Development and validation of a preoperative risk prediction model for severe complications and very early recurrence after liver resection for hepatocellular carcinoma

Introduction: We sought to develop and externally validate a preoperative model for predicting the risk of severe complications and very early recurrence after liver resection for hepatocellular carcinoma. Methods: Patients who underwent curative-intent hepatectomy for hepatocellular carcinoma between 2000 and 2023 were identified using a multi-institutional international database. Preoperative characteristics were assessed in relation to severe complications (defined as complications with a Clavien-Dindo classification III or greater) and very early recurrence (recurrence within 6 months after surgery) using multivariable analysis. Predictive models for severe complications and very early recurrence were developed and externally validated. Results: Among 969 patients, 97 patients (10.0%) experienced severe complications, and 116 patients (12.0%) developed very early recurrence. On multivariable analysis, American Society of Anesthesiologists class >2 and greater albumin-bilirubin score were associated with severe complications. Meanwhile, a greater albumin-bilirubin score and higher tumor burden score were associated with very early recurrence. A predictive model for very early recurrence was able to stratify patients relative to their risk for recurrence: low-risk (6-month recurrence-free survival, 94.1%), medium-risk (6-month recurrence-free survival, 86.0%), and high-risk (6-month recurrence-free survival, 67.1%). A total of 74 patients (7.6%) had an unfavorable risk profile (severe complication risk ≥30% and high-risk for very early recurrence). The discriminative accuracy of the severe complications (training: area under the curve, 0.69; external validation: area under the curve, 0.80) and very early recurrence (training: C-index: 0.65; external validation: C-index: 0.71) models were favorable (see online calculator: https://junkawashima.shinyapps.io/HCC_comp_VER/). Conclusion: An easy-to-use online calculator stratified patients relative to short- and long-term risks, identifying a subset of patients at a high risk of severe complications and very early recurrence who were unlikely to benefit from surgical resection.