Patients with NASH, NAS≥4, and F≥2 (Fibro-NASH) are at highest risk for disease progression.
➢Patients with Fibro-NASH are targeted for proof-of-concept NASH trials.
➢MRI-PDFF and MR elastography are the most common primary and secondary endpoints in NASH trials, respectively.
➢To identify Fibro-NASH, the MRI-AST (MAST) score was created based on these MRI techniques.
➢The MAST score was proven to outperform the Fib-4, NAFLD fibrosis, and FAST scores.


Abstract
Background and Aims
A priority is identification of patients with fibrotic nonalcoholic steatohepatitis (Fibro-NASH) defined as NASH with nonalcoholic fatty liver disease activity score ≥ 4 and significant fibrosis (≥ F2). These patients are at highest risk for disease progression and will benefit most from pharmacologic treatment. MRI-based proton density fat fraction (MRI-PDFF) and MR elastography (MRE) risk-stratifies NAFLD patients by assessing steatosis and fibrosis, respectively. We developed a highly specific MRI-based score to identify Fibro-NASH patients.


Methods
This analysis included derivation (n=103) and validation (n=244) cohorts from tertiary care centers who underwent MRI, liver biopsy, Transient elastography, and laboratory testing for NAFLD from 2016-2020. To identify Fibro-NASH, a formula was developed based on MRI-PDFF, MRE, and a third variable with highest balanced accuracy per logistic regression. The MRI-AST (MAST) score was created and compared to NAFLD fibrosis (NFS), Fib-4, and FAST scores.


Results
The MAST score in the validation cohort demonstrated high performance and discrimination [ROC AUC 0.93 (0.88-0.97), 95% CI]. In the validation cohorts, the 90% specificity cutoff of 0.242 corresponded to sensitivity 75.0%, PPV 50.0% and NPV 96.5%, whereas the 90% sensitivity cutoff of 0.165 corresponded to specificity 72.2%, PPV 29.4%, and NPV 98.1%. Compared to NFS and Fib-4, MAST had fewer indeterminate score patients and overall higher AUC. Compared to FAST, MAST exhibited better ROC and overall better discrimination.


Conclusion
The MAST score is an accurate, MRI-serum-based score that outperforms previous scores in noninvasively identifying patients at higher risk of Fibro-NASH.


Lay Summary
A major priority is identification of patients with nonalcoholic steatohepatitis and significant fibrosis who need treatment and are at risk for clinical liver-related outcomes. We developed a more accurate score using MRI advanced technologies and a laboratory blood test (AST) that outperforms previous non-invasive scores in identifying patients at higher risk of liver disease progression.

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