Formula
FIB-4 = (Age × AST) ÷ (Platelet count × √ALT)
Age in years · AST & ALT in U/L · Platelets in 10⁹/L
Interpretation
The AASLD/EASL 2023 NAFLD guidelines recommend a two-threshold approach to route patients to appropriate care:
| FIB-4 Score | Risk Category | Fibrosis Stage | Recommended Action |
|---|
| < 1.30 | Low risk | F0–F1 (none/mild) | Reassure; lifestyle modification; reassess 1–2 years |
| 1.30–2.67 | Indeterminate | F1–F3 | Second-line non-invasive test (LSM/ELF/Fibroscan) |
| > 2.67 | High risk | F3–F4 (advanced/cirrhosis) | Refer to hepatology; consider biopsy; HCC surveillance if cirrhosis |
Age-specific thresholds exist for patients over 65 years: <2.0 = low risk; >2.0 = high risk (reduces false positives in the elderly).
Clinical Application
- Population screening: FIB-4 is the recommended first-line fibrosis assessment tool in all patients with metabolic risk factors (obesity, T2DM, metabolic syndrome) or suspected NAFLD/NASH.
- Indeterminate zone (1.30–2.67): Proceed to liver stiffness measurement (FibroScan / VCTE) as a second-line test. ELF score, Pro-C3, or Enhanced Liver Fibrosis panel are alternatives. LSM ≥12 kPa suggests advanced fibrosis or cirrhosis; LSM ≥25 kPa is diagnostic of cirrhosis.
- High risk (>2.67) or cirrhosis confirmed: Begin 6-monthly abdominal ultrasound ± AFP for hepatocellular carcinoma surveillance. Assess for varices.
- HCV-treated patients: FIB-4 performed 24 weeks after SVR is reliable for post-treatment fibrosis staging.
- Limitations: FIB-4 can be falsely elevated by conditions that raise AST independently (haemolysis, hypothyroidism, strenuous exercise, muscle disease, statins) and in very young patients (<35 yrs). Thrombocytopenia from any cause raises FIB-4.
References
- Sterling RK, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV co-infection. Hepatology. 2006;43(6):1317–1325.
- Shah AG, et al. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2009;7(10):1104–1112.
- AASLD Practice Guidance. NAFLD/NASH — Diagnosis and Management. Hepatology. 2023.
- EASL Clinical Practice Guidelines. Non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol. 2021;75(3):659–689.