Lower Observed Hepatocellular Carcinoma Incidence in Chronic Hepatitis B Patients Treated With Entecavir: Results of the ENUMERATE Study.
Data from the United States are lacking regarding the impact of entecavir (ETV) on the risk of hepatocellular carcinoma (HCC). Our aim is to determine whether treatment with ETV is associated with a reduced HCC risk by calculating the expected HCC incidence based on the Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B (REACH-B) model and comparing it with the observed HCC incidence.



The incidence of HCC in US patients treated with ETV between 2005 and 2013 in a retrospective cohort was obtained. The predicted HCC incidence was calculated using the REACH-B model. The standardized incidence ratios (SIRs) were calculated as a ratio of observed over predicted HCC cases.



Of 841 patients, 646 (65% male, 84% Asian, median age 47 years, 36% hepatitis B e antigen positive, 9.4% with cirrhosis) met the inclusion criteria. Over a median follow-up of 4 years, 17 (2.6%) cases of HCC were diagnosed, including 8 out of 61 (13.1%) patients with cirrhosis and 9 out of 585 (1.5%) without cirrhosis. Compared with those without HCC, the 17 patients with HCC were older at 53 years vs. 47 years and more likely to have cirrhosis at 47.1% vs. 8.4%. Among patients without cirrhosis, the observed HCC incidence was significantly lower than predicted by the fourth year (SIR, 0.37; 95% confidence interval: 0.166-0.82). A sensitivity analysis that comprised all patients, including those with cirrhosis, showed that at the maximum follow-up time of 8.2 years, a significantly lower than predicted HCC incidence was noted with an SIR of 0.56 (95% confidence interval: 0.35-0.905).



Based on the REACH-B model, long-term ETV therapy was associated with a lower than predicted HCC incidence. However, the risk of HCC persisted, and careful HCC surveillance remains warranted despite the anti-viral treatment.
Division of Gastroenterology and Hepatology, Oregon Health and Science University, Portland, Oregon, USA.
Joseph
J
Ahn
Department of Digestive Diseases, Yale University, New Haven, Connecticut, USA.
Joseph K
JK
Lim
Gastroenterology/Hepatology Division, Virginia Commonwealth University, Richmond, Virginia, USA.
Hannah M
HM
Lee
Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA.
Anna S
AS
Lok
Division of Gastroenterology and Hepatology, Stanford University, Stanford, California, USA.
Mindie
M
Nguyen
Department of Medicine, NYU Langone, New York City, New York, USA.
Calvin Q
CQ
Pan
Division of Gastroenterology and Hepatology, Stanford University, Stanford, California, USA.
Ajitha
A
Mannalithara
Digestive Disease Center, University of Chicago, Chicago, Illinois, USA.
Helen
H
Te
Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
K Rajender
KR
Reddy
San Jose GI, San Jose, California, USA.
Huy
H
Trinh
NYU School of Medicine, New York City, New York, USA.
Danny
D
Chu
Department of Medicine, Cedars Sinai Medical Center, Los Angeles, California, USA.
Tram
T
Tran
Department of Gastroenterology and Hepatology, BIDMC, Boston, Massachusetts, USA.
Daryl
D
Lau
Leduc Medical Group, Fountain Valley, California, USA.
Truong-Sinh
TS
Leduc
Division of Gastroenterology, Mount Sinai Beth Israel, New York City, New York, USA.
Albert
A
Min
Woodholme Gastroenterology Associates, Pikeville, Maryland, USA.
Loc
L
Trong Le
Asian Pacific Liver Center, Los Angeles, California, USA.
Ho
H
Bae
Falls Church Family Practice, Falls Church, Virginia, USA.
Sang
S
Van Tran
Digestive Health Associates of Texas, Plano, Texas, USA.
Son
S
Do
Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA.
Hie-Won L
HW
Hann
San Francisco, California, USA.
Clifford
C
Wong
University of California, Los Angeles, Los Angeles, California, USA.
Steven
S
Han
Emory University, Atlanta, Georgia, USA.
Anjana
A
Pillai
NYU Langone, New York City, New York, USA.
James S
JS
Park
Emory University, Atlanta, Georgia, USA.
Myron
M
Tong
Loyola University, Maywood, Illinois, USA.
Steve
S
Scaglione
Asian Health Foundation, Philadelphia, Pennsylvania, USA.
Jocelyn
J
Woog
Division of Gastroenterology and Hepatology, Stanford University, Stanford, California, USA.
W Ray
WR
Kim
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology*; D015331:Cohort Studies; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000209:etiology; D008113:Liver Neoplasms / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014481:United States / Q000453:epidemiology; D055815:Young Adult
D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; C413685:entecavir; D006147:Guanine