Acute Graft-Versus-Host Disease After Orthotopic Liver Transplantation: Predicting This Rare Complication Using Machine Learning

Acute graft-versus-host disease (GVHD) is a rare complication after orthotopic liver transplantation (OLT) that carries high mortality. We hypothesized that machine-learning algorithms to predict rare events would identify patients at high risk for developing GVHD. To develop a predictive model, we retrospectively evaluated the clinical features of 1938 donor-recipient pairs at the time they underwent OLT at our center; 19 (1.0%) of these recipients developed GVHD. This population was divided into training (70%) and test (30%) sets. A total of 7 machine-learning classification algorithms were built based on the training data set to identify patients at high risk for GVHD. The C5.0, heterogeneous ensemble, and generalized gradient boosting machine (GGBM) algorithms predicted that 21% to 28% of the recipients in the test data set were at high risk for developing GVHD, with an area under the receiver operating characteristic curve (AUROC) of 0.83 to 0.86. The 7 algorithms were then evaluated in a validation data set of 75 more recent donor-recipient pairs who underwent OLT at our center; 2 of these recipients developed GVHD. The logistic regression, heterogeneous ensemble, and GGBM algorithms predicted that 9% to 11% of the validation recipients were at high risk for developing GVHD, with an AUROC of 0.93 to 0.96 that included the 2 recipients who developed GVHD. In conclusion, we present a practical model that can identify patients at high risk for GVHD who may warrant additional monitoring with peripheral blood chimerism testing.