Evaluating Liver Health: Understanding FIB-4 Calculation and Interpretation

Liver Disease Stages

Cleveland Clinic encourages proactive screening for MASH (metabolic dysfunction–associated steatohepatitis), a progressive form of fatty liver disease previously known as NASH.^[1]

MASH currently affects an estimated 5–7% of U.S. adults, and its prevalence is projected to increase to about 7.9% by 2050, driven largely by rising rates of obesity and type 2 diabetes, according to studies published in Diabetes Care and by the American Liver Foundation.^[2]

What is FIB-4 Screening?

MASH occurs when excess fat accumulates in liver cells, causing inflammation and cellular damage. Unlike many medical conditions that rely on a single screening test, MASH lacks a universal diagnostic tool.

“The most effective approach is a two‑step screening strategy,” notes Dr. Laique.

1. Calculate the Fibrosis‑4 (FIB‑4) index: This is performed using routine blood tests.
2. Follow-up with VCTE (FibroScan): If the FIB‑4 index is elevated, vibration‑controlled transient elastography is used to assess liver fat levels (categorized as mild, moderate, or severe) and liver stiffness, which indicates the degree of fibrosis (scarring).

Fibrosis-4 index

The Fibrosis‑4 (FIB‑4) index is a simple, non‑invasive score derived from routine blood tests to estimate the risk of advanced liver fibrosis (scarring) in people with chronic liver disease—particularly MASH. It helps identify patients who may require further evaluation, such as advanced imaging (e.g., FibroScan) or referral to a specialist, while also ruling out low‑risk cases without the need for invasive procedures like liver biopsy.

FIB‑4 is recommended as a first‑line screening tool by organizations such as the American Association for the Study of Liver Diseases (AASLD), especially for individuals at higher risk, including those with obesity, type 2 diabetes, or metabolic syndrome.

Role in MASH Screening

• Why use it? MASH can progress silently to cirrhosis. Early detection of fibrosis allows interventions (lifestyle changes, weight loss, or emerging drugs like resmetirom) to halt progression.
• Screening process: In high-risk patients (e.g., type 2 diabetes, obesity), calculate FIB-4 from routine labs. If ≥1.3 (as mentioned in contexts like Cleveland Clinic resources), proceed to non-invasive imaging like FibroScan to measure liver stiffness and confirm fibrosis.
• Advantages: High accuracy for excluding advanced disease; reduces unnecessary referrals/biopsies.
• Limitations: Less accurate for intermediate fibrosis; can miss some cases in obese/diabetic patients. Often paired with other tests (e.g., ELF or NAFLD Fibrosis Score) for better precision.

Consult a healthcare provider for personalized calculation and interpretation, as values depend on individual labs and risk factors. Regular re-testing can track changes over time.

How is FIB-4 Calculated?

The formula uses four routine lab values:

• Age: Patient's age in years
• AST: Aspartate aminotransferase level (elevated in liver damage)
• ALT: Alanine aminotransferase level (often higher in fatty liver)
• Platelets: Platelet count (low counts suggest advanced fibrosis due to portal hypertension)

Notes:

• IU/L (International Units per Liter) and U/L (Units per Liter) both mean units per liter, and in clinical lab tests—such as AST, ALT, and ALP—they’re used interchangeably. One IU equals one U for these enzyme assays.
• ×10³/µL and ×10⁹/L are equivalent units for platelet counts—the numerical values stay the same.  For example, a range of 150–450 ×10³/µL (150,000–450,000 platelets per microliter) is identical to 150–450 ×10⁹/L in SI units.

These values are commonly available from standard blood tests, making FIB-4 cost-effective and accessible in primary care.

Interpretation of FIB-4 Scores (for MASH/NAFLD/MASLD)

Cutoffs vary slightly by guideline and population, but common thresholds for ruling out or identifying advanced fibrosis (typically F3-F4 stages) are:^[3]

FIB-4 Score	Risk Level	Interpretation	Next Steps
<1.3	Low risk	High negative predictive value (~90-95%); advanced fibrosis very unlikely.	Routine monitoring; no immediate further testing needed.
1.3–2.67	Indeterminate/intermediate	Possible fibrosis; further assessment required.	Proceed to second-line tests (e.g., FibroScan/vibration-controlled transient elastography for liver stiffness measurement).
>2.67	High risk	Likely advanced fibrosis (positive predictive value ~80%).	Refer to specialist (hepatology/gastroenterology); consider additional imaging or biopsy if needed.

Important Notes:

• Some sources use a lower low-risk cutoff (<1.45) or higher high-risk (>3.25), originally from hepatitis C studies, but for MASH, 1.3 and 2.67 are more commonly applied due to better performance in fatty liver populations.
• Age adjustment: FIB-4 performs best in ages 35–65; it may overestimate risk in older patients (>65) or underestimate in younger ones.^[6]

Source: AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease^[8]

References

1. Understanding Your MASH Test Results
2. Estimated Burden of Metabolic Dysfunction–Associated Steatotic Liver Disease in US Adults, 2020 to 2050
3. Use of the FIB4 Index for Non-Invasive Evaluation of Fibrosis in Nonalcoholic Fatty Liver Disease 
4. Fibrosis-4 (FIB-4) Index for Liver Fibrosis (Online Calculator)
5. FIB-4 (Fibrosis-4) Calculator
6. Age as a Confounding Factor for the Accurate Non-Invasive Diagnosis of Advanced NAFLD Fibrosis
7. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease
8. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease