What does a Non-Alcoholic Fatty Liver Disease (NAFLD) fibrosis test screen for?

NAFLD Fibrosis Test: Screening for Advanced Fibrosis in Fatty Liver Disease

The NAFLD fibrosis test screens for the presence of clinically significant liver fibrosis (stage 2 or higher) in patients with non-alcoholic fatty liver disease, which is the most important predictor of liver-related morbidity and mortality. 1

Purpose and Components of NAFLD Fibrosis Tests

NAFLD fibrosis tests are non-invasive methods to identify patients who are at increased risk of having advanced liver fibrosis without requiring a liver biopsy. The most commonly used tests include:

FIB-4 Score

• Calculated using age, AST, ALT, and platelet count
• Most validated and recommended as first-line assessment 1
• Cut-off values:
  • <1.3: Low risk of advanced fibrosis (high negative predictive value of 92.7%)
  • 1.3-2.67: Intermediate risk

  • 2.67: High risk of advanced fibrosis 2

NAFLD Fibrosis Score (NFS)

• Calculated using six variables: age, BMI, hyperglycemia, platelet count, albumin, and AST/ALT ratio 3
• Cut-off values:
  • <-1.455: Advanced fibrosis can be excluded with high accuracy (negative predictive value of 88-93%)

  • 0.676: Presence of advanced fibrosis likely (positive predictive value of 82-90%) 1

Clinical Significance

Identifying advanced fibrosis is crucial because:

1. Mortality prediction: Fibrosis stage is the strongest predictor of liver and non-liver related outcomes in NAFLD patients 1

2. Treatment decisions: Patients with stage F2 or higher fibrosis may benefit from intensive lifestyle interventions or pharmacotherapy 1

3. Risk stratification: Allows clinicians to identify which patients need closer monitoring or referral to specialty care 1

4. Avoidance of unnecessary biopsies: Using these non-invasive tests can reduce the need for liver biopsies by approximately 75% 3

Two-Tier Testing Approach

Current guidelines recommend a two-tier approach for fibrosis assessment 1:

1. First tier: Simple non-proprietary scores (FIB-4 or NAFLD Fibrosis Score)
2. Second tier: For indeterminate results, proceed to:
   • Specialized blood tests (ELF test, FibroMeter)
   • Imaging-based elastography (vibration-controlled transient elastography, shear wave elastography, or MR elastography)

Limitations and Considerations

• FIB-4 and NFS have high negative predictive value but limited positive predictive value in low-prevalence settings 4
• Age affects the performance of these scores, with potentially different thresholds needed for older patients 1
• Obesity can limit the accuracy of some elastography techniques 1
• These tests identify fibrosis but cannot distinguish NASH from simple steatosis 1

Target Populations for NAFLD Fibrosis Testing

Testing is particularly recommended for three high-risk groups 1:

1. All patients with type 2 diabetes
2. Patients with two or more metabolic risk factors (obesity, hypertension, dyslipidemia, prediabetes)
3. Patients with incidental findings of hepatic steatosis or elevated aminotransferases

Clinical Algorithm for NAFLD Fibrosis Assessment

1. Calculate FIB-4 score for initial risk stratification
2. Based on results:
   • Low score (<1.3): Reassure and manage metabolic risk factors
   • Intermediate score (1.3-2.67): Proceed to second-tier testing
   • High score (>2.67): Consider referral for specialist evaluation

By implementing this approach, clinicians can identify patients at highest risk for adverse liver-related outcomes and prioritize appropriate interventions to reduce morbidity and mortality.