Comparison of diagnostic accuracy and utility of non-invasive tests for clinically significant liver disease in a general population with metabolic dysfunction

Kleef, L.A. van; Pustjens, J.; Schattenberg, J.M.; Holleboom, A.G.; Cabezas, M.C.; Tushuizen, M.E.; ... ; Brouwer, W.P. (2025)

Article / Letter to editor

Background: Screening for liver disease in the general population requires accurate non-invasive tests (NITs). A head-to-head comparison of NITs for early detection of clinically relevant liver disease among the target population for screening is lacking.

Methods: Among meta-cohort (Rotterdam Study and NHANES) with metabolic dysfunction aged 18-80 years, 10 NITs were investigated. The diagnostic accuracy for clinically relevant conditions (increased liver stiffness measurement [LSM], at-risk MASH, advanced fibrosis or cirrhosis) was assessed. Subgroup analysis included stratification by age group and diabetes/obesity status.

Results: We analysed 11,404 participants. MAF-5 obtained the highest AUC for increased LSM (>= 8kPa:0.80; >= 12kPa:0.87) and advanced fibrosis (AUC:0.90). FNI and MAF-5 performed best for detecting MASH (AUC:0.93 and AUC:0.92, P=ns) and SAFE for cirrhosis (AUC:0.92). To obtain 80% sensitivity for LSM >= 8kPa, the corresponding MAF-5 cut-off resulted in fewer referrals (42%) compared to FIB-4 (77%) and higher specificity (62% vs. 24%); MAF-5 was also superior for detection of LSM >= 12kPa and advanced fibrosis. Age-dependent scores yielded lower sensitivity amongst younger individuals e.g., by referring 20% of the population with highest NIT-scores, the FIB-4, SAFE, NFS, FORNS and HFS yielded <10% sensitivity for LSM >= 8kPa amongst individuals aged 18-35y while FNI and MAF-5 obtained 40% and 71%.

Conclusions: Of the 10 investigated NITs, MAF-5 discriminated best between all conditions except cirrhosis, for which SAFE yielded the highest accuracy. The performance of FIB-4 was poor, implying that referral pathways for significant liver disease in low-prevalence populations can be improved when more accurate NITs such as MAF-5 are employed.

• epidemiology
• External validation
• fibrosis risk prediction
• general population
• MASLD
• screening
• SLD

• All authors: Kleef, L.A. van; Pustjens, J.; Schattenberg, J.M.; Holleboom, A.G.; Cabezas, M.C.; Tushuizen, M.E.; Knegt, R.J. de; Ikram, M.A.; Janssen, H.L.A.; Francque, S.M.; Brouwer, W.P.
• Date: 2025-05-07
• Journal: Hepatology
• Volume: 83
• Issue: 3
• Pages: 591 - 602
• DOI: doi:10.1097/HEP.0000000000001356