What labs are used to diagnose liver fibrosis?

Laboratory Tests for Liver Fibrosis Assessment

Use FIB-4 and APRI as first-line serum markers for liver fibrosis screening, followed by imaging-based tests like transient elastography when serum markers indicate intermediate or high risk. 1

Primary Serum Biomarkers

Laboratory assessment of liver fibrosis relies on two categories of serum markers that can be obtained through routine blood work 1:

Indirect Markers (Reflecting Liver Damage)

These are the most commonly used and include:

• AST (Aspartate aminotransferase) 1
• ALT (Alanine aminotransferase) 1
• Platelet count 1
• Total bilirubin 1
• Prothrombin time/INR 1
• Gamma-glutamyl transpeptidase (GGT) 1
• Albumin 1
• Haptoglobin 1
• α2-macroglobulin 1
• Apolipoprotein A1 1
• Cholesterol 1

Direct Markers (Measuring Fibrogenesis)

These measure components released during extracellular matrix remodeling:

• Hyaluronic acid (HA) 1
• TIMP-1 (Tissue inhibitor of metalloproteinase 1) 1
• PIIINP (Amino terminal peptide of procollagen III) 1

Validated Scoring Systems

Individual markers have poor diagnostic performance, so validated algorithms combining multiple parameters are essential 1:

Most Widely Recommended Scores

FIB-4 (Fibrosis-4 Index) - First-line test 1:

• Formula: Age (years) × AST (IU/L) / [Platelet count (10⁹/L) × √ALT (IU/L)]
• FIB-4 <1.3: Rules out advanced fibrosis (90% accuracy) 1
• FIB-4 >2.67: Indicates advanced fibrosis (80% accuracy) 1
• For patients ≥65 years: Use cutoff of <2.0 for low risk 1

APRI (AST-to-Platelet Ratio Index) - Alternative first-line test 1, 2:

• Formula: (AST [IU/L] / AST ULN [IU/L]) / Platelet count [10⁹/L] × 100
• Validated in chronic hepatitis C and NAFLD 1

Disease-Specific Scores

NAFLD Fibrosis Score (NFS) - For metabolic liver disease 1:

• Formula: -1.675 + 0.037 × age + 0.094 × BMI + 1.13 × diabetes (yes=1, no=0) + 0.99 × AST/ALT ratio - 0.013 × platelet count - 0.66 × albumin
• NFS <-1.455: Excludes advanced fibrosis 1
• NFS >0.676: Indicates advanced fibrosis 1

Enhanced Liver Fibrosis (ELF) Score - Proprietary panel 1:

• Combines hyaluronic acid, TIMP-1, and PIIINP 1
• ELF >9.8: High risk of liver-related mortality 3
• ELF cutoff 0.3576 for advanced fibrosis (AUC 0.90) 1

Additional Validated Scores

BARD Score - For NAFLD 1:

• AST/ALT ratio ≥0.8 = 2 points, BMI ≥28 kg/m² = 1 point, diabetes = 1 point

Forns Index - For chronic hepatitis C 1:

• Formula: 7.811 - 3.131 × ln(platelet count) + 0.781 × ln(GGT) + 3.467 × ln(age) - 0.014 × cholesterol

FibroTest® - Proprietary algorithm 1:

• Combines total bilirubin, GGT, α2-macroglobulin, apolipoprotein A1, and haptoglobin, adjusted for age and sex

Clinical Algorithm for Laboratory Assessment

Step 1: Initial Screening 1

• Order basic labs: AST, ALT, platelet count, albumin
• Calculate FIB-4 or APRI
• Add age, BMI, diabetes status for NFS if NAFLD suspected

Step 2: Risk Stratification 1

• Low risk (FIB-4 <1.3 or <2.0 if age ≥65): Reassess in 1-3 years
• Intermediate risk (FIB-4 1.3-2.67): Proceed to imaging (transient elastography) or refer to hepatologist
• High risk (FIB-4 >2.67): Immediate hepatology referral and imaging confirmation

Step 3: Advanced Testing for Intermediate Risk 1

• Consider ELF panel if available
• Order M2BPGi or AsAGP if accessible
• Proceed to vibration-controlled transient elastography (VCTE) or MRE

Important Clinical Caveats

Age-related considerations: FIB-4 and NFS incorporate age, which can lead to false positives in elderly patients (use adjusted cutoffs) 1, 4

Disease-specific limitations: FIB-4 diagnostic accuracy may be lower in NAFLD patients with type 2 diabetes 1

AST/ALT ratio alone has poor diagnostic performance despite historical use for cirrhosis detection 1

Discordant results between different scoring systems require imaging confirmation or liver biopsy 1

Serial monitoring: Repeat FIB-4 every 1-2 years in high-risk patients (prediabetes, type 2 diabetes, metabolic risk factors) and every 2-3 years in lower-risk NAFLD patients 1

Prognostic Value

Elevated scores predict mortality risk: An ELF score >9.8 indicates high risk of liver-related mortality, with mortality risk increasing 16.69-fold for F3 fibrosis and 42.30-fold for F4 (cirrhosis) 3

Younger age with advanced fibrosis carries worse prognosis due to more years of life lost 3