Machine-Learning-Enhanced Non-Invasive Testing for MASLD Fibrosis: Shallow-Deep Neural Networks Versus FIB-4, Tabular Foundation Models, and Large Language Models

Despite years of methodological progress, how far AI has come in liver fibrosis staging has never been systematically evaluated under the heterogeneous, multi-center conditions that define clinical practice. To address this gap, we introduce LiFS, a large-scale dataset and benchmark derived from the MICCAI 2025 CARE-Liver challenge, comprising 610 patients across multiple centers and scanners with multi-sequence MRI. To the best of our knowledge, LiFS is the first benchmark providing complete gadoxetic acid-enhanced sequences with histopathology-confirmed annotations from diverse real-world scanners. Through systematic evaluation of 9 independently developed methods selected from 96 registered teams against in-cohort radiologist reference results, our findings address how far current AI has progressed toward clinical-level liver fibrosis staging from three complementary perspectives. First, against radiologists, the best AI methods were broadly comparable to the senior radiologist and significantly exceeded the junior radiologist in selected settings, while median AI performance generally approached junior-radiologist levels. Second, from a data perspective, cross-center heterogeneity, label imbalance, and contrast-enhanced sequence variability emerge as the dominant challenges for AI methods. Third, from a technical perspective, methodological design choices, including spatial registration, input dimensionality, multi-modal fusion strategy, and backbone architecture, appear to modulate cross-center robustness, although no single choice alone closes the gap. Overall, LiFS provides a rigorous real-world benchmark for positioning the current state of AI in liver fibrosis staging and for enabling future research on the key challenges that limit clinically reliable deployment.

Non-alcoholic fatty liver disease (NAFLD) affects roughly 25% of global adults, posing substantial hepatic and cardiovascular risks. Yet, population-level screening tools remain inadequate. We present Method, a machine-learning framework for NAFLD risk prediction coupling gradient-boosted decision trees with conformal prediction to yield calibrated, distribution-free coverage guarantees on individual risk estimates. It integrates a mutual-information-based stability selection procedure to identify a compact, clinically interpretable feature subset via bootstrap resampling, constructing prediction sets whose marginal coverage provably exceeds a user-specified confidence level. We evaluated Method on a multicenter cohort from Guangzhou, China (primary n=2,187; external validation n=412) using 78 candidate features across demographics, metabolic biomarkers, and lifestyle factors. Method achieves an AUROC of 0.912 internally and 0.891 externally, outperforming deep neural networks, TabNet, support vector machines, and logistic regression. Conformal prediction sets achieve 91.3% empirical coverage at the 90% nominal level. A three-tier risk stratification derived from these scores separates the population into distinct groups, with the high-risk subgroup showing a 12-month progression rate 4.7 times that of the low-risk tier. The selected features -- notably waist circumference, ALT, GGT, triglycerides, fasting glucose, and BMI -- align with established metabolic risk factors, providing biological plausibility.

Adapting natural-image foundation models like DINOv3 to multi-modal medical imaging is challenging due to the significant domain gap between natural color images and multi-channel medical scans. We present a unified, patch-based framework that processes raw multimodal imaging through training-free registration, automated localization, and mask-filtered patch extraction. This architecture culminates in a hierarchical strategy that aggregates patch-level insights into subject-level diagnostics. Using liver fibrosis staging as a case study, we evaluate four patch-level feature representations: handcrafted Radiomics features, learned ResNet features, pre-trained foundation model SAM-Med2D features, and frozen DINOv3 features. To ensure a controlled comparison, all models utilize the same lightweight MLP head and are evaluated across both rigid and deformable registration settings. Our training protocol focuses on mild fibrosis (S1) and cirrhosis (S4) classes only, enabling a single classifier to address both substantial fibrosis detection and cirrhosis staging. Evaluated via 10 random train (90%)/ test (10%) splits on 360 subjects from the CARE 2025 Liver Track 4 cohort, our DINOv3-based framework significantly outperforms all baselines, achieving the best classification accuracy of 78.4% for S1 and 75.8% for S4.