Post-transplant hepatocellular carcinoma score: A simple point-based risk stratification system for 5-year mortality after liver transplantation in patients with hepatocellular carcinoma and explant pathology beyond Milan criteria.

Abstract

Background: Patients undergoing liver transplantation for hepatocellular carcinoma beyond the Milan criteria represent an expanding population with heterogeneous outcomes. We developed and validated a point-based score (post-transplant hepatocellular carcinoma score) to stratify 5-year mortality risk using readily available clinical and pathologic variables analyzed via machine learning.

Methods: We analyzed hepatocellular carcinoma liver transplant recipients from the United Network for Organ Sharing database (2012-2019) with determinable 5-year outcomes whose explant pathology exceeded Milan criteria. A gradient-boosting classifier identified key predictors of mortality. Based on feature importance, we developed a 0-5 point score using the post-transplant-hepatocellular carcinoma components. Risk categories were low (score 0), moderate (score 1-2), and high (score 3-5).

Results: Among 2,952 patients, 812 (27.5%) died within 5 years of transplantation. The post-transplant hepatocellular carcinoma score stratified patients into 3 risk groups, with 5-year survival of 82.7% (low), 72.2% (moderate), and 50.2% (high). Survival decreased monotonically with score, from 82.7% at score 0 to 39.0% at score 4. In the temporally independent 2019 validation cohort, the score demonstrated an area under the curve of 0.619 (95% confidence interval, 0.554-0.678), with 5-year survival of 84.0%, 72.2%, and 47.1% in the low-, moderate-, and high-risk groups, respectively. The score performed similarly to the Risk Estimation of Tumor Recurrence After Transplant score (area under the curve, 0.619 vs 0.629; P = .72).

Conclusion: The post-transplant hepatocellular carcinoma score is a simple, validated tool for stratifying 5-year mortality risk in hepatocellular carcinoma transplant recipients beyond the Milan criteria and may assist in surveillance planning, patient counseling, and clinical decision-making pending external validation.