Joseph Ahn1, Joseph K Lim2, Hannah M Lee3, Anna S Lok4, Mindie Nguyen5, Calvin Q Pan6, Ajitha Mannalithara5, Helen Te7, K Rajender Reddy8, Huy Trinh9, Danny Chu10, Tram Tran11, Daryl Lau12, Truong-Sinh Leduc13, Albert Min14, Loc Trong Le15, Ho Bae16, Sang Van Tran17, Son Do18, Hie-Won L Hann19, Clifford Wong20, Steven Han21, Anjana Pillai22, James S Park23, Myron Tong22, Steve Scaglione24, Jocelyn Woog25, W Ray Kim5. 1. Division of Gastroenterology and Hepatology, Oregon Health and Science University, Portland, Oregon, USA. 2. Department of Digestive Diseases, Yale University, New Haven, Connecticut, USA. 3. Gastroenterology/Hepatology Division, Virginia Commonwealth University, Richmond, Virginia, USA. 4. Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA. 5. Division of Gastroenterology and Hepatology, Stanford University, Stanford, California, USA. 6. Department of Medicine, NYU Langone, New York City, New York, USA. 7. Digestive Disease Center, University of Chicago, Chicago, Illinois, USA. 8. Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 9. San Jose GI, San Jose, California, USA. 10. NYU School of Medicine, New York City, New York, USA. 11. Department of Medicine, Cedars Sinai Medical Center, Los Angeles, California, USA. 12. Department of Gastroenterology and Hepatology, BIDMC, Boston, Massachusetts, USA. 13. Leduc Medical Group, Fountain Valley, California, USA. 14. Division of Gastroenterology, Mount Sinai Beth Israel, New York City, New York, USA. 15. Woodholme Gastroenterology Associates, Pikeville, Maryland, USA. 16. Asian Pacific Liver Center, Los Angeles, California, USA. 17. Falls Church Family Practice, Falls Church, Virginia, USA. 18. Digestive Health Associates of Texas, Plano, Texas, USA. 19. Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA. 20. San Francisco, California, USA. 21. University of California, Los Angeles, Los Angeles, California, USA. 22. Emory University, Atlanta, Georgia, USA. 23. NYU Langone, New York City, New York, USA. 24. Loyola University, Maywood, Illinois, USA. 25. Asian Health Foundation, Philadelphia, Pennsylvania, USA.
Abstract
OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Authors: W Ray Kim; Rohit Loomba; Thomas Berg; Raul E Aguilar Schall; Leland J Yee; Phillip V Dinh; John F Flaherty; Eduardo B Martins; Terry M Therneau; Ira Jacobson; Scott Fung; Selim Gurel; Maria Buti; Patrick Marcellin Journal: Cancer Date: 2015-07-15 Impact factor: 6.860
Authors: J Ahn; H M Lee; J K Lim; C Q Pan; M H Nguyen; W Ray Kim; A Mannalithara; H Trinh; D Chu; T Tran; A Min; S Do; H Te; K R Reddy; A S Lok Journal: Aliment Pharmacol Ther Date: 2015-10-28 Impact factor: 8.171
Authors: George Papatheodoridis; George Dalekos; Vana Sypsa; Cihan Yurdaydin; Maria Buti; John Goulis; Jose Luis Calleja; Heng Chi; Spilios Manolakopoulos; Giampaolo Mangia; Nikolaos Gatselis; Onur Keskin; Savvoula Savvidou; Juan de la Revilla; Bettina E Hansen; Ioannis Vlachogiannakos; Kostantinos Galanis; Ramazan Idilman; Massimo Colombo; Rafael Esteban; Harry L A Janssen; Pietro Lampertico Journal: J Hepatol Date: 2015-12-08 Impact factor: 25.083
Authors: George V Papatheodoridis; George N Dalekos; Cihan Yurdaydin; Maria Buti; John Goulis; Pauline Arends; Vana Sypsa; Spilios Manolakopoulos; Giampaolo Mangia; Nikolaos Gatselis; Onur Keskın; Savvoula Savvidou; Bettina E Hansen; Christos Papaioannou; Kostantinos Galanis; Ramazan Idilman; Massimo Colombo; Rafael Esteban; Harry L A Janssen; Pietro Lampertico Journal: J Hepatol Date: 2014-09-06 Impact factor: 25.083
Authors: Pauline Arends; Milan J Sonneveld; Roeland Zoutendijk; Ivana Carey; Ashley Brown; Massimo Fasano; David Mutimer; Katja Deterding; Jurriën G P Reijnders; Ye Oo; Jörg Petersen; Florian van Bömmel; Robert J de Knegt; Teresa Santantonio; Thomas Berg; Tania M Welzel; Heiner Wedemeyer; Maria Buti; Pierre Pradat; Fabien Zoulim; Bettina Hansen; Harry L A Janssen Journal: Gut Date: 2014-07-10 Impact factor: 23.059