Evaluating noninvasive tests for significant fibrosis in a population-based MASLD cohort: insights from NHANES 2017-2020
Recommended Citation
Dunn W, Cheuk-Fung Yip T, Adams L, Verma N, Wai-Sun Wong V, Castera L, Abdelmalek MF, Singal AK, Dunn N, Chen V, Lai-Hung Wong G, Jafri S, Arab JP, Dubourg J, Duseja AK, Ahmed W, Diaz LA, Zhong B, Alkhouri N. Evaluating noninvasive tests for significant fibrosis in a population-based MASLD cohort: insights from NHANES 2017-2020. J Hepatol 2025; 82:S577.
Document Type
Conference Proceeding
Publication Date
5-1-2025
Publication Title
J Hepatol
Abstract
Background and aims: Resmetirom is FDA-approved for metabolic dysfunction-associated steatotic liver disease (MASLD) with signifi cant (F2) to advanced (F3) fibrosis. While current AASLD guidance recommended Vibration-Controlled Transient Elastography for treat ment consideration, limited availability highlights the need for noninvasive tests (NITs) using common laboratory parameters. Most existing NITs were developed in tertiary referral centers and are not optimized for screening significant fibrosis in general populations. This study compares among ALADDIN-F2-Lab, FIB-4, NAFLD Fibrosis Score (NFS), SAFE, and Liver Risk Score for identifying significant fibrosis or higher in a population based cohort. Method: The National Health and Nutrition Examination Survey (NHANES) 2017–2020 database was used. NHANES survey design weights, strata, and clusters ensured nationally representative estimates. Adults (≥ 18 years) with steatotic liver disease (CAP ≥ 248 dB m) and at least one cardiometabolic risk factor were included. Alcohol intake was calculated from survey responses, and patients with alcohol intake ≥ 20 g day for females, ≥ 30 g day for males, viral hepatitis, or missing liver stiffness measurement (LSM) were excluded. Significant fibrosis was defined as LSM ≥ 8 kPa. NITs including ALADDIN-F2-Lab, FIB-4, NFS, SAFE Score, and Liver Risk Score were categorized into low, intermediate, and high-risk groups using published cutoffs. Results: Among 4,022 participants with MASLD, 16.0% (SE 1.4%) had significant fibrosis (≥ 8 kPa). ALADDIN-F2-Lab, FIB-4, and Liver Risk Score classified the majority of participants as low risk, at 80.4%, 74.7%, and 96.1%, respectively, making them suitable for community based screening. Among these, ALADDIN-F2-Lab demonstrated the highest sensitivity (36.5%), followed by FIB-4 (32.5%) and Liver Risk Score (10.2%). NFS displayed a comparable sensitivity (33.8%) but identified only 33.4% as low risk. SAFE Score achieved the highest sensitivity (85.5%) but classified only 30.8% of participants as low risk. For high-risk classification, ALADDIN-F2-Lab (83.7%), FIB-4 (76.1%), NFS (80.9%), and Liver Risk Score (94.2%) demonstrated excellent specificity. ALADDIN-F2-Lab achieved the highest PPV (69.6%) due to fewer patients being classified as high risk. Conclusion: While ALADDIN-F2-Lab demonstrated the highest PPV among NITs for high-risk classification and SAFE achieved superior sensitivity, no NIT showed sufficient sensitivity (<50%) to reliably identify the majority of patients with significant fibrosis (LSM ≥ 8 kPa) in a general population cohort. This highlights the challenge of applying NITs derived from tertiary centers to broader, community-based settings. Reassessing existing cutoffs and optimizing NITs for use in general populations may improve their utility as first-line screening tools for significant fibrosis or higher. Until such adjustments are made, their adoption in clinical practice should be approached with caution.
Volume
82
First Page
S577
