What are the next steps if my Aspartate Aminotransferase (AST) is elevated?

Evaluation and Management of Elevated AST

When AST is elevated, a systematic diagnostic approach is needed to identify the underlying cause, with initial evaluation focusing on the pattern and degree of elevation, followed by targeted testing based on clinical context and risk factors. 1

Initial Assessment of Elevated AST

Pattern and Degree of Elevation

• Mild elevation (<2× upper limit of normal): Often non-specific, may not indicate significant liver disease
• Moderate elevation (2-5× ULN): Warrants further investigation
• Severe elevation (>5× ULN): Suggests significant liver injury requiring prompt evaluation
• Extreme elevation (>20× ULN): Indicates acute severe liver injury (viral, drug-induced, ischemic) 1

AST/ALT Ratio Assessment

• AST/ALT ratio >2: Highly suggestive of alcoholic liver disease (ALD) 2
• AST/ALT ratio >3: Even more specific for ALD 2
• AST <500 IU/L or ALT <200 IU/L: Typical for alcoholic hepatitis (higher values suggest another etiology) 2
• AST/ALT ratio >3 in acute cases: May indicate muscle injury, but this ratio approaches 1 after a few days 3

Common Causes of Elevated AST

1. Liver-related causes:

   • Nonalcoholic fatty liver disease (NAFLD) - most common cause 4
   • Alcoholic liver disease (ALD) - most common cause 4
   • Viral hepatitis (B and C) 4
   • Drug-induced liver injury 4
   • Autoimmune hepatitis 2

2. Non-liver causes:

   • Muscle disorders/injury (exercise, polymyositis, seizures) 3
   • Hemolysis 4
   • Thyroid disorders 4
   • Celiac disease 4
   • Macro-AST (benign condition where AST binds to immunoglobulins) 5, 6, 7

Diagnostic Workup

First-line Testing

1. Complete liver panel:

   • AST, ALT, alkaline phosphatase, GGT, total and direct bilirubin 1
   • Serum albumin and prothrombin time/INR (to assess synthetic function) 1

2. Metabolic assessment:

   • Fasting lipid profile
   • Fasting glucose or A1C level
   • Blood pressure measurement
   • Waist circumference 4

3. Additional blood tests:

   • Complete blood count with platelets
   • Serum albumin, iron, total iron-binding capacity, and ferritin 4

4. Viral hepatitis screening:

   • Hepatitis B surface antigen (HBsAg)
   • Hepatitis B core antibody (anti-HBc)
   • Hepatitis C antibody (with reflex RNA testing if positive) 1

5. Imaging:

   • Abdominal ultrasound (first-line imaging test) 1

Second-line Testing (if initial evaluation inconclusive)

• Autoimmune markers (ANA, ASMA, anti-LKM)
• Ceruloplasmin (for Wilson disease)
• Alpha-1 antitrypsin level
• Polyethylene glycol (PEG) precipitation test (for macro-AST) 5, 7
• CT or MRCP if ultrasound inconclusive 1

Management Based on Diagnosis

NAFLD/Metabolic Syndrome

• Lifestyle modifications (Mediterranean diet, regular exercise, weight loss if overweight/obese) 1
• Optimize glycemic control in diabetic patients 1

Alcoholic Liver Disease

• Immediate alcohol abstinence
• Referral for alcohol use disorder treatment 1

Autoimmune Hepatitis

• Treatment with prednisolone and azathioprine for at least 2 years and for at least 12 months after normalization of transaminases 1
• Absolute indications for treatment: AST ≥10× ULN or AST ≥5× ULN with γ-globulin ≥2× ULN 2

Drug-Induced Liver Injury

• Discontinue suspected hepatotoxic medications
• For ALT/AST >3× ULN: adjust dose or discontinue medication
• For ALT/AST >5× ULN: discontinue medication and consider hepatology referral 1

Macro-AST

• Reassurance (benign condition)
• No specific treatment needed 5, 6

When to Refer to Hepatology

Urgent Referral

• ALT/AST >20× ULN
• Evidence of acute liver failure
• ALT/AST >3× ULN with total bilirubin ≥2× ULN
• Development of jaundice, abdominal pain, or fatigue 1

Non-urgent Referral

• Persistent elevation >6 months despite interventions
• Suspected autoimmune hepatitis requiring histological confirmation
• Conflicting clinical, laboratory, and imaging findings 1

Follow-up

• If initial testing suggests NAFLD and is otherwise unremarkable, trial lifestyle modification
• If elevation persists, consider hepatic ultrasonography and testing for uncommon causes 4
• Annual monitoring of liver enzymes for long-term follow-up 1

Important Caveats

• Isolated AST elevation in otherwise healthy individuals may represent macro-AST, which follows a benign course 6
• Overreaction to mild elevations should be avoided, as 2.5% of healthy individuals will have abnormal liver function tests by definition 1
• In children with isolated AST elevation, macro-AST should be considered (22% of cases in one study) 6
• AST elevations in muscle disorders typically show AST/ALT ratio >3 initially, approaching 1 after a few days 3