The Fibrosis-4 (FIB-4) Index is a non-invasive scoring system developed to estimate the degree of liver fibrosis in patients with chronic liver disease, particularly those with hepatitis C and nonalcoholic fatty liver disease (NAFLD). It combines simple, routinely available clinical and laboratory parameters—age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count—to provide an estimate of fibrosis severity without the need for liver biopsy.
Since liver biopsy carries risks such as bleeding and sampling error, non-invasive markers like FIB-4 have become essential tools for risk stratification, treatment planning, and long-term monitoring of chronic liver disease.
Calculation Formula
The FIB-4 Index is calculated using the following formula:
FIB-4 = (Age × AST) / (Platelet count × √ALT)
- Age is in years
- AST and ALT are measured in U/L
- Platelet count is measured in 109/L
Interpretation of Scores
The FIB-4 Index provides cut-off values to rule out or suggest significant fibrosis:
- < 1.3: Low probability of advanced fibrosis (safe to monitor without biopsy in most cases)
- 1.3 – 2.67: Indeterminate; further testing with imaging or other non-invasive scores recommended
- > 2.67: High probability of advanced fibrosis or cirrhosis; further evaluation and management required
In patients over 65 years, a higher cut-off of 2.0 may be used for better specificity.
Clinical Significance
The FIB-4 Index is widely used in hepatology because of its simplicity and accuracy:
- Risk stratification: Helps identify patients at risk for advanced fibrosis or cirrhosis.
- Monitoring chronic liver disease: Useful in hepatitis B, hepatitis C, alcoholic liver disease, and NAFLD/NASH.
- Reducing need for biopsy: Non-invasive assessment reduces reliance on invasive procedures.
- Guiding therapy: Identifies patients who may benefit from antiviral therapy or closer follow-up.
- Public health and research: Provides an inexpensive, scalable tool for large population screening studies.
Indications for Use
The FIB-4 Index should be applied in:
- Patients with chronic viral hepatitis (HBV, HCV).
- Individuals with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH).
- Patients with alcoholic liver disease.
- Routine monitoring of liver fibrosis progression or regression after treatment.
Limitations
Despite its value, FIB-4 has important limitations:
- Indeterminate zone: Scores between 1.3 and 2.67 require additional testing such as elastography (FibroScan) or other biomarker panels.
- Age influence: Older patients may have falsely elevated scores due to age alone.
- Not specific to etiology: FIB-4 does not differentiate between causes of fibrosis.
- Laboratory variability: Differences in AST, ALT, and platelet measurements across labs can affect accuracy.
- Acute illness interference: Elevated transaminases due to acute hepatitis or other conditions may distort results.