Tenofovir Disoproxil Fumarate (TDF), Emtricitabine/TDF, and Entecavir in Patients with Decompensated Chronic Hepatitis B Liver Disease

被引：316

作者：

Liaw, Yun-Fan ^{[2
]}

Sheen, I-Shyan ^{[2
]}

Lee, Chuan-Mo ^{[3
]}

Akarca, Ulus Salih ^{[4
]}

Papatheodoridis, George V. ^{[5
]}

Wong, Florence Suet-Hing ^{[6
]}

Chang, Ting-Tsung ^{[7
]}

Horban, Andrzej ^{[8
]}

Wang, Chia ^{[9
]}

Kwan, Peter ^{[10
]}

Buti, Maria ^{[11
]}

Prieto, Martin ^{[12
]}

Berg, Thomas ^{[13
]}

Kitrinos, Kathryn ^{[14
]}

Peschell, Ken ^{[14
]}

Mondou, Elsa ^{[1
,14
]}

Frederick, David ^{[14
]}

Rousseau, Franck ^{[14
]}

Schiff, Eugene R. ^{[15
]}

机构：

[1] Gilead Sci Inc, Durham, NC 27707 USA

[2] Chang Gung Univ, Chang Gung Mem Hosp, Coll Med, Liver Res Unit, Taipei, Taiwan

[3] Chang Gung Univ, Chang Gung Mem Hosp, Coll Med, Kaohsiung Med Ctr,Dept Internal Med, Kaohsiung, Taiwan

[4] Ege Univ, Tip Fak Hastanesi, Izmir, Turkey

[5] Hippokrateion Hosp, Athens, Greece

[6] Toronto Gen Hosp, Toronto, ON, Canada

[7] Natl Chen Kun Univ Hosp, Tainan, Taiwan

[8] Hosp Infect Dis, Warsaw, Poland

[9] Virginia Mason Med Ctr, Seattle, WA 98101 USA

[10] Gordon & Leslie Diamond Ctr, Vancouver, BC, Canada

[11] Hosp Gen Univ Vall dHebron, Barcelona, Spain

[12] Hosp La Fe, E-46009 Valencia, Spain

[13] Klinikum Berlin, Berlin, Germany

[14] Gilead Sci, Durham, NC USA

[15] Univ Miami, Sch Med, Miami, FL USA

来源：

HEPATOLOGY | 2011年 / 53卷 / 01期

关键词：

ADEFOVIR DIPIVOXIL; NAIVE PATIENTS; LAMIVUDINE; EFFICACY; TRANSPLANTATION; EPIDEMIOLOGY; RESISTANCE; CIRRHOSIS; SAFETY; PLUS;

D O I：

10.1002/hep.23952

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

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;53:62-72)

引用

页码：62 / 72

页数：11

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