How to investigate for Non-Alcoholic Fatty Liver Disease (NAFLD)?

Investigation Protocol for Non-Alcoholic Fatty Liver Disease (NAFLD)

Abdominal ultrasonography is the primary screening test for NAFLD, followed by non-invasive fibrosis assessment using clinical decision aids like NAFLD Fibrosis Score (NFS) or FIB-4 index to identify patients at risk for advanced fibrosis. 1

Initial Evaluation

• Assess for risk factors and comorbidities: obesity, diabetes mellitus, dyslipidemia, metabolic syndrome, hypertension, polycystic ovary syndrome, hypothyroidism, and sleep apnea 1
• Obtain detailed alcohol consumption history (significant consumption defined as >21 drinks/week for men and >14 drinks/week for women) 1
• Evaluate for persistent elevation of liver enzymes, though normal liver enzymes do not exclude NAFLD 1

Laboratory Testing

• Complete liver chemistry panel: ALT, AST, alkaline phosphatase, bilirubin, albumin, and prothrombin time 1
• Complete blood count with platelet count (for fibrosis assessment) 1
• Fasting blood glucose, HbA1c, and lipid profile 1
• Exclude other causes of liver disease:
  • Viral hepatitis serology (HBV, HCV) 1
  • Autoimmune markers (if clinically indicated) - note that low titers of autoantibodies are common in NAFLD and generally not clinically significant 1
  • Iron studies (ferritin, transferrin saturation) - consider genetic testing for hemochromatosis if persistently elevated 1

Imaging Studies

• Abdominal ultrasonography as first-line imaging modality 1
• Consider advanced imaging in selected cases:
  • Transient elastography (FibroScan) to assess liver stiffness/fibrosis 1
  • MRI or MR elastography for more accurate quantification of steatosis and fibrosis in cases where ultrasonography is inadequate 1

Non-invasive Fibrosis Assessment

• Calculate NAFLD Fibrosis Score (NFS) using age, BMI, presence of diabetes/impaired fasting glucose, AST/ALT ratio, platelet count, and albumin 1
  • NFS <-1.455: low risk for advanced fibrosis (90% sensitivity, 60% specificity) 1
  • NFS >0.676: high risk for advanced fibrosis (67% sensitivity, 97% specificity) 1
• Calculate FIB-4 index using age, AST, ALT, and platelet count 1
  • FIB-4 <1.45: low risk for advanced fibrosis 1
  • FIB-4 >3.25: high risk for advanced fibrosis 1

Liver Biopsy Considerations

• Liver biopsy remains the gold standard for diagnosis but is not required in all cases 1, 2
• Consider liver biopsy in the following scenarios:
  • Uncertain diagnosis after non-invasive assessment 1
  • Patients with high risk of advanced fibrosis based on non-invasive tests 1
  • Patients with persistently elevated liver enzymes and multiple risk factors 1
  • Patients with suspected NAFLD and persistently high serum ferritin with increased iron saturation, especially with C282Y HFE mutation 1

Common Pitfalls to Avoid

• Relying solely on liver enzymes for diagnosis - up to 50% of NAFLD patients have normal liver enzymes 1
• Failing to exclude significant alcohol consumption and other causes of hepatic steatosis 1
• Not assessing for advanced fibrosis, which is the strongest predictor of mortality in NAFLD 2
• Misinterpreting low-titer autoantibodies as indicative of autoimmune liver disease rather than as an epiphenomenon of NAFLD 1

Follow-up Recommendations

• Regular monitoring of liver enzymes every 3-6 months 3
• Periodic reassessment of fibrosis risk using non-invasive tests 1
• Management of associated metabolic conditions (diabetes, dyslipidemia, obesity) 1
• Consider referral to hepatology for patients with evidence of advanced fibrosis or cirrhosis 1