FIB-4-based Referral Pathways Have Suboptimal Accuracy to Identify Increased Liver Stiffness and Incident Advanced...

Fibrosis-4 (FIB-4) is the cornerstone of identifying clinically relevant liver disease among low-prevalence populations. However, its diagnostic accuracy is debated.

Participants with metabolic dysfunction from the National Health and Nutrition Examination Survey (NHANES) 2017 to 2020 and Apolipoprotein MOrtality RISk (AMORIS) were used for cross-sectional and longitudinal analysis, respectively. The ability of the FIB-4-based referral pathways to detect individuals with increased liver stiffness (LSM) and/or International Classification of Diseases-based incident advanced liver disease was investigated. Additional analysis included the application of an age-adjusted cutoff.

Cross-sectional analysis comprised 6375 participants (age, 52 years [interquartile range, 36-64 years]; 49% male), of whom 10.3% had LSM ≥8, 3.4% LSM ≥12 and 28% FIB-4 ≥1.3. Among those considered to have no clinically relevant liver disease (72%), LSM ≥8, 12, and 15 kPa was still present in 8.5%, 2.3%, and 1.1%, respectively. The FIB-4 had 0.0% sensitivity for increased LSM among participants aged 18 to 35 years and a high referral rate (71%) among participants aged 65 to 80 years or low sensitivity (34%) with the age-adjusted cutoff. However, in the longitudinal analysis (n = 53,766; age, 54 years [interquartile range, 45-61]; male 65%; events 132), FIB-4 detected 74% of 5-year incident cases of advanced liver disease (cirrhosis or hepatocellular carcinoma).

FIB-4-based referral pathways to identify liver disease among the general population result in a high referral rate while not detecting approximately 60% of LSM ≥8, 50% of LSM ≥12, 40% of LSM ≥15, and 25% of incident advanced liver disease. Current referral pathways to detect precirrhotic liver disease in low-prevalence populations could benefit from further optimization.