What tests should be ordered to diagnose alcoholic liver disease?

Diagnostic Tests for Alcoholic Liver Disease

The diagnosis of alcoholic liver disease (ALD) requires a thorough alcohol history, liver function tests showing an AST/ALT ratio >2, and appropriate imaging studies, with liver biopsy reserved for uncertain cases or when specific treatment decisions depend on histological confirmation. 1

Initial Laboratory Assessment

Essential Blood Tests

• Liver enzymes:
  • AST and ALT (AST/ALT ratio typically >2, often >3 in ALD) 1
  • AST usually 50-400 IU/L (levels >500 IU/L suggest other etiologies) 1
  • GGT (elevated in ~75% of habitual drinkers) 1
• Liver function markers:
  • Serum albumin
  • Bilirubin
  • Prothrombin time/INR 2
• Complete blood count:
  • Macrocytosis (elevated MCV)
  • Leukocytosis (in alcoholic hepatitis)
  • Thrombocytopenia (suggests portal hypertension) 1

Alcohol Biomarkers

• Traditional markers:
  • Carbohydrate-deficient transferrin (CDT) - specific but low sensitivity (25-50%) 1
  • GGT - sensitive but not specific 1
• Advanced biomarkers (preferred as they're not affected by liver disease):
  • Phosphatidylethanol (PEth) - half-life 10-14 days, high sensitivity (91%) and specificity (77%) 1
  • Urine/hair ethyl glucuronide (EtG)
  • Urine ethyl sulfate (EtS) 1

Alcohol Screening Tools

• AUDIT (Alcohol Use Disorders Identification Test) - positive if score ≥8 for men up to age 60, or ≥4 for women, adolescents, or men over 60 1
• AUDIT-C - abbreviated version, positive if score ≥4 1
• These screening tools improve detection and prediction of long-term outcomes 1

Imaging Studies

First-Line Imaging

• Ultrasonography: Detects steatosis, evaluates liver morphology, rules out biliary obstruction, identifies complications of portal hypertension 1

Additional Imaging Options

• CT scan: More specific but more expensive than ultrasound 1
• MRI: Can help distinguish alcoholic from non-alcoholic cirrhosis 1
• Elastography techniques:
  • Transient elastography (FibroScan)
  • Acoustic radiation force impulse imaging
  • Shear wave elastography
  • These methods can detect advanced fibrosis with ~95% accuracy 3

Liver Biopsy

• Indications:
  • Uncertain diagnosis or suspected mixed etiology
  • Severe alcoholic hepatitis requiring corticosteroid treatment
  • Suspected advanced fibrosis or cirrhosis when non-invasive tests are inconclusive 1
• Histological findings:
  • Steatosis (macrovesicular)
  • Hepatocyte ballooning
  • Mallory-Denk bodies
  • Neutrophilic infiltration
  • Perisinusoidal fibrosis
  • Cirrhotic nodules (in advanced disease) 1

Diagnostic Algorithm

1. Step 1: Obtain liver enzymes, function tests, and complete blood count
2. Step 2: Screen for alcohol use with validated questionnaires (AUDIT or AUDIT-C)
3. Step 3: Exclude other liver diseases with appropriate testing
4. Step 4: Perform abdominal ultrasound to assess liver morphology and rule out other causes
5. Step 5: Consider advanced fibrosis assessment with elastography
6. Step 6: Consider liver biopsy if diagnosis remains uncertain or treatment decisions depend on histology

Common Pitfalls and Caveats

• AST/ALT ratio >2 is highly suggestive of ALD but not pathognomonic 1
• Normal liver enzymes don't exclude ALD, especially in early stages 1
• Imaging studies can detect steatosis and cirrhosis but cannot distinguish between simple steatosis and steatohepatitis 1
• Conventional screening (ultrasound and routine labs) can miss up to 40% of alcoholic cirrhosis cases 3
• Biomarkers should be used in combination with clinical assessment, not in isolation 1
• Liver biopsy remains important to rule out comorbidities and confirm prognosis, especially in alcoholic hepatitis 3

Severity Assessment Tools

• Maddrey Discriminant Function (DF) - severe alcoholic hepatitis if ≥32 2
• MELD score - severe alcoholic hepatitis if >20 2
• These scores help determine prognosis and guide treatment decisions

By following this diagnostic approach, clinicians can accurately identify ALD, assess its severity, and initiate appropriate management strategies to improve patient outcomes.