Machine learning for predicting all-cause mortality of metabolic dysfunction-associated fatty liver disease: a longitudinal study based on NHANES

Abstract

Background: The mortality burden of metabolic dysfunction-associated fatty liver disease (MAFLD) is rising, making it crucial to predict mortality and identify the factors influencing it. While advanced machine learning algorithms are gaining recognition as effective tools for clinical prediction, their ability to predict all-cause mortality of MAFLD individuals remains uncertain. This study aimed to develop different machine learning models to predict all-cause mortality of MAFLD individuals, compare the predictive performance of these models, and identify the risk factors contributing all-cause mortality, which is crucial for management of MAFLD individuals.

Methods: We included 3921 MAFLD individuals in NHANES III. After a median follow-up time of 310 months, 1815 (46.3%) deaths were recorded. The data (demographic, behavioral factors and laboratory indicators) were utilized to construct machine learning models (Coxnet, RSF, GBS) after feature selection. Time-dependent AUC, time-dependent brier and C-index were then evaluated the performance of models. We identified the top five factors that contributed significantly to all-cause mortality and further explore the association with all-cause mortality using RCS and Kaplan-Meier survival curves.

Results: Coxnet showed the best performance in short-term and long-term predictions with time-dependent AUC of 0.82 at 5 years and 0.88 at 25 years. Age, FORNS, waist circumstance, AAR, FLI were associated positively with all-cause mortality. Compared to the individuals who smoked more than 100 cigarettes, those below 100 had better survival outcome (P < 0.0001).

Conclusions: Machine learning has a promising application in predicting all-cause mortality in MAFLD individuals. Combined the results of interpretable machine learning and association analyses, we found risk factors which contributing to the all-cause mortality. These findings provide insights for community health practitioners to intervene in modifiable risk factors, thereby improving the survival and quality of life of MAFLD individuals.

Keywords: All-cause mortality; Fatty liver; Machine learning; Metabolic dysfunction-associated fatty liver disease.

Fig. 1

The flowchart of this study

Fig. 2

Performance of different models predicting all-cause mortality of MAFLD. a Time-dependent AUC (b) C-index (c) Time-dependent brier. Abbreviations: COXNET, net-regularized cox proportional hazards model; GBS, gradient boosted

Fig. 3

Time-dependent AUROC of different models for predicting all-cause mortality (a)Coxnet, b Random Survival Forest, c Gradient Boosted Survival

Fig. 4

Summary plot of optimal model by SHAP

Fig. 5

Restricted cubic spline for the top four continuous variables of optimal model for predicting all-cause mortality

Fig. 6

Kaplan–Meier curves of categorical variable of number of cigarettes smoked