Forecasting Waitlist Trajectories for Patients With Metabolic Dysfunction–Associated Steatohepatitis Cirrhosis: A Neural Network Competing Risk Analysis

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Background: Metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis is a leading indication for liver transplantation (LT). Patients with MASH cirrhosis are complex and often have extensive comorbidities. The current model for end-stage liver disease (MELD)-based liver allocation system has suboptimal concordance in predicting waitlist mortality for patients with MASH cirrhosis. Furthermore, it does not capture the competing outcomes of death and LT on the liver transplant waitlist. Objective: A competing risk analysis using deep learning was conducted to forecast waitlist trajectories of patients with MASH cirrhosis using data available at the time of waitlisting. Methods: A deep learning competing risk model was constructed using data from 17,551 waitlisted patients with MASH cirrhosis in the Scientific Registry of Transplant Recipients (SRTR) based on the DeepHit model framework with five-fold cross-validation. Model performance was evaluated and compared to single-risk Cox proportional hazards and random survival forests (RSF) models in predicting death or transplant using the concordance index and Brier score. Additionally, a novel performance metric, the competing event coherence (CEC) score, was developed to evaluate model performance in the setting of competing risks. Features associated with death and transplant in the DeepHit model were identified using permutation importance. Models were externally validated on data from the University Health Network. Results: A total of 17,551 patients were included. The mean MELD at listing was 19.4 (SD 8.1). At 120 months of follow-up on the waitlist, 54.6% (9599/17551) of patients underwent LT, 25.6% (4510/17551) of patients died or were removed due to deterioration, and 19.8% (3442/17551) of patients were removed for improvement or were censored. In a competing risk scenario, DeepHit achieved the best CEC scores at 1 (0.813), 3 (0.811), 6 (0.794), and 12 months (0.772) on the waitlist. The cause-specific RSF model had the highest concordance indices for death or transplant at all time points (death: 0.874 at 1 month, 0.840 at 6 months, and 0.814 at 12 months) except for death at 3 months, where DeepHit (0.883) outperformed RSF. RSF also had lower Brier scores overall, except for transplant at 12 months, where DeepHit outperformed RSF (0.206 vs 0.228). These results were similar on external validation. On feature importance assessment, MELD at listing and its components, as well as functional status, age, and blood type, were associated with death and transplant on the waitlist. Conclusions: A deep learning competing risk analysis can forecast the risks of both death and transplant in patients with MASH on the waitlist, helping to inform clinical decisions by identifying the most impactful covariates for each outcome.

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