Background: Advanced fibrosis is the main risk factor for liver-related complications in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). The first line-test for evaluating presence of advanced fibrosis, Fibrosis-4 index (FIB-4), has limitations. Here, we investigated whether the diagnostic performance of FIB-4 could be improved by incorporating commonly analyzed metabolic biomarkers, including C-reactive protein (CRP), Hemoglobin A1c (HbA1c), the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), or uric acid.

Methods: This cross-sectional study included 276 adult (≥18 years) patients with MASLD from seven Swedish university hospitals. All patients underwent liver stiffness measurement (LSM) for assessment of advanced fibrosis, defined as LSM ≥12 kPa. The performance of FIB-4, CRP, HbA1c, HOMA-IR, and uric acid, alone and in combination, was assessed using logistic regression models. The area under the curve (AUC) was calculated.

Results: An LSM value of ≥12 kPa was found in 45 patients (16%). Combining FIB-4 with CRP, HbA1c, HOMA-IR, and uric acid yielded the highest AUC (0.810; 95% confidence interval [CI] = 0.732-0.889), which was not significantly better than the AUC for FIB-4 alone (0.774, 95%CI = 0.701-0.847).

Conclusions: Adding CRP, HbA1c, HOMA-IR, or uric acid to FIB-4 did not result in any statistically significant improvement in diagnostic performance, suggesting limited additional value of these biomarkers in identifying advanced fibrosis.