Entecavir safety and effectiveness in a national cohort of treatment-naïve chronic hepatitis B patients in the US - the ENUMERATE study.
BACKGROUND
Entecavir (ETV) has been shown to be safe and efficacious in randomised controlled trials in highly selected patients with hepatitis B virus (HBV) infection.


OBJECTIVE
To determine the safety and effectiveness of ETV in 'real-world' HBV patients in the United States (US).


METHODS
Treatment-naïve HBV patients ≥18 years old who received ETV for ≥12 months between 2005 and 2013 were included in a retrospective, cohort study. Rates of ALT normalisation, undetectable HBV DNA, HBeAg and HBsAg loss/seroconversion, adverse events (AE) and clinical outcomes were evaluated.


RESULTS
Of 841 patients, 658 [65% male, 83% Asian; median age 47 years] met the inclusion criteria. 36% were HBeAg+ and 9.3% cirrhotic. 89% had abnormal ALT. Baseline median HBV DNA was 5.8 log 10 IU/mL. Median duration of ETV treatment was 4 years. Rates of ALT normalisation at 1, 3 and 5 years were 37.2%, 48.7% and 56.2% in HBeAg+ and 39.6%, 46.8% and 55.6% in HBeAg- patients. HBV DNA was undetectable at 1, 3 and 5 years in 34.6%, 64.7% and 84.6% in HBeAg+ patients, and 81.9%, 90.3% and 96.2% in HBeAg patients. Five-year cumulative probability of HBeAg loss and seroconversion was 46% and 33.7% and HBsAg loss was 4.6%. ETV was discontinued due to adverse events in 1.2% of patients. Hepatic decompensation occurred in 0.8%, liver cancer in 2.7% and death in 0.6%.


CONCLUSIONS
Entecavir treatment was safe in a large cohort of US patients, but ALT normalisation and hepatitis B virus DNA suppression rates were lower than previously reported in clinical trials.
Division of Gastroenterology & Hepatology, Oregon Health & Science University, Portland, OR, USA.
J
J
Ahn
Gastroenterology/Hepatology Division, Tufts Medical Center, Boston, MA, USA.
H M
HM
Lee
Digestive Diseases, Yale University, New Haven, CT, USA.
J K
JK
Lim
Department of Medicine, NYU Langone, New York, NY, USA.
C Q
CQ
Pan
Division of Gastroenterology & Hepatology, Stanford University, Stanford, CA, USA.
M H
MH
Nguyen
Division of Gastroenterology & Hepatology, Stanford University, Stanford, CA, USA.
W
W
Ray Kim
Division of Gastroenterology & Hepatology, Stanford University, Stanford, CA, USA.
A
A
Mannalithara
San Jose Gastroenterology, San Jose, CA, USA.
H
H
Trinh
Albert Einstein College of Medicine, New York, NY, USA.
D
D
Chu
Department of Medicine, Cedars Sinai Medical Center, Los Angeles, CA, USA.
T
T
Tran
Division of Gastroenterology, Mount Sinai Beth Israel, New York, NY, USA.
A
A
Min
Digestive Health Associates of Texas, Plano, TX, USA.
S
S
Do
Digestive Disease Center, University of Chicago, Chicago, IL, USA.
H
H
Te
Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA, USA.
K R
KR
Reddy
Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA.
A S
AS
Lok
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D055815:Young Adult
D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; C413685:entecavir; D006147:Guanine