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

Abstract

BACKGROUND & AIMS: Fibrosis-4 (FIB-4) is the cornerstone of identifying clinically relevant liver disease among low-prevalence populations. However, its diagnostic accuracy is debated. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

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