Lower Observed Hepatocellular Carcinoma Incidence in Chronic Hepatitis B Patients Treated With Entecavir: Results of the ENUMERATE Study

Joseph Ahn, Joseph K. Lim, Hannah M. Lee, Anna S. Lok, Mindie Nguyen, Calvin Q. Pan, Ajitha Mannalithara, Helen Te, K. Rajender Reddy, Huy Trinh, Danny Chu, Tram Tran, Daryl Lau, Truong Sinh Leduc, Albert Min, Loc Trong Le, Ho Bae, Sang Van Tran, Son Do, Hie Won L HannClifford Wong, Steven Han, Anjana Pillai, James S. Park, Myron Tong, Steve Scaglione, Jocelyn Woog, W. Ray Kim

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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.

Original languageEnglish (US)
Pages (from-to)1297-1304
Number of pages8
JournalAmerican Journal of Gastroenterology
Volume111
Issue number9
DOIs
StatePublished - Sep 1 2016

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Chronic Hepatitis B
Hepatocellular Carcinoma
Incidence
Fibrosis
entecavir
Confidence Intervals
Hepatitis B e Antigens

ASJC Scopus subject areas

  • Medicine(all)
  • Gastroenterology

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Lower Observed Hepatocellular Carcinoma Incidence in Chronic Hepatitis B Patients Treated With Entecavir : Results of the ENUMERATE Study. / Ahn, Joseph; Lim, Joseph K.; Lee, Hannah M.; Lok, Anna S.; Nguyen, Mindie; Pan, Calvin Q.; Mannalithara, Ajitha; Te, Helen; Reddy, K. Rajender; Trinh, Huy; Chu, Danny; Tran, Tram; Lau, Daryl; Leduc, Truong Sinh; Min, Albert; Trong Le, Loc; Bae, Ho; Van Tran, Sang; Do, Son; Hann, Hie Won L; Wong, Clifford; Han, Steven; Pillai, Anjana; Park, James S.; Tong, Myron; Scaglione, Steve; Woog, Jocelyn; Kim, W. Ray.

In: American Journal of Gastroenterology, Vol. 111, No. 9, 01.09.2016, p. 1297-1304.

Research output: Contribution to journalArticle

Ahn, J, Lim, JK, Lee, HM, Lok, AS, Nguyen, M, Pan, CQ, Mannalithara, A, Te, H, Reddy, KR, Trinh, H, Chu, D, Tran, T, Lau, D, Leduc, TS, Min, A, Trong Le, L, Bae, H, Van Tran, S, Do, S, Hann, HWL, Wong, C, Han, S, Pillai, A, Park, JS, Tong, M, Scaglione, S, Woog, J & Kim, WR 2016, 'Lower Observed Hepatocellular Carcinoma Incidence in Chronic Hepatitis B Patients Treated With Entecavir: Results of the ENUMERATE Study', American Journal of Gastroenterology, vol. 111, no. 9, pp. 1297-1304. https://doi.org/10.1038/ajg.2016.257
Ahn, Joseph ; Lim, Joseph K. ; Lee, Hannah M. ; Lok, Anna S. ; Nguyen, Mindie ; Pan, Calvin Q. ; Mannalithara, Ajitha ; Te, Helen ; Reddy, K. Rajender ; Trinh, Huy ; Chu, Danny ; Tran, Tram ; Lau, Daryl ; Leduc, Truong Sinh ; Min, Albert ; Trong Le, Loc ; Bae, Ho ; Van Tran, Sang ; Do, Son ; Hann, Hie Won L ; Wong, Clifford ; Han, Steven ; Pillai, Anjana ; Park, James S. ; Tong, Myron ; Scaglione, Steve ; Woog, Jocelyn ; Kim, W. Ray. / Lower Observed Hepatocellular Carcinoma Incidence in Chronic Hepatitis B Patients Treated With Entecavir : Results of the ENUMERATE Study. In: American Journal of Gastroenterology. 2016 ; Vol. 111, No. 9. pp. 1297-1304.
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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.",
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T1 - Lower Observed Hepatocellular Carcinoma Incidence in Chronic Hepatitis B Patients Treated With Entecavir

T2 - Results of the ENUMERATE Study

AU - Ahn, Joseph

AU - Lim, Joseph K.

AU - Lee, Hannah M.

AU - Lok, Anna S.

AU - Nguyen, Mindie

AU - Pan, Calvin Q.

AU - Mannalithara, Ajitha

AU - Te, Helen

AU - Reddy, K. Rajender

AU - Trinh, Huy

AU - Chu, Danny

AU - Tran, Tram

AU - Lau, Daryl

AU - Leduc, Truong Sinh

AU - Min, Albert

AU - Trong Le, Loc

AU - Bae, Ho

AU - Van Tran, Sang

AU - Do, Son

AU - Hann, Hie Won L

AU - Wong, Clifford

AU - Han, Steven

AU - Pillai, Anjana

AU - Park, James S.

AU - Tong, Myron

AU - Scaglione, Steve

AU - Woog, Jocelyn

AU - Kim, W. Ray

PY - 2016/9/1

Y1 - 2016/9/1

N2 - 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.

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