What does it mean to have elevated Alanine Transaminase (ALT) and Aspartate Transaminase (AST) levels?

Elevated ALT and AST: Evaluation and Management

Elevated ALT and AST levels indicate liver injury that requires a systematic evaluation to identify the underlying cause, starting with noninvasive serologic tests and appropriate imaging studies. 1

Understanding Elevated Liver Enzymes

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are biomarkers for liver damage, with ALT being more specific for liver injury while AST is also present in cardiac tissue, skeletal muscle, and erythrocytes 2. Elevations are classified as:

• Mild: <5× upper limit of normal (ULN)
• Moderate: 5-10× ULN
• Severe: >10× ULN 1

Diagnostic Approach

Initial Laboratory Evaluation

• Complete liver panel including:
  • Bilirubin
  • Alkaline phosphatase
  • GGT
  • Albumin
  • Prothrombin time/INR 1

Viral Hepatitis Screening

• Hepatitis A: Anti-HAV IgM
• Hepatitis B: HBsAg, Anti-HBc IgM
• Hepatitis C: HCV antibody 1

Alcohol Assessment

• Calculate AST:ALT ratio (≥2 strongly suggests alcoholic liver disease)
• Check GGT levels 1

Imaging

• Abdominal ultrasound as first-line imaging to:
  • Assess liver structure
  • Rule out biliary obstruction
  • Evaluate for fatty infiltration 1

Fibrosis Assessment

• FIB-4 score as initial assessment
• Follow with liver elastography if fibrosis is suspected 1

Additional Testing Based on Clinical Suspicion

• Autoimmune markers (ANA, ASMA, immunoglobulin levels) for suspected autoimmune hepatitis
• Medication review (prescription, OTC, supplements) to identify potential hepatotoxins
• Consider testing for less common causes:
  • Hemochromatosis
  • α1-antitrypsin deficiency
  • Wilson's disease
  • Celiac disease
  • Thyroid disorders
  • Muscle disorders 1, 3

Common Causes of Elevated Liver Enzymes

1. Nonalcoholic fatty liver disease (NAFLD) - Most common cause worldwide 3
2. Alcohol-related liver disease - AST:ALT ratio ≥2 is suggestive 1
3. Medication-induced liver injury - Can occur with various medications, including psychiatric medications 4
4. Viral hepatitis - Hepatitis B and C 1, 3
5. Macro-AST - A benign condition causing isolated AST elevation; diagnosed with PEG precipitation test 5

Management Strategies

Lifestyle Modifications

• Mediterranean diet
• Regular exercise
• Weight loss for patients with metabolic risk factors 1

Alcohol Cessation

• Complete cessation essential, especially with advanced fibrosis or cirrhosis 1

Medication Management

• Identify and discontinue potential hepatotoxic medications
• For medications known to affect liver enzymes:
  • Monitor CBC and LFTs within first 1-2 months of usage
  • Continue monitoring every 3-4 months
  • Consider dose reduction or temporary discontinuation for clinically relevant elevations 1

Severe Elevations Management

• For elevations >10× ULN or signs of acute liver failure:
  • Initiate IV fluids
  • Correct coagulopathy
  • For suspected acetaminophen toxicity, initiate N-acetylcysteine therapy without waiting for serum acetaminophen levels 1

When to Refer to Hepatology

Refer to a hepatologist if:

• Liver function tests remain elevated after 3-6 months despite interventions
• Signs of hepatic decompensation are present
• Suspected autoimmune hepatitis
• ALT elevation >5× ULN
• Persistent elevation >6 months despite interventions
• Conflicting clinical, laboratory, and imaging findings
• Development of jaundice or elevated bilirubin with elevated transaminases 1

Important Considerations

• Isolated AST elevation may be due to non-hepatic causes like muscle disorders or macro-AST 5
• Mild hypertransaminasemia (less than 5× normal) is common in primary care and may have benign or serious causes 3
• Elevated liver enzymes can persist long after the initial insult, as seen in burn patients 6
• AST:ALT ratio ≥1 with chronic HCV has high specificity for cirrhosis 1