Yao-Chun Hsu1, Terry Cheuk-Fung Yip2, Hsiu J Ho3, Vincent Wai-Sun Wong2, Yen-Tsung Huang4, Hashem B El-Serag5, Teng-Yu Lee6, Ming-Shiang Wu7, Jaw-Town Lin8, Grace Lai-Hung Wong9, Chun-Ying Wu10. 1. Big Data Research Center, School of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan; Division of Gastroenterology, Fu-Jen Catholic University Hospital, New Taipei, Taiwan; Division of Gastroenterology and Hepatology, E-Da Hospital, Kaohsiung, Taiwan; Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan. 2. Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong; Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Digestive Disease, Chinese University of Hong Kong, Hong Kong. 3. Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan. 4. Institute of Statistical Science, Academia Sinica, Taipei, Taiwan. 5. Section of Gastroenterology and Hepatology, Department of Medicine, Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, TX, USA. 6. Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Medicine, Chung Shan Medical University, Taichung, Taiwan. 7. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. 8. Big Data Research Center, School of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan; Division of Gastroenterology, Fu-Jen Catholic University Hospital, New Taipei, Taiwan. 9. Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong; Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Digestive Disease, Chinese University of Hong Kong, Hong Kong. Electronic address: wonglaihung@cuhk.edu.hk. 10. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan; Faculty of Medicine and Graduate Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Public Health, China Medical University, Taichung, Taiwan; National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan. Electronic address: chun@vghtc.gov.tw.
Abstract
BACKGROUND & AIMS: The risk of hepatocellular carcinoma (HCC) during antiviral therapy in patients with chronic hepatitis B (CHB) is inadequately predicted by the scores built from untreated patients. We aimed at developing and validating a risk score to predict HCC in patients with CHB on entecavir or tenofovir treatment. METHODS: This study analysed population-wide data from the healthcare databases in Taiwan and Hong Kong to identify patients with CHB continuously receiving entecavir or tenofovir. The development cohort included 23,851 patients from Taiwan; 596 (2.50%) of them developed HCC with a three-year cumulative incidence of 3.56% (95% CI 3.26-3.86%). The multivariable Cox proportional hazards model found that cirrhosis, age (cirrhosis and age interacted with each other), male sex, and diabetes mellitus were the risk determinants. These variables were weighted to develop the cirrhosis, age, male sex, and diabetes mellitus (CAMD) score ranging from 0 to 19 points. The score was externally validated in 19,321 patients from Hong Kong. RESULTS: The c indices for HCC in the development cohort were 0.83 (95% CI 0.81-0.84), 0.82 (95% CI 0.81-0.84), and 0.82 (95% CI 0.80-0.83) at the first, second, and third years of therapy, respectively. In the validation cohort, the c indices were 0.74 (95% CI 0.71-0.77), 0.75 (95% CI 0.73-0.78), and 0.75 (95% CI 0.72-0.77) during the first three years, and 0.76 (95% CI 0.74-0.78) and 0.76 (95% CI 0.74-0.77) in the extrapolated fourth and fifth years, respectively. The predicted and observed probabilities of HCC were calibrated in both cohorts. A score <8 and >13 points identified patients at distinctly low and high risks. CONCLUSIONS: The easily calculable CAMD score can predict HCC and may inform surveillance policy in patients with CHB during oral antiviral therapy. LAY SUMMARY: This study analyses population-wide data from the healthcare systems in Taiwan and Hong Kong to develop and validate a risk score that predicts hepatocellular carcinoma during oral antiviral therapy in patients with chronic hepatitis B. The easily calculable CAMD score requires only simple information (i.e. cirrhosis, age, male sex, and diabetes mellitus) at the baseline of treatment initiation. With a scoring range from 0 to 19 points, the CAMD score discriminates the risk of hepatocellular carcinoma with a concordance rate of around 75-80% during the first three years on therapy. The risk prediction can be extrapolated to five years on treatment with similar accuracy. Patients with a score <8 and >13 points were exposed to distinctly lower and higher risks, respectively.
BACKGROUND & AIMS: The risk of hepatocellular carcinoma (HCC) during antiviral therapy in patients with chronic hepatitis B (CHB) is inadequately predicted by the scores built from untreated patients. We aimed at developing and validating a risk score to predict HCC in patients with CHB on entecavir or tenofovir treatment. METHODS: This study analysed population-wide data from the healthcare databases in Taiwan and Hong Kong to identify patients with CHB continuously receiving entecavir or tenofovir. The development cohort included 23,851 patients from Taiwan; 596 (2.50%) of them developed HCC with a three-year cumulative incidence of 3.56% (95% CI 3.26-3.86%). The multivariable Cox proportional hazards model found that cirrhosis, age (cirrhosis and age interacted with each other), male sex, and diabetes mellitus were the risk determinants. These variables were weighted to develop the cirrhosis, age, male sex, and diabetes mellitus (CAMD) score ranging from 0 to 19 points. The score was externally validated in 19,321 patients from Hong Kong. RESULTS: The c indices for HCC in the development cohort were 0.83 (95% CI 0.81-0.84), 0.82 (95% CI 0.81-0.84), and 0.82 (95% CI 0.80-0.83) at the first, second, and third years of therapy, respectively. In the validation cohort, the c indices were 0.74 (95% CI 0.71-0.77), 0.75 (95% CI 0.73-0.78), and 0.75 (95% CI 0.72-0.77) during the first three years, and 0.76 (95% CI 0.74-0.78) and 0.76 (95% CI 0.74-0.77) in the extrapolated fourth and fifth years, respectively. The predicted and observed probabilities of HCC were calibrated in both cohorts. A score <8 and >13 points identified patients at distinctly low and high risks. CONCLUSIONS: The easily calculable CAMD score can predict HCC and may inform surveillance policy in patients with CHB during oral antiviral therapy. LAY SUMMARY: This study analyses population-wide data from the healthcare systems in Taiwan and Hong Kong to develop and validate a risk score that predicts hepatocellular carcinoma during oral antiviral therapy in patients with chronic hepatitis B. The easily calculable CAMD score requires only simple information (i.e. cirrhosis, age, male sex, and diabetes mellitus) at the baseline of treatment initiation. With a scoring range from 0 to 19 points, the CAMD score discriminates the risk of hepatocellular carcinoma with a concordance rate of around 75-80% during the first three years on therapy. The risk prediction can be extrapolated to five years on treatment with similar accuracy. Patients with a score <8 and >13 points were exposed to distinctly lower and higher risks, respectively.
Authors: Hye Won Lee; Hyun Woong Lee; Jae Seung Lee; Yun Ho Roh; Hyein Lee; Seung Up Kim; Jun Yong Park; Do Young Kim; Sang Hoon Ahn; Beom Kyung Kim Journal: J Hepatocell Carcinoma Date: 2021-05-25
Authors: 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-Gomez; Bettina E Hansen; Savvoula Savvidou; Anastasia Kourikou; John Vlachogiannakos; Kostas Galanis; Cihan Yurdaydin; Rafael Esteban; Harry L A Janssen; Thomas Berg; Pietro Lampertico Journal: JHEP Rep Date: 2021-04-20