Article first published online: 27 AUG 2012
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 56, Issue 6, pages 2018–2026, December 2012
How to Cite
Murray, K. F., Szenborn, L., Wysocki, J., Rossi, S., Corsa, A. C., Dinh, P., McHutchison, J., Pang, P. S., Luminos, L. M., Pawlowska, M. and Mizerski, J. (2012), Randomized, placebo-controlled trial of tenofovir disoproxil fumarate in adolescents with chronic hepatitis B. Hepatology, 56: 2018–2026. doi: 10.1002/hep.25818
Potential conflict of interest: K. M. is a consultant to Gilead, Roche, and Merck and holds stock ownership in Merck; S. R. is an employee of Gilead and holds stock ownership; A. C. is an employee of Gilead and holds stock ownership; P. D. is an employee of Gilead and holds stock ownership; J. M. is an employee of Gilead and holds stock ownership; P. P. is an employee of Gilead and holds stock ownership.
In addition to the authors, the following investigators participated in the study: H. Zhelev, M. Bosheva (Bulgaria); F. Gottrand, A. Lachaux (France); J. Kuydowicz, D. Lebensztejn, M. Marczynska, W. Slużewski (Poland); A. Constantinescu, D. Farcau (Romania); P. Jara Vega, C. Ribes-Koninckx (Spain); F. Ozgenc (Turkey); P. Harmatz, G. Subbarao (United States).
See Editorial on Page 2016
- Issue published online: 4 DEC 2012
- Article first published online: 27 AUG 2012
- Accepted manuscript online: 27 APR 2012 10:32AM EST
- Manuscript Accepted: 24 APR 2012
- Manuscript Received: 31 JAN 2012
- Gilead Sciences, Inc.
Tenofovir disoproxil fumarate (DF) is highly effective for the suppression of hepatitis B virus (HBV) in chronically infected adults. This study evaluated the safety and efficacy of tenofovir DF in adolescents with chronic hepatitis B (CHB). In this double-blind, placebo-controlled trial, adolescents 12 to <18 years of age with CHB were randomized to tenofovir DF 300 mg (n = 52) or placebo (n = 54) once daily for 72 weeks. The primary endpoint was virologic response (HBV DNA <400 copies/mL) at week 72. One hundred six patients were enrolled; 101 patients completed 72 weeks of treatment. At baseline, 91% of patients were hepatitis B e antigen–positive and 85% had prior exposure to HBV therapy. A virologic response was observed in 89% (46/52) of patients who received tenofovir DF and 0% (0/54) of patients who received placebo (P < 0.001). Treatment response was not affected by prior HBV treatment. Furthermore, no resistance to tenofovir DF developed through week 72. Among patients with an alanine aminotransferase (ALT) level greater than the upper limit of normal at baseline, normalization of ALT occurred in 74% of patients receiving tenofovir DF and 31% of patients receiving placebo (P < 0.001). The rate of grade 3/4 adverse events was higher among patients treated with placebo (24%) than patients treated with tenofovir DF (10%). No patients met the safety endpoint of a 6% decrease in spine bone mineral density at week 72. Conclusion: Tenofovir DF therapy in HBV-infected adolescents was well tolerated and highly effective at suppressing HBV DNA and normalizing ALT values in both treatment-naïve adolescents and those with prior exposure to HBV therapy. (HEPATOLOGY 2012;56:2018–2026)