Hur MH, Yip TC, Kim SU, Lee HW, Lee HA, Lee HC, Wong GL, Wong VW, Park JY, Ahn SH, Kim BK, Kim HY, Seo YS, Shin H, Park J, Ko Y, Park Y, Lee YB, Yu SJ, Lee SH, Kim YJ, Yoon JH, and Lee JH
Background & Aims: The risk of hepatocellular carcinoma (HCC) and hepatic decompensation persists after hepatitis B surface antigen (HBsAg) seroclearance. This study aimed to develop and validate a machine learning model to predict the risk of liver-related outcomes (LROs) following HBsAg seroclearance., Methods: A total of 4,787 consecutive patients who achieved HBsAg seroclearance between 2000 and 2022 were enrolled from 6 centers in South Korea and a territory-wide database in Hong Kong, comprising the training (n=944), internal validation (n=1,102), and external validation (n=2,741) cohorts. Three machine learning-based models were developed and compared in each cohort. The primary outcome was the development of any LRO, including HCC, decompensation, and liver-related death., Results: During a median follow-up of 55.2 (interquartile range=30.1-92.3) months, 123 LROs were confirmed (1.1%/person-year) in the Korean cohort. A model with the best predictive performance in the training cohort was selected as the final model (designated as PLAN-B-CURE), which was constructed using a gradient boosting algorithm and 7 variables (age, sex, diabetes, alcohol consumption, cirrhosis, albumin, and platelet count). Compared to previous HCC prediction models, PLAN-B-CURE showed significantly superior accuracy in the training cohort (c-index: 0.82 vs. 0.63-0.70, all P<0.001; area under the receiver operating characteristic curve: 0.86 vs. 0.62-0.72, all P<0.01; area under the precision-recall curve: 0.53 vs. 0.13-0.29, all P<0.01). PLAN-B-CURE showed a reliable calibration function (Hosmer-Lemeshow test P>0.05) and these results were reproduced in the internal and external validation cohorts., Conclusion: This novel machine learning model consisting of 7 variables provides reliable risk prediction of LRO after HBsAg seroclearance that can be used for personalized surveillance., Competing Interests: Declaration of Competing Interest Moon Haeng Hur: Nothing to declare; Terry Cheuk-Fung Yip: Terry Yip has served as an advisory committee member and a speaker for Gilead Sciences; Seung Up Kim: Nothing to declare; Hyun Woong Lee: Nothing to declare; Han Ah Lee: Nothing to declare; Hyung-Chul Lee: Nothing to declare; Grace Lai-Hung Wong: Grace Wong has served as an advisory committee member for AstraZeneca, Gilead Sciences and Janssen, and as a speaker for Abbott, AbbVie, Ascletis, Bristol-Myers Squibb, Echosens, Gilead Sciences, Janssen, and Roche. She has also received a research grant from Gilead Sciences; Vincent Wai-Sun Wong: Vincent Wong has served as a consultant or advisory committee member for AbbVie, Boehringer Ingelheim, Echosens, Intercept, Inventiva, Novo Nordisk, Pfizer, and TARGET PharmaSolutions; and a speaker for Abbott, AbbVie, Gilead Sciences, and Novo Nordisk. He has received a research grant from Gilead Sciences, and is a cofounder of Illuminatio Medical Technology Limited; Jun Yong Park: Nothing to declare; Sang Hoon Ahn: Nothing to declare; Beom Kyung Kim: Nothing to declare; Hwi Young Kim: Nothing to declare; Yeon Seok Seo: Nothing to declare; Hyunjae Shin: Nothing to declare; Jeayeon Park: Nothing to declare; Yunmi Ko: Nothing to declare; Youngsu Park: Nothing to declare; Yun Bin Lee: Yun Bin Lee receives research grants from Samjin Pharmaceuticals and Yuhan Pharmaceuticals; Su Jong Yu: Su Jong Yu receives research grants from Yuhan Pharmaceuticals and Daewoong Pharmaceuticals; Sang Hyub Lee: Nothing to disclose; Yoon Jun Kim: Yoon Jun Kim receives research grants from BTG, Boston Scientific, AstraZeneca, Gilead Sciences, Samjin, BL&H, and Bayer, and lecture fees from Roche, Abbvie, Eisai, Boston Scientific, BMS, BTG, Bayer, MSD, Novo Nordisk, Green Cross Cell, Boehringer Ingelheim, and Gilead Sciences; Jung-Hwan Yoon: Jung-Hwan Yoon receives research grants from Bayer, Daewoong Pharmaceutical, and Bukwang Pharmaceutical; Jeong-Hoon Lee: Jeong-Hoon Lee receives research grants from Yuhan Pharmaceuticals and GreenCross Cell, and lecture fees from GreenCross Cell, Daewoong Pharmaceuticals, and Gilead Korea., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)