Tenofovir disoproxil fumarate (TDF), emtricitabine/TDF, and ... : Hepatology (original) (raw)

Viral Hepatitis

Tenofovir disoproxil fumarate (TDF), emtricitabine/TDF, and entecavir in patients with decompensated chronic hepatitis B liver disease

Liaw, Yun-Fan1; Sheen, I-Shyan1; Lee, Chuan-Mo2; Akarca, Ulus Salih3; Papatheodoridis, George V.4; Wong, Florence Suet-Hing5; Chang, Ting-Tsung6; Horban, Andrzej7; Wang, Chia8; Kwan, Peter9; Buti, Maria10; Prieto, Martin11; Berg, Thomas12; Kitrinos, Kathryn13; Peschell, Ken13; Mondou, Elsa13,*; Frederick, David13; Rousseau, Franck13; Schiff, Eugene R.14

1_Liver Research unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan_

2_Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan_

3_Ege Universitesi Tip Fakultesi Hastanesi. Izmir, Turkey_

4_Ippokration General Hospital of Athens, Athens, Greece_

5_Toronto General Hospital, Toronto, ON, Canada_

6_National Chen Kun University Hospital, Tainan, Taiwan_

7_Hospital of Infectious Diseases, Warsaw, Poland_

8_Virginia Mason Medical Center, Seattle, WA, USA_

9_The Gordon and Leslie Diamond Centre, Vancouver, BC, Canada_

10_Hospital General Universitari Vall d'Hebron, Barcelona, Spain_

11_Hospital La Fe, Valencia, Spain_

12_Charite Campus Virchow-Klinikum, Berlin, Germany_

13_Gilead Sciences, Durham, NC, USA_

14_University of Miami School of Medicine, Miami, FL, USA_

*Gilead Sciences Inc., 4 University Place, 4611 University Drive, Durham, NC 27707

Email:[email protected]; fax: 919-493-5925

Received 16 July 2010; Accepted 19 August 2010

Published online 27 October 2010 in Wiley Online Library (wileyonlinelibrary.com).

Potential conflict of interest: Nothing to report.

Abstract

Data are limited on the safety and effectiveness of oral antivirals other than lamivudine and adefovir dipivoxil for treatment of chronic hepatitis B (CHB) in patients with decompensated liver disease. This Phase 2, double-blind study randomized 112 patients with CHB and decompensated liver disease to receive either tenofovir disoproxil fumarate (TDF; n = 45), emtricitabine (FTC)/TDF (fixed-dose combination; n = 45), or entecavir (ETV; n = 22). The primary endpoint was safety; more specifically, tolerability failure (adverse events resulting in permanent treatment discontinuation) and confirmed serum creatinine increase ≥0.5 mg/dL from baseline or confirmed serum phosphorus <2 mg/dL. Patients with insufficient viral suppression (e.g., confirmed HBV DNA ≥400 copies/mL at week 8 or 24) could begin open-label FTC/TDF but were considered failures in this interim week 48 analysis for efficacy endpoints. Tolerability failure was infrequent across arms: 6.7% TDF, 4.4% FTC/TDF, and 9.1% ETV ( P = 0.622) as were confirmed renal parameters meeting threshold 8.9%, 6.7%, and 4.5% ( P = 1.000), respectively. Six patients died (none considered related to study drug) and six received liver transplants (none had HBV recurrence). The adverse event and laboratory profiles were consistent with advanced liver disease and complications, with no unexpected safety signals. At week 48, HBV DNA was <400 copies/mL (69 IU/mL) in 70.5% (TDF), 87.8% (FTC/TDF), and 72.7% (ETV) of patients. Proportions with normal alanine aminotransferase were: 57% (TDF), 76% (FTC/TDF), and 55% (ETV). Hepatitis B e antigen (HBeAg) loss/seroconversion occurred in 21%/21% (TDF), 27%/13% (FTC/TDF), and 0%/0% (ETV). Child-Turcotte-Pugh and Modification for End-stage Liver Disease scores improved in all groups.

Conclusion:

All treatments were well tolerated in patients with decompensated liver disease due to CHB with improvement in virologic, biochemical, and clinical parameters. (Hepatology 2011.)