What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Metabolic dysfunction-associated fatty liver disease (MASLD) (n=36839). Intervention: FIB-4 Index vs. Individuals without diabetes. Primary outcome: Optimal FIB-4 threshold for predicting MASLD (PDFF >5%).

What does this research mean for the field?

The optimal FIB-4 threshold for MASLD screening is significantly lower in individuals with diabetes (0.90-0.95) compared to the currently recommended threshold of 1.3 for the general population. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

What question did this study set out to answer?

The aim is to determine optimal FIB-4 thresholds for predicting metabolic dysfunction-associated fatty liver disease (MASLD) in individuals with and without diabetes.

June 7, 2026

2472-P: Differential FIB-4 Cutoffs for MASLD Screening by Diabetes Status

Key Result

The optimal FIB-4 threshold for MASLD screening is lower in individuals with diabetes (0.95) compared to those without diabetes (1.20).

Key Points

The aim is to determine optimal FIB-4 thresholds for predicting metabolic dysfunction-associated fatty liver disease (MASLD) in individuals with and without diabetes.
Included data from 1,273 diabetes and 35,566 non-diabetes participants from the UK Biobank.
Calculated FIB-4 using age, AST, ALT, and platelets; PDFF >5% used to identify MASLD.
Sensitivity, specificity, PPV, and Youden Index computed at 0.5-unit increments of FIB-4.
Optimal FIB-4 threshold for diabetes was 0.95 with sensitivity 71.6% and specificity 24.5%.
Optimal FIB-4 threshold for non-diabetes was 1.20 with sensitivity 46.2% and specificity 47.2%.
Similar findings in NHANES: threshold of 0.90 for diabetes and 1.00 for non-diabetes.

Study Design

Type

Cross-Sectional (n=36,839)

Multicenter

Yes

Structured PICO

What is the optimal FIB-4 threshold for MASLD screening in individuals with and without diabetes?

Population

36,839 fibrosis-free participants from the UK Biobank with laboratory and liver MRI data, with replication in NHANES, to evaluate FIB-4 thresholds for MASLD.

Exposure

FIB-4 Index for MASLD screening

Comparator

Currently recommended threshold of 1.3 for the general population

Outcome

Optimal FIB-4 threshold to maximize predictability of MASLD (identified by proton density fat fraction >5%)surrogate

The optimal FIB-4 threshold for MASLD screening is lower in individuals with diabetes compared to those without diabetes, suggesting the standard 1.3 cutoff may not be appropriate for diabetic patients.

Abstract

Introduction and Objective: The Fibrosis-4 Index (FIB-4) is a screening tool for metabolic dysfunction-associated fatty liver disease (MASLD), and a threshold of 1.3 is commonly used to determine high risk in the general population. However, whether this threshold is suitable for people with diabetes remains controversial. We aimed to determine the optimal FIB-4 thresholds to maximize predictability of MASLD in individuals with and without diabetes. Methods: Data from fibrosis-free participants with laboratory data and liver MRI measurements from the UK Biobank study were included (N = 1,273 for diabetes; N = 35,566 for non-diabetes). FIB-4 was calculated as age (years) × AST (U/L)/(platelets (109/L) × ALT (U/L)1/2. A proton density fat fraction (PDFF) 5% was used to identify MASLD. Sensitivity, specificity, positive predictive value (PPV), and Youden Index (sensitivity + specificity − 1) were computed at 0.5-unit increments of FIB-4 (range: 0.8 to 1.5). Analyses were replicated in NHANES using liver laboratory and imaging data from 2017 to 2020. Results: The optimal FIB-4 threshold for predicting MASLD was 0.95 for individuals with diabetes (Youden Index 4%, sensitivity 71.6%, specificity 24.5%, PPV 51.4%) and 1.20 for individuals without diabetes (Youden Index 6.6%, sensitivity 46.2%, specificity 47.2%, PPV 19.1%). Similar results were obtained in NHANES (i.e., threshold of 0.90 for diabetes: Youden Index 8.1%, sensitivity 63.9%, specificity 27.9%, PPV 74.5%; versus threshold of 1.00 for non-diabetes: Youden Index 2.84%, sensitivity 37.9%, specificity 67.8%, PPV 39%). Conclusion: Two large population-based studies showed that the optimal FIB-4 threshold for MASLD screening is lower in individuals with diabetes than the currently recommended threshold for the general population. Disclosure Y. Zu: None. Y. Yoshida: None. Funding American Diabetes Association (7-23-JDFWH-10), National Institute of General Medical Sciences of the National Institutes of Health (1P20GM152305), Administrative Supplement of the Louisiana Clinical & Translational Science Center (U54 GM104940), The Tulane Center of Excellence in Sex-Based Biology & Medicine (TCESBM)

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