Personalized Antiviral Drug Selection in Patients With Chronic Hepatitis B Using a Machine Learning Model: A Multinational Study
Moon Haeng Hur, Min Kyung Park, Terry Cheuk‐Fung Yip, Chien‐Hung Chen, Hyung‐Chul Lee, Won‐Mook Choi, Seung Up Kim, Young‐Suk Lim, Soo Young Park, Grace Lai‐Hung Wong, Dong Hyun Sinn, Young‐Joo Jin, Sung Eun Kim, Cheng‐Yuan Peng, Hyun Phil Shin, Chi-Yi Chen, Hwi Young Kim, Han Ah Lee, Yeon Seok Seo, Dae Won Jun, Eileen L. Yoon, Joo Hyun Sohn, Sang Bong Ahn, Jae‐Jun Shim, Soung Won Jeong, Yong Kyun Cho, Hyoung Su Kim, Myoung‐jin Jang, Yoon Jun Kim, Jung‐Hwan Yoon, Jeong‐Hoon Lee
Abstract
INTRODUCTION: Tenofovir disoproxil fumarate (TDF) is reportedly superior or at least comparable to entecavir (ETV) for the prevention of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B; however, it has distinct long-term renal and bone toxicities. This study aimed to develop and validate a machine learning model (designated as Prediction of Liver cancer using Artificial intelligence-driven model for Network-antiviral Selection for hepatitis B [PLAN-S]) to predict an individualized risk of HCC during ETV or TDF therapy. METHODS: This multinational study included 13,970 patients with chronic hepatitis B. The derivation (n = 6,790), Korean validation (n = 4,543), and Hong Kong-Taiwan validation cohorts (n = 2,637) were established. Patients were classified as the TDF-superior group when a PLAN-S-predicted HCC risk under ETV treatment is greater than under TDF treatment, and the others were defined as the TDF-nonsuperior group. RESULTS: The PLAN-S model was derived using 8 variables and generated a c-index between 0.67 and 0.78 for each cohort. The TDF-superior group included a higher proportion of male patients and patients with cirrhosis than the TDF-nonsuperior group. In the derivation, Korean validation, and Hong Kong-Taiwan validation cohorts, 65.3%, 63.5%, and 76.4% of patients were classified as the TDF-superior group, respectively. In the TDF-superior group of each cohort, TDF was associated with a significantly lower risk of HCC than ETV (hazard ratio = 0.60-0.73, all P < 0.05). In the TDF-nonsuperior group, however, there was no significant difference between the 2 drugs (hazard ratio = 1.16-1.29, all P > 0.1). DISCUSSION: Considering the individual HCC risk predicted by PLAN-S and the potential TDF-related toxicities, TDF and ETV treatment may be recommended for the TDF-superior and TDF-nonsuperior groups, respectively.