Thursday, June 25, 2026

Clinical Tools · Hepatic Fibrosis · NASH / MASLD

FIB-4 Index Calculator

Calculate the FIB-4 liver fibrosis index from age, AST, ALT, and platelet count. Built for advanced fibrosis screening, NASH/MASLD trial context, and linkage to hepatic impairment assessment.

Quick Answer

The FIB-4 index estimates advanced liver fibrosis (Metavir F3–F4) from age, AST, ALT, and platelet count: FIB-4 = (Age × AST) / (Platelets × √ALT). Scores below 1.45 suggest low risk, 1.45–3.25 indeterminate, above 3.25 high risk. Pharma teams use FIB-4 for NASH/MASLD trial enrichment and hepatic impairment screening — a non-invasive alternative to biopsy when paired with elastography.

FIB-4 formula
FIB-4 = (Age [years] × AST [U/L]) / (Platelets [×10⁹/L] × √ALT [U/L])
Low risk < 1.45 · Indeterminate 1.45–3.25 · High risk > 3.25 (advanced fibrosis F3-F4).

Calculate FIB-4 Index

Enter age, AST, ALT, and platelet count from the same clinical assessment window when possible.

Laboratory values

Must be greater than zero; the formula uses √ALT.

Standard CBC units (e.g. 210 = 210 ×10⁹/L).

Advanced fibrosis risk

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FIB-4 score
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index
Age
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years
AST
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U/L
ALT
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U/L
Platelets
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×10⁹/L
√ALT
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U/L0.5

How to Use the FIB-4 Calculator

1
Collect age, AST, ALT, and platelet count from the same blood draw when possible to avoid temporal mismatch.
2
Confirm platelet units are ×10⁹/L (standard CBC reporting). Do not enter platelets in /μL without converting.
3
Calculate FIB-4 and review whether the score falls below 1.45, between 1.45 and 3.25, or above 3.25.
4
Use indeterminate or high scores to guide further workup (elastography, specialist referral, biopsy per protocol)—not as a standalone diagnosis.

Worked Example

Example calculation

Inputs: age 52 years, AST 45 U/L, ALT 38 U/L, platelets 210 ×10⁹/L.

Calculation: FIB-4 = (52 × 45) / (210 × √38) = 2340 / (210 × 6.16) = 2340 / 1294 ≈ 1.81.

Interpretation: 1.81 falls in the indeterminate range (1.45–3.25). Consider transient elastography or specialist assessment per local pathway.

FIB-4 Interpretation Bands

Low risk < 1.45

Low likelihood of advanced fibrosis (F3-F4). Useful for ruling out advanced fibrosis in appropriate populations.

Indeterminate 1.45 – 3.25

Intermediate probability. Further assessment with elastography, imaging, or biopsy may be warranted.

High risk > 3.25

Higher likelihood of advanced fibrosis (F3-F4). Prompts specialist referral and additional staging in most pathways.

NASH / MASLD Context for Pharma Professionals

FIB-4 is widely used in metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD/NASH) screening algorithms and clinical trial operations. Sponsors may use FIB-4 thresholds to enrich populations (e.g., F2-F3 fibrosis by biopsy with FIB-4 corroboration), exclude patients with likely cirrhosis, or track non-invasive fibrosis trends alongside histologic endpoints.

FIB-4 estimates fibrosis risk; it does not replace Child-Pugh classification for hepatic impairment pharmacokinetics. When advanced fibrosis progresses to decompensated cirrhosis, drug development teams map hepatic impairment using Child-Pugh A/B/C in PK studies and labeling. Use our Child-Pugh Score Calculator for cirrhosis severity and dosing-context interpretation.

In registrational NASH trials, primary endpoints remain histology-driven (fibrosis stage improvement, NASH resolution). FIB-4 may appear as a secondary or exploratory biomarker, but regulatory acceptance as a surrogate endpoint requires dedicated validation programs.

Limitations and Caveats

FIB-4 performance varies by etiology, age, and comorbidity. Age in the numerator raises scores in older adults; platelets in the denominator amplify the effect of thrombocytopenia from portal hypertension but also confound when platelets are low for non-hepatic reasons.

Do not use FIB-4 during acute hepatitis flares, when AST/ALT reflect muscle injury, or when platelet count is unreliable. The indeterminate zone (1.45–3.25) has meaningful false-positive and false-negative rates—confirmatory testing is often required.

FIB-4 screens for advanced fibrosis risk; it does not stage mild fibrosis precisely, assess portal hypertension, or determine Child-Pugh class. Always integrate clinical context, imaging, elastography, and protocol-specific requirements.

Interpretation Reference Table

FIB-4 score Risk category Advanced fibrosis (F3-F4) Typical next step
< 1.45 Low risk Unlikely Continue routine monitoring per guidelines; repeat if clinical context changes
1.45 – 3.25 Indeterminate Uncertain Consider FibroScan/elastography, specialist referral, or biopsy per pathway
> 3.25 High risk Likely Hepatology referral, elastography, cirrhosis workup, variceal/HCC surveillance if confirmed

Evidence & sources

Frequently Asked Questions

The FIB-4 index is a non-invasive serum marker used to estimate the likelihood of advanced liver fibrosis (Metavir F3-F4). It combines age, AST, ALT, and platelet count into a single score that can help screen patients with chronic liver disease without immediate liver biopsy.
FIB-4 = (Age [years] × AST [U/L]) / (Platelets [×10⁹/L] × √ALT [U/L]). Age is in years, AST and ALT are in U/L, and platelet count is in ×10⁹/L (the same units reported on a standard CBC differential).
Standard interpretation uses two cutoffs: below 1.45 suggests low risk of advanced fibrosis (F3-F4), 1.45 to 3.25 is indeterminate, and above 3.25 suggests high risk of advanced fibrosis. These thresholds are screening aids, not diagnostic proof of cirrhosis.
FibroScan (transient elastography) measures liver stiffness in kilopascals and can estimate fibrosis stage directly. FIB-4 uses routine blood tests and is cheaper and more widely available, but it is less precise in the indeterminate range. Many hepatology pathways use low FIB-4 to rule out advanced fibrosis and high FIB-4 or indeterminate scores to trigger elastography or biopsy.
APRI (AST to Platelet Ratio Index) uses only AST and platelets: (AST/ULN) / Platelets [×10⁹/L] × 100. FIB-4 adds age and ALT, which can improve performance in some populations but also introduces age-related bias. APRI is simpler; FIB-4 is often preferred in NAFLD/NASH screening algorithms because it incorporates ALT variability.
Phase 2 and 3 NASH/MASLD trials frequently use non-invasive fibrosis markers for patient selection, stratification, and secondary endpoints. FIB-4 may appear in inclusion criteria (e.g., excluding advanced fibrosis), as a baseline covariate, or as part of composite histologic/non-invasive response assessments alongside liver biopsy, MRI-PDFF, or elastography.
Avoid relying on FIB-4 alone in acute hepatitis, acute-on-chronic liver failure, hemolysis, recent transfusion, active alcohol binge, HIV with uncontrolled viremia, extrahepatic thrombocytopenia, splenomegaly from non-hepatic causes, or when AST/ALT are markedly elevated from muscle injury. It was validated primarily in chronic viral hepatitis and NAFLD cohorts.
Age is in the numerator of the FIB-4 formula, so older patients tend to score higher even with similar liver histology. This can increase false-positive rates for advanced fibrosis in patients over 65. Some guidelines apply age-adjusted cutoffs or lower specificity expectations in older adults.
Platelets are in the denominator, so thrombocytopenia from portal hypertension increases FIB-4, while thrombocytosis or reactive platelet elevation can lower it. Non-hepatic causes of low platelets—ITP, chemotherapy, infection, or bone marrow disorders—can distort the score and should prompt caution.
FIB-4 estimates advanced fibrosis risk before decompensation, while Child-Pugh classifies cirrhosis severity using bilirubin, albumin, INR, ascites, and encephalopathy. A patient may have elevated FIB-4 with compensated cirrhosis (Child-Pugh A) or indeterminate FIB-4 with later decompensation. For hepatic impairment drug dosing, Child-Pugh remains the regulatory standard—see our Child-Pugh calculator for dosing context.
No. FIB-4 estimates probability of advanced fibrosis; it does not confirm cirrhosis, stage individual fibrosis with biopsy-level precision, or assess portal hypertension complications. Definitive staging still requires liver biopsy, elastography with validated cutoffs, or integrated clinical-pathologic assessment.
Regulatory endpoints in NASH trials still rely heavily on histology (NAS, fibrosis stage). FIB-4 and other non-invasive tests may support enrichment, safety monitoring, or exploratory endpoints, but they generally cannot substitute for protocol-specified biopsy readouts in registrational studies without explicit FDA/EMA agreement.

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