Tenofovir disoproxil fumarate (TDF), emtricitabine/TDF, and entecavir in patients with decompensated chronic hepatitis B liver disease
✍ Scribed by Yun-Fan Liaw; I-Shyan Sheen; Chuan-Mo Lee; Ulus Salih Akarca; George V. Papatheodoridis; Florence Suet-Hing Wong; Ting-Tsung Chang; Andrzej Horban; Chia Wang; Peter Kwan; Maria Buti; Martin Prieto; Thomas Berg; Kathryn Kitrinos; Ken Peschell; Elsa Mondou; David Frederick; Franck Rousseau; Eugene R. Schiff
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 271 KB
- Volume
- 53
- Category
- Article
- ISSN
- 0270-9139
No coin nor oath required. For personal study only.
✦ Synopsis
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 5 45), emtricitabine (FTC)/TDF (fixed-dose combination; n 5 45), or entecavir (ETV; n 5 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 5 0.622) as were confirmed renal parameters meeting threshold 8.9%, 6.7%, and 4.5% (P 5 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;53:62-72) C hronic hepatitis B virus (HBV) infection affects 400 million people worldwide, producing substantial morbidity and mortality. 1 About one million people die annually from complications of chronic hepatitis B (CHB). 2 Cirrhosis, liver failure, and/ or hepatocellular carcinoma (HCC) are expected to develop in 15%-40% of patients with CHB. 2 In cirrhotic patients the 5-year probability of decompensation is