Background/Aims This study aimed to develop and validate a risk prediction model for the development of hepatocellular carcinoma (HCC) in treatment-naïve patients receiving oral antiviral treatment for chronic hepatitis B (CHB).
Methods We investigated 2,061 Korean treatment-naïve patients with CHB treated with entecavir as an initial therapy. A risk score model for HCC development was developed based on multivariable Cox regression model in a single center (n=990) and was validated using the time-dependent area under the receiver operating characteristic curve (AUROC) in three other centers (n=1,071). The difference of HCC development among risk groups (low, intermediate, and high) categorized by risk score was also investigated.
Results The cumulative incidence rates of HCC at 5 years were 11.2% and 8.9% in the testing and validation cohorts, respectively. HCC-Risk Estimating Score in CHB patients Under Entecavir (HCC-RESCUE) is formulated as (age+15×gender [female=0 / male=1]+23×cirrhosis [absence=0 / presence=1]). The AUROCs at 1 year, 3 years, and 5 years were 0.82, 0.81, and 0.81, respectively, in the validation cohort. A significant difference of HCC development in each risk group was determined by the 5-year HCC risk score in the validation cohort (low risk group, 2.1%; intermediate risk group, 9.3%; high risk group, 41.2%, p<0.001).
Conclusions The study presents a new risk score model with a good ability to predict HCC development and determine high risk patients for HCC development consisting of readily available clinical factors in treatment-naïve CHB patients receiving entecavir.
Citations
Citations to this article as recorded by
Risk Scores for Stratifying Hepatocellular Carcinoma and Optimizing Surveillance Strategies Yu-Ping Chang, Yun-Chu Chen, Chen-Hua Liu Cancers.2026; 18(1): 158. CrossRef
AGA Clinical Practice Update on Risk Stratification and Emerging Surveillance Strategies for Hepatocellular Carcinoma: Expert Review Nicole E. Rich, Augusto Villanueva, Jorge A. Marrero, Fasiha Kanwal Gastroenterology.2026; 170(7): 1606. CrossRef
A systematic review and time-specific meta-analysis of hepatocellular carcinoma risk prediction models Jingru Huang, Wenwen Jiang, Chaoqiang Jiang, Weisen Zhang, Feng Zhu, Jing Pan, Tai Hing Lam Oncology and Translational Medicine.2026;[Epub] CrossRef
Surveillance of patients at risk of liver cancer: Expert opinions Terry Cheuk-Fung Yip, Hamish Innes, Grace Lai-Hung Wong, Peter Jepsen Journal of Hepatology.2026;[Epub] CrossRef
Behaviour‐Based Predictive Scores of Hepatocellular Carcinoma in People With Chronic Hepatitis B (ANRS CO22 HEPATHER) Clémence Ramier, Camelia Protopopescu, Vincent Di Beo, Lucia Parlati, Fabienne Marcellin, Fabrice Carrat, Tarik Asselah, Marc Bourlière, Patrizia Carrieri Liver International.2025;[Epub] CrossRef
Validation Study of Scores Predicting Hepatocellular Carcinoma Risk in Chronic Hepatitis B Patients Treated With Nucleos(t)ide Analogues Jun Inoue, Shinichiro Minami, Kazumichi Abe, Mami Kida, Hiroaki Haga, Chikara Iino, Hiroshi Numao, Hidekatsu Kuroda, Masashi Ninomiya, Mio Tsuruoka, Kosuke Sato, Masazumi Onuki, Satoko Sawahashi, Keishi Ouchi, Kengo Watanabe, Takehiro Akahane, Tomoo Kobay Journal of Viral Hepatitis.2025;[Epub] CrossRef
A Review of Risk Prediction Model for Hepatocellular Carcinoma in Chronic Hepatitis B Jiwon Yang, Mark D. Muthiah, Won-Mook Choi Current Hepatology Reports.2025;[Epub] CrossRef
MR elastography-based prediction of development of hepatocellular carcinoma in patients with chronic hepatitis B with sustained virological response Haimei Chen, Jie Zhu, Jinhui Zhou, Ziying Yin, Jun Chen, Sudhakar K. Venkatesh, Meng Yin, Richard L. Ehman, Jin Wang European Radiology.2025; 35(12): 8032. CrossRef
Current and new strategies for hepatocellular carcinoma surveillance Natchaya Polpichai, Chongkonrat Maneenil, Pojsakorn Danpanichkul, Chitchai Rattananukrom, Ashok Choudhury, Yu Jun Wong, Pimsiri Sripongpun, Suthat Liangpunsakul, Apichat Kaewdech Gastroenterology Report.2025;[Epub] CrossRef
Score-based prediction model for female hepatocellular carcinoma surveillance in asymptotic HBsAg carriers: a multicenter cohort study in China Mengdi Cao, Maomao Cao, Changfa Xia, Fan Yang, Xinxin Yan, Siyi He, Shaoli Zhang, Yi Teng, Qianru Li, Nuopei Tan, Jiachen Wang, Chunfeng Qu, Wanqing Chen Journal of the National Cancer Center.2025; 5(5): 493. CrossRef
Dynamic changes in liver stiffness measurement by 2D shear-wave elastography predict hepatocellular carcinoma in patients with chronic hepatitis B and well-controlled viremia: a retrospective study Nana Wang, Yuankai Wu, Mingyue Xiao, Yusheng Jie, Jinfen Wang, Manli Wu, Jiaxin Chen, Liuping Sha, Zhongzhen Su, Yutian Chong, Lili Wu BMC Gastroenterology.2025;[Epub] CrossRef
Liver Stiffness Measurements After Oral Antivirals Effectively Predict the Risk of HCC in Patients With Chronic Hepatitis C Yu Rim Lee, Hyun Young Woo, Young Oh. Kweon, Won Young Tak, Se Young Jang, Jung Gil Park, Min Kyu Kang, Jeong Eun Song, Byoung Kuk Jang, Changhyeong Lee, Byung Seok Kim, Jae Seok Hwang, Woo Jin Chung, Jeong Heo, Nae‐Yun Heo, Seung Ha Park, Jun Sik Yoon, J Journal of Gastroenterology and Hepatology.2025; 40(10): 2568. CrossRef
Early screening for liver cancer must be performed Zi-Han Liu, Wen-Jun Wang, Shuang-Suo Dang World Journal of Hepatology.2025;[Epub] CrossRef
A prediction nomogram for hepatitis B virus-associated hepatocellular carcinoma Yijin Zhang, Gang Wan, Hongjie Li, Lili Gao, Nan Liu, Ping Gao, Yaping Liu, Xuesong Gao, Xuefei Duan Scandinavian Journal of Gastroenterology.2024; 59(1): 70. CrossRef
A Liver Stiffness–Based Etiology-Independent Machine Learning Algorithm to Predict Hepatocellular Carcinoma Huapeng Lin, Guanlin Li, Adèle Delamarre, Sang Hoon Ahn, Xinrong Zhang, Beom Kyung Kim, Lilian Yan Liang, Hye Won Lee, Grace Lai-Hung Wong, Pong-Chi Yuen, Henry Lik-Yuen Chan, Stephen Lam Chan, Vincent Wai-Sun Wong, Victor de Lédinghen, Seung Up Kim, Terr Clinical Gastroenterology and Hepatology.2024; 22(3): 602. CrossRef
Applicability of Risk Scores to an Indian Cohort of Hepatitis B-Related Hepatocellular Carcinoma Patients Gautam Ray Journal of Clinical and Experimental Hepatology.2024; 14(4): 101370. CrossRef
Reduced Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Receiving Long-Term Besifovir Therapy Hyung Joon Yim, Seong Hee Kang, Young Kul Jung, Sang Hoon Ahn, Won Kim, Jin Mo Yang, Jae Young Jang, Yong Oh Kweon, Yong Kyun Cho, Yoon Jun Kim, Gun Young Hong, Dong Joon Kim, Joo Hyun Sohn, Jin Woo Lee, Sung Jae Park, Sun Young Yim, Jin Kyung Park, Soon Cancers.2024; 16(5): 887. CrossRef
Prognostic significance of dynamic changes in liver stiffness measurement in patients with chronic hepatitis B and compensated advanced chronic liver disease Hongsheng Yu, Yinan Huang, Mingkai Li, Hao Jiang, Bilan Yang, Xiaoli Xi, Abdukyamu Smayi, Bin Wu, Yidong Yang Journal of Gastroenterology and Hepatology.2024; 39(10): 2169. CrossRef
Disease modifiers and novel markers in hepatitis B virus-related hepatocellular carcinoma Lung-Yi Mak Journal of Liver Cancer.2024; 24(2): 145. CrossRef
Risk predictive model for the development of hepatocellular carcinoma before initiating long‐term antiviral therapy in patients with chronic hepatitis B virus infection Junjie Chen, Tienan Feng, Qi Xu, Xiaoqi Yu, Yue Han, Demin Yu, Qiming Gong, Yuan Xue, Xinxin Zhang Journal of Medical Virology.2024;[Epub] CrossRef
Risk stratification and early detection biomarkers for precision HCC screening Yi‐Te Lee, Naoto Fujiwara, Ju Dong Yang, Yujin Hoshida Hepatology.2023; 78(1): 319. CrossRef
Factors associated with persistent positive in HBV DNA level in patients with chronic Hepatitis B receiving entecavir treatment Jun Li, Xiao-Qin Dong, Li-Hua Cao, Zhan-Qing Zhang, Wei-Feng Zhao, Qing-Hua Shang, Da-Zhi Zhang, An-Lin Ma, Qing Xie, Hong-Lian Gui, Guo Zhang, Ying-Xia Liu, Jia Shang, Shi-Bin Xie, Yi-Qi Liu, Chi Zhang, Gui-Qiang Wang, Hong Zhao Frontiers in Cellular and Infection Microbiology.2023;[Epub] CrossRef
HCC prediction models in chronic hepatitis B patients receiving entecavir or tenofovir: a systematic review and meta-analysis Xiaolan Xu, Lushun Jiang, Yifan Zeng, Liya Pan, Zhuoqi Lou, Bing Ruan Virology Journal.2023;[Epub] CrossRef
Prediction model of hepatitis B virus-related hepatocellular carcinoma in patients receiving antiviral therapy Beom Kyung Kim, Sang Hoon Ahn Journal of the Formosan Medical Association.2023; 122(12): 1238. CrossRef
Development of hepatocellular carcinoma in treated and untreated patients with chronic hepatitis B virus infection Chih-Lin Lin, Jia-Horng Kao Clinical and Molecular Hepatology.2023; 29(3): 605. CrossRef
A machine learning model for predicting hepatocellular carcinoma risk in patients with chronic hepatitis B Hye Won Lee, Hwiyoung Kim, Taeyun Park, Soo Young Park, Young Eun Chon, Yeon Seok Seo, Jae Seung Lee, Jun Yong park, Do Young Kim, Sang Hoon Ahn, Beom Kyung Kim, Seung Up Kim Liver International.2023; 43(8): 1813. CrossRef
Improving prediction of hepatocellular carcinoma in chronic hepatitis B by machine learning: Productive relationship of medicine with computer science Terry C. F. Yip, Cihan Yurdaydin Liver International.2023; 43(8): 1626. CrossRef
Comparative performance of risk prediction models for hepatitis B-related hepatocellular carcinoma in the United States Hyun-seok Kim, Xian Yu, Jennifer Kramer, Aaron P. Thrift, Pete Richardson, Yao-Chun Hsu, Avegail Flores, Hashem B. El-Serag, Fasiha Kanwal Journal of Hepatology.2022; 76(2): 294. CrossRef
An artificial intelligence model to predict hepatocellular carcinoma risk in Korean and Caucasian patients with chronic hepatitis B Hwi Young Kim, Pietro Lampertico, Joon Yeul Nam, Hyung-Chul Lee, Seung Up Kim, Dong Hyun Sinn, Yeon Seok Seo, Han Ah Lee, Soo Young Park, Young-Suk Lim, Eun Sun Jang, Eileen L. Yoon, Hyoung Su Kim, Sung Eun Kim, Sang Bong Ahn, Jae-Jun Shim, Soung Won Jeon Journal of Hepatology.2022; 76(2): 311. CrossRef
An MRI-Based Radiomic Model for Individualized Prediction of Hepatocellular Carcinoma in Patients With Hepatitis B Virus-Related Cirrhosis Yichen Wei, Jie Gong, Xin He, Bo Liu, Tiejun Liu, Shuohui Yang, Zhipeng Zhou, Lingyan Liang, Songhua Zhan, Ziqiang Xia, Gaoxiong Duan, Bin Lin, Qiuli Han, Shasha Li, Wei Qin, Perry J. Pickhardt, Demao Deng Frontiers in Oncology.2022;[Epub] CrossRef
Risk of hepatocellular carcinoma in antiviral treatment-naïve chronic hepatitis B patients treated with entecavir or tenofovir disoproxil fumarate: a network meta-analysis Ze-Hong Huang, Gui-Yang Lu, Ling-Xian Qiu, Guo-Hua Zhong, Yue Huang, Xing-Mei Yao, Xiao-Hui Liu, Shou-Jie Huang, Ting Wu, Quan Yuan, Ying-Bin Wang, Ying-Ying Su, Jun Zhang, Ning-Shao Xia BMC Cancer.2022;[Epub] CrossRef
Hepatitis B Virus-Associated Hepatocellular Carcinoma Giacomo Emanuele Maria Rizzo, Giuseppe Cabibbo, Antonio Craxì Viruses.2022; 14(5): 986. CrossRef
External Validation of LCR1-LCR2, a Multivariable Hepatocellular Carcinoma Risk Calculator, in a Multiethnic Cohort of Patients With Chronic Hepatitis B Thierry Poynard, Jean Marc Lacombe, Olivier Deckmyn, Valentina Peta, Sepideh Akhavan, Fabien Zoulim, Victor de Ledinghen, Didier Samuel, Philippe Mathurin, Vlad Ratziu, Dominique Thabut, Chantal Housset, Hélène Fontaine, Stanislas Pol, Fabrice Carrat Gastro Hep Advances.2022; 1(4): 604. CrossRef
The best predictive model for hepatocellular carcinoma in patients with chronic hepatitis B infection Jung Hwan Yu, Soon Gu Cho, Young-Joo Jin, Jin-Woo Lee Clinical and Molecular Hepatology.2022; 28(3): 351. CrossRef
Effect of entecavir and tenofovir disoproxil fumarate on hepatocellular carcinoma in subjects with chronic hepatitis B: a meta-analysis Sara M. Tony, Mohamed E. A. Shaaban, Ahmed I. M. Mohamed, Mohamed E. A. Abdelrahim Beni-Suef University Journal of Basic and Applied Sciences.2022;[Epub] CrossRef
A Mac-2 Binding Protein Glycosylation Isomer-Based Risk Model Predicts Hepatocellular Carcinoma in HBV-Related Cirrhotic Patients on Antiviral Therapy Chien-Hung Chen, Tsung-Hui Hu, Jing-Houng Wang, Hsueh-Chou Lai, Chao-Hung Hung, Sheng-Nan Lu, Cheng-Yuan Peng Cancers.2022; 14(20): 5063. CrossRef
Suboptimal Performance of Hepatocellular Carcinoma Prediction Models in Patients with Hepatitis B Virus-Related Cirrhosis Jae Lee, Tae Lim, Hye Lee, Seung Kim, Jun Park, Do Kim, Sang Ahn, Hyun Lee, Jung Lee, Ja Kim, In Min, Beom Kim Diagnostics.2022; 13(1): 3. CrossRef
Validation of risk prediction scores for hepatocellular carcinoma in patients with chronic hepatitis B treated with entecavir or tenofovir Jin Won Chang, Jae Seung Lee, Hye Won Lee, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Yeon Seok Seo, Han Ah Lee, Mi Na Kim, Yu Rim Lee, Seong Gyu Hwang, Kyu Sung Rim, Soon Ho Um, Won Young Tak, Young Oh Kweon, Soo Young Park, Seung Up Kim Journal of Viral Hepatitis.2021; 28(1): 95. CrossRef
Stratification of Hepatocellular Carcinoma Risk Following HCV Eradication or HBV Control Pierre Nahon, Erwan Vo Quang, Nathalie Ganne-Carrié Journal of Clinical Medicine.2021; 10(2): 353. CrossRef
Screening for Hepatocellular Carcinoma in Chronic Hepatitis B: An Update James Lok, Kosh Agarwal Viruses.2021; 13(7): 1333. CrossRef
Surveillance for hepatocellular carcinoma in chronic viral hepatitis: Is it time to personalize it? Coskun Ozer Demirtas, Maurizia Rossana Brunetto World Journal of Gastroenterology.2021; 27(33): 5536. CrossRef
Prediction models for development of hepatocellular carcinoma in chronic hepatitis B patients Jiang Guo, Xue-Song Gao World Journal of Clinical Cases.2021; 9(14): 3238. CrossRef
Validation of the HCC‐RESCUE score to predict hepatocellular carcinoma risk in Caucasian chronic hepatitis B patients under entecavir or tenofovir therapy Fatih Güzelbulut, Pınar Gökçen, Güray Can, Gupse Adalı, Ayça Gökçen Değirmenci Saltürk, Özgür Bahadır, Kamil Özdil, Hamdi Levent Doğanay Journal of Viral Hepatitis.2021; 28(5): 826. CrossRef
Predictive performance of newer Asian hepatocellular carcinoma risk scores in treated Caucasians with chronic hepatitis B George V. Papatheodoridis, George N. Dalekos, Ramazan Idilman, Vana Sypsa, Florian Van Boemmel, Maria Buti, Jose Luis Calleja, John Goulis, Spilios Manolakopoulos, Alessandro Loglio, Margarita Papatheodoridi, Nikolaos Gatselis, Rhea Veelken, Marta Lopez-G JHEP Reports.2021; 3(3): 100290. CrossRef
Screening for Hepatocellular Carcinoma in Patients with Hepatitis B Yashasavi Sachar, Mayur Brahmania, Renumathy Dhanasekaran, Stephen E. Congly Viruses.2021; 13(7): 1318. CrossRef
Application of Risk Scores for Hepatocellular Carcinoma in Patients with Chronic Hepatitis B: Current Status and Future Perspective Yao-Chun Hsu, Cheng-Hao Tseng, Yen-Tsung Huang, Hwai-I Yang Seminars in Liver Disease.2021; 41(03): 285. CrossRef
Validation of the CAMD Score in Patients With Chronic Hepatitis B Virus Infection Receiving Antiviral Therapy Seung Up Kim, Yeon Seok Seo, Han Ah Lee, Mi Na Kim, Eun Hwa Kim, Ha Yan Kim, Yu Rim Lee, Hye Won Lee, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han, Seong Gyu Hwang, Kyu Sung Rim, Soon Ho Um, Won Young Tak, Young Oh Kweon, Beom Kyung Kim, Soo Clinical Gastroenterology and Hepatology.2020; 18(3): 693. CrossRef
Clinical utility of hepatocellular carcinoma risk scores in chronic hepatitis B Thodoris Voulgaris, Margarita Papatheodoridi, Pietro Lampertico, George V. Papatheodoridis Liver International.2020; 40(3): 484. CrossRef
Nucleos(t)ide Analogues for Reducing Hepatocellular Carcinoma in Chronic Hepatitis B Patients: A Systematic Review and Meta-Analysis Xinhui Wang, Xiaoli Liu, Zhibo Dang, Lihua Yu, Yuyong Jiang, Xianbo Wang, Zhiyun Yan Gut and Liver.2020; 14(2): 232. CrossRef
Magnitude of and prediction for risk of hepatocellular carcinoma in patients with chronic hepatitis B taking entecavir or tenofovir therapy: A systematic review Cheng‐Hao Tseng, Chao‐Ming Tseng, Jia‐Ling Wu, Yao‐Chun Hsu, Hashem B. El-Serag Journal of Gastroenterology and Hepatology.2020; 35(10): 1684. CrossRef
Nucleos(t)ide analogues and Hepatitis B virus-related hepatocellular carcinoma: A literature review Mohamed A Abd El Aziz, Rodolfo Sacco, Antonio Facciorusso Antiviral Chemistry and Chemotherapy.2020; 28: 204020662092133. CrossRef
Obstacles and opportunities in the prevention and treatment of HBV-related hepatocellular carcinoma Yong Liao Genes & Diseases.2020; 7(3): 291. CrossRef
Deep learning model for prediction of hepatocellular carcinoma in patients with HBV-related cirrhosis on antiviral therapy Joon Yeul Nam, Dong Hyun Sinn, Junho Bae, Eun Sun Jang, Jin-Wook Kim, Sook-Hyang Jeong JHEP Reports.2020; 2(6): 100175. CrossRef
Risk Scores for Hepatocellular Carcinoma in Chronic Hepatitis B: A Promise for Precision Medicine George V. Papatheodoridis, Thodoris Voulgaris, Margarita Papatheodoridi, W. Ray Kim Hepatology.2020; 72(6): 2197. CrossRef
Risk factors and prevention of hepatocellular carcinoma in the era of precision medicine Naoto Fujiwara, Scott L. Friedman, Nicolas Goossens, Yujin Hoshida Journal of Hepatology.2018; 68(3): 526. CrossRef
Development of a scoring system to predict hepatocellular carcinoma in Asians on antivirals for chronic hepatitis B Yao-Chun Hsu, Terry Cheuk-Fung Yip, Hsiu J. Ho, Vincent Wai-Sun Wong, Yen-Tsung Huang, Hashem B. El-Serag, Teng-Yu Lee, Ming-Shiang Wu, Jaw-Town Lin, Grace Lai-Hung Wong, Chun-Ying Wu Journal of Hepatology.2018; 69(2): 278. CrossRef
Effect of Metabolic Syndrome on the Clinical Outcomes of Chronic Hepatitis B Patients with Nucleos(t)ide Analogues Treatment Nam Hee Kim, Yong Kyun Cho, Byung Ik Kim, Hong Joo Kim Digestive Diseases and Sciences.2018; 63(10): 2792. CrossRef
Modified PAGE-B score predicts the risk of hepatocellular carcinoma in Asians with chronic hepatitis B on antiviral therapy Ji Hyun Kim, Young Don Kim, Minjong Lee, Baek Gyu Jun, Tae Suk Kim, Ki Tae Suk, Seong Hee Kang, Moon Young Kim, Gab Jin Cheon, Dong Joon Kim, Soon Koo Baik, Dae Hee Choi Journal of Hepatology.2018; 69(5): 1066. CrossRef
Additional role of liver stiffness measurement in stratifying residual hepatocellular carcinoma risk predicted by serum biomarkers in chronic hepatitis B patients under antiviral therapy Byeong G. Song, Dong H. Sinn, Sangah Chi, Kyunga Kim, Wonseok Kang, Geum-Youn Gwak, Yong-Han Paik, Moon S. Choi, Joon H. Lee, Kwang C. Koh, Seung W. Paik European Journal of Gastroenterology & Hepatology.2018; 30(12): 1447. CrossRef
Development of a nomogram for screening of hepatitis B virus-associated hepatocellular carcinoma Jung Wha Chung, Eun Sun Jang, Jaihwan Kim, Sook-Hyang Jeong, Nayoung Kim, Dong Ho Lee, Kyung Ho Lee, Jin-Wook Kim Oncotarget.2017; 8(63): 106499. CrossRef
First
Prev
