Age-dependent differences in FIB-4 predictions of fibrosis in patients with MASLD referred from primary care

BACKGROUND: Fibrosis 4 (FIB-4) is widely used to triage patients with metabolic dysfunction-associated steatotic liver disease. Given that age is part of FIB-4, higher scores may be expected in the elderly population. This led to the proposal of using a higher threshold of FIB-4 to triage patients aged ≥65. Our main objective is to evaluate how age modifies the association between the FIB-4 index and disease severity based on the vibration-controlled transient elastography (VCTE) "rule of 5s." METHODS: In this cross-sectional study, we prospectively analyzed data from a primary care referral pathway. We used liver stiffness measurement by VCTE as a reference standard for liver risk. We modeled with ordinal regression the exceedance probabilities of finding different liver stiffness measurement thresholds according to FIB-4, and how age modifies FIB-4 predictions. RESULTS: Nine hundred eighty-five participants with complete data were used for modeling. Participants aged ≥65 had a higher prevalence of advanced liver disease estimated by VCTE and higher FIB-4 values than those <65 (85.9% vs. 20.2% for FIB-4 ≥1.3, and 46.5% vs. 6.5% for FIB-4 ≥2.0). In participants age ≥65, the negative predictive value for VCTE ≥10 kPa of FIB-4 <1.3 was 100% versus FIB-4 <2.0 was 83%. Age significantly modified FIB-4-based prediction of fibrosis, but predictions at a threshold of 1.3 or 2 were only minimally altered. For higher FIB-4 threshold (ie, 2.7), age strongly modified FIB-4 predictions of liver stiffness measurement. CONCLUSIONS: Age does not relevantly modify FIB-4 predictions when using the common threshold of 1.3. Our data suggest no rationale for increasing the FIB-4 threshold to 2 for undergoing further testing in patients aged ≥65. However, the meaning of a FIB-4 of 2.7 strongly changes with age. This cutoff for ages over 65 is not enough to define high-risk and would not warrant direct referral.