What are FIB-4 (Fibrosis-4) and APRI (Aspartate Aminotransferase-to-Platelet Ratio Index)?

What are FIB-4 and APRI?

FIB-4 (Fibrosis-4 Index) and APRI (Aspartate Aminotransferase-to-Platelet Ratio Index) are simple, blood-based, noninvasive scoring systems that use routine laboratory values to assess the severity of liver fibrosis in patients with chronic liver disease. 1, 2

FIB-4 Index

FIB-4 is the most validated and recommended first-line noninvasive test for identifying patients at low or high probability of advanced liver fibrosis. 2, 3

Calculation and Components

• FIB-4 uses four readily available laboratory values: age, AST (aspartate aminotransferase), ALT (alanine aminotransferase), and platelet count 2, 3
• The test is simple, inexpensive, and accessible in any clinical setting without requiring specialized equipment 3

Interpretation and Cutoff Values

• For NAFLD/MASLD: FIB-4 <1.3 reliably excludes advanced fibrosis in patients under 65 years; use <2.0 for patients ≥65 years to avoid false positives 2, 3
• Indeterminate zone: FIB-4 values between 1.3-2.67 require secondary testing with elastography or enhanced liver fibrosis testing 3
• High risk: FIB-4 >2.67 indicates high risk for advanced fibrosis and warrants hepatology referral 3
• For chronic hepatitis C: FIB-4 <1.45 excludes advanced fibrosis, while >3.25 suggests advanced fibrosis 2

Diagnostic Performance

• FIB-4 excels at ruling out advanced fibrosis with negative predictive values exceeding 90% at appropriate cutoffs 2, 3
• In chronic hepatitis C, FIB-4 demonstrated an AUC of 0.84 for diagnosing cirrhosis 1
• FIB-4 outperforms APRI for detecting both significant fibrosis (F2-F4) and advanced fibrosis (F3-F4) 3

APRI Score

APRI is another simple noninvasive marker that uses AST and platelet count to assess liver fibrosis, though it generally performs less well than FIB-4. 1

Calculation and Components

• APRI uses only AST level and platelet count in its calculation 1
• The formula is simpler than FIB-4 but may be less accurate in certain populations 1

Interpretation and Cutoff Values

• For significant fibrosis: Low cutoff values of 0.4-0.78 show sensitivity of 82% and specificity of 57% 1
• High cutoff for significant fibrosis: APRI ≥1.5 demonstrates sensitivity of 39% and specificity of 92% 1
• For cirrhosis: Low cutoff values of 0.75-1.0 show sensitivity of 77% and specificity of 78% 1
• High cutoff for cirrhosis: APRI ≥2.0 demonstrates sensitivity of 48% and specificity of 94% 1

Diagnostic Performance

• In chronic hepatitis C, APRI showed an AUC of 0.77 for diagnosing significant fibrosis and 0.83 for diagnosing cirrhosis 1
• APRI has suboptimal diagnostic performance in primary biliary cholangitis, with AUCs of 0.64-0.69 for various fibrosis stages 1

Comparative Performance

FIB-4 demonstrates superior diagnostic performance compared to APRI, particularly for diagnosing cirrhosis. 1, 4

• In chronic hepatitis B, FIB-4 showed higher AUROCs than APRI for both significant fibrosis (0.769 vs 0.704) and cirrhosis (0.869 vs 0.706) 4
• For chronic hepatitis C, FIB-4 exhibited superior diagnostic performance for cirrhosis compared to APRI, though performance for significant fibrosis was similar 1
• Both tests showed good performance in detecting patients without liver fibrosis when compared against FibroScan 5, 6

Important Limitations and Caveats

Both scores have significant limitations that must be considered when interpreting results. 1, 2

• Age effects: FIB-4 performs poorly in patients younger than 35 years and requires adjusted cutoffs (≥2.0) in those ≥65 years 2, 3
• Inflammation: APRI relies on AST alone, and FIB-4 incorporates AST and ALT, which may lead to overestimation in patients with acute intrahepatic inflammation 1
• Disease-specific accuracy: FIB-4 has lower accuracy in alcoholic liver disease and autoimmune hepatitis compared to viral hepatitis and NAFLD 3
• Positive predictive value: While both tests excel at excluding advanced fibrosis, they have only moderate positive predictive value for confirming advanced disease 2, 3

Clinical Application

Calculate FIB-4 in all patients with NAFLD, metabolic syndrome, type 2 diabetes, chronic viral hepatitis, or unexplained elevated liver enzymes. 2, 3

• Low-risk patients (FIB-4 <1.3 for age <65, or <2.0 for age ≥65) can be reassessed in 2-3 years 2
• Indeterminate-risk patients (FIB-4 1.3-2.67) require secondary testing with elastography or enhanced liver fibrosis testing 3
• High-risk patients (FIB-4 >2.67) should be referred to hepatology for comprehensive evaluation 3
• A two-tier approach (FIB-4 followed by elastography for indeterminate/high scores) maximizes diagnostic accuracy while minimizing unnecessary testing 2