What is the workup for Non-Alcoholic Steatohepatitis (NASH) Liver Disease (NASHLD)?

Comprehensive Workup for Non-Alcoholic Steatohepatitis Liver Disease (NASHLD)

The workup for NASHLD should include a thorough initial assessment with specific laboratory tests, imaging, and risk stratification to determine the need for liver biopsy, which remains the gold standard for definitive diagnosis.

Initial Evaluation

Medical History and Risk Assessment

• Detailed alcohol consumption history (must be <21 drinks/week for men, <14 drinks/week for women) 1
• Assessment of metabolic risk factors (obesity, type 2 diabetes, dyslipidemia, hypertension) 1
• Medication review to exclude drugs associated with steatosis (tamoxifen, amiodarone, methotrexate, corticosteroids) 1
• Family history of diabetes, cardiovascular disease, and liver disease 1

Physical Examination

• BMI and waist circumference measurements 1
• Signs of metabolic syndrome
• Assessment for hepatomegaly and other signs of chronic liver disease

Laboratory Testing

First-Line Tests

• Liver enzymes: ALT, AST, GGT 1
• Complete metabolic panel including glucose, HbA1c 1
• Lipid profile (total cholesterol, HDL, LDL, triglycerides) 1
• Complete blood count with platelets 1
• Viral hepatitis serologies (HBV, HCV) 1
• HIV testing 1
• Autoimmune markers (ANA, ASMA, immunoglobulins) 1

Extended Testing (Based on Clinical Suspicion)

• Ferritin and transferrin saturation 1
• Tests for celiac disease and thyroid function 1
• Tests for rare liver diseases when indicated:
  • Alpha-1 antitrypsin deficiency
  • Wilson's disease (ceruloplasmin)
  • Autoimmune hepatitis panel 1

Imaging Studies

• Ultrasound is the first-line imaging modality to detect hepatic steatosis 2
• Consider advanced imaging in selected cases:
  • Transient elastography (FibroScan) to assess fibrosis 1
  • MR elastography for more accurate fibrosis assessment in obese patients 1

Non-Invasive Fibrosis Assessment

• Calculate fibrosis risk scores for all NAFLD patients 1:
  • NAFLD Fibrosis Score (NFS)
  • FIB-4 index
  • Enhanced Liver Fibrosis (ELF) test
  • FibroTest/FibroSure

Liver Biopsy Indications

• Inability to exclude significant fibrosis (≥F2) by non-invasive testing 1
• Patients with metabolic syndrome and persistently elevated liver enzymes 1
• When competing etiologies of liver disease cannot be excluded 1
• High-risk patients with diabetes or obesity with abnormal liver tests 1

Cardiovascular Risk Assessment

• All NAFLD patients should receive comprehensive cardiovascular disease workup 1
• Consider stress testing or cardiac imaging in high-risk patients 1

Monitoring Recommendations

• NAFL patients without worsening metabolic risk factors: monitor every 2-3 years 1
• NASH and/or fibrosis patients: monitor annually 1
• NASH cirrhosis: monitor every 6 months 1
• Liver biopsy may be repeated after 5 years if clinically indicated 1

Common Pitfalls to Avoid

• Attributing elevated liver enzymes solely to obesity without excluding other causes 2
• Failing to establish a reliable baseline ALT (average of two measurements at least 2 weeks apart) 2
• Neglecting to assess alcohol consumption accurately (use validated questionnaires) 1
• Overlooking the need for liver biopsy in high-risk patients with inconclusive non-invasive testing 3
• Inadequate screening for cardiovascular disease, which is a major cause of mortality in NAFLD 1

The diagnostic approach to NASHLD requires systematic evaluation of metabolic risk factors and liver disease severity. While non-invasive tests can help stratify patients, liver biopsy remains the definitive method for diagnosing NASH, grading disease severity, and staging fibrosis 3.