia Ferraz, Fernando L. Goncales, Jr, Mario Pessoa, Marcelo Silva, Ruben Terg.
The sponsor designed the study in collaboration with expert hepatologists. The sponsor also collected the data, monitored study conduct, performed the statistical analyses, and coordinated writing of the article with all authors.
- Issue published online: 25 JAN 2010
- Article first published online: 4 JAN 2010
- Manuscript Accepted: 11 SEP 2009
- Manuscript Received: 4 MAR 2009
- Bristol-Myers Squibb
Sustained virologic suppression is a primary goal of therapy for chronic hepatitis B (CHB). In study entecavir (ETV)-022, 48 weeks of entecavir 0.5 mg was superior to lamivudine for virologic suppression for hepatitis B e antigen (HBeAg)-positive CHB. A total of 183 entecavir-treated patients from ETV-022 subsequently enrolled in study ETV-901. We present the results after up to 5 years (240 weeks) of continuous entecavir therapy. The entecavir long-term cohort consists of patients who received ≥1 year of entecavir 0.5 mg in ETV-022 and then entered ETV-901 with a treatment gap ≤35 days. In ETV-901 the entecavir dose was 1.0 mg daily. For patients with samples available at Year 5, proportions with hepatitis B virus (HBV) DNA <300 copies/mL, normal alanine aminotransferase (ALT) levels, HBeAg loss, and HBeAg seroconversion were determined. In all, 146 patients met criteria for inclusion in the entecavir long-term cohort. At Year 5, 94% (88/94) had HBV DNA <300 copies/mL and 80% (78/98) had normal ALT levels. In addition to patients who achieved serologic responses during study ETV-022, 23% (33/141) achieved HBeAg seroconversion and 1.4% (2/145) lost hepatitis B surface antigen (HBsAg) during study ETV-901. Through 5 years, entecavir resistance emerged in one patient. The safety profile of entecavir was consistent with previous reports. Conclusion: Extended therapy with entecavir through 5 years maintained or increased rates of HBV DNA suppression and ALT normalization. Additional patients also achieved HBeAg loss and seroconversion. Entecavir provides sustained viral suppression with minimal resistance during long-term treatment of HBeAg-positive CHB. (HEPATOLOGY 2010.)