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


CONCLUSIONS
All treatments were well tolerated in patients with decompensated liver disease due to CHB with improvement in virologic, biochemical, and clinical parameters.
Liver Research unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan.
Yun-Fan
YF
Liaw
I-Shyan
IS
Sheen
Chuan-Mo
CM
Lee
Ulus Salih
US
Akarca
George V
GV
Papatheodoridis
Florence
F
Suet-Hing Wong
Ting-Tsung
TT
Chang
Andrzej
A
Horban
Chia
C
Wang
Peter
P
Kwan
Maria
M
Buti
Martin
M
Prieto
Thomas
T
Berg
Kathryn
K
Kitrinos
Ken
K
Peschell
Elsa
E
Mondou
David
D
Frederick
Franck
F
Rousseau
Eugene R
ER
Schiff
D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000293:Adolescent; D000328:Adult; D000368:Aged; D003404:Creatinine / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004338:Drug Combinations; D000068679:Emtricitabine; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000503:physiopathology / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D000068698:Tenofovir; D019562:Viral Load
D004279:DNA, Viral; D004338:Drug Combinations; D063065:Organophosphonates; D003841:Deoxycytidine; C413685:entecavir; D006147:Guanine; D000068698:Tenofovir; D003404:Creatinine; D000068679:Emtricitabine; D000225:Adenine