Related Experiment Video
Updated: Feb 8, 2026
FIBS-enabled Noninvasive Metabolic Profiling
Published on: February 3, 2014
Metabolic biomarkers add little to diagnostic performance of FIB-4 in MASLD
Sofia Ullman1, Hannes Hegmar1,2, Johan Vessby3
1Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
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.
Insights
The Fibrosis-4 index (FIB-4) alone is effective for detecting advanced liver fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD) patients. Adding metabolic biomarkers like CRP or HbA1c did not significantly improve its diagnostic accuracy.
Area of Science:
- Hepatology
- Metabolic Diseases
- Diagnostic Biomarkers
Background:
- Advanced fibrosis is a key risk factor for liver complications in MASLD.
- The Fibrosis-4 index (FIB-4) is the primary screening tool for advanced fibrosis but has limitations.
- Metabolic biomarkers such as C-reactive protein (CRP), Hemoglobin A1c (HbA1c), HOMA-IR, and uric acid are commonly analyzed in MASLD patients.
Purpose of the Study:
- To evaluate if incorporating common metabolic biomarkers can enhance the diagnostic performance of FIB-4 for advanced fibrosis in MASLD.
- To compare the diagnostic accuracy of FIB-4 alone versus FIB-4 combined with CRP, HbA1c, HOMA-IR, or uric acid.
Main Methods:
- A cross-sectional study involving 276 adult MASLD patients from seven Swedish university hospitals.
- Advanced fibrosis was defined by liver stiffness measurement (LSM) ≥12 kPa.
- The diagnostic performance of FIB-4 and combinations with metabolic biomarkers was assessed using logistic regression and AUC analysis.
Main Results:
- Advanced fibrosis (LSM ≥12 kPa) was present in 16% of the patients.
- Combining FIB-4 with CRP, HbA1c, HOMA-IR, and uric acid yielded the highest AUC (0.810).
- This combined approach showed no statistically significant improvement over FIB-4 alone (AUC = 0.774).
Conclusions:
- Adding CRP, HbA1c, HOMA-IR, or uric acid to FIB-4 did not significantly improve the detection of advanced fibrosis in MASLD patients.
- These metabolic biomarkers appear to have limited additional value when used in conjunction with FIB-4 for this purpose.
- FIB-4 alone remains a valuable tool for initial assessment of advanced fibrosis in MASLD.
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