Knowledge Graph Augmented Large Language Models for Next-Visit Disease Prediction

Abstract: Electronic health records (EHRs) support powerful clinical prediction models, but existing methods typically provide coarse, post hoc explanations that offer limited value for patient-level decision making. We introduce a knowledge graph (KG)-guided chain-of-thought (CoT) framework that generates clinically grounded and temporally consistent reasoning for visit-level disease prediction in MIMIC-III. ICD-9 codes are mapped to PrimeKG, from which disease-relevant nodes and multi-hop reasoning paths are extracted and used as scaffolds for CoT generation; only explanations whose conclusions match observed outcomes are retained. Lightweight LLaMA-3.1-Instruct-8B and Gemma-7B models are then fine-tuned on this supervision corpus. Across ten PrimeKG-mapped diseases and limited training cohorts (400 and 1000 cases), KG-guided models outperform strong classical baselines, achieving AUROC values of 0.66 to 0.70 and macro-AUPR values of 0.40 to 0.47. The models also transfer zero-shot to the CRADLE cohort, improving accuracy from approximately 0.40 to 0.51 up to 0.72 to 0.77. A blinded clinician evaluation shows consistent preference for KG-guided CoT explanations in clarity, relevance, and clinical correctness.