What is the appropriate workup for a patient with elevated Alanine Transaminase (ALT) and Aspartate Transaminase (AST) levels, with normal Alkaline Phosphatase (ALP) and Gamma-Glutamyl Transferase (GGT) levels?

From the Guidelines

When evaluating a patient with elevated ALT and AST but normal ALP and GGT, a thorough history and physical examination focusing on risk factors for liver disease should be performed, followed by a standard liver aetiology screen including abdominal ultrasound scan, hepatitis B surface antigen, hepatitis C antibody, anti-mitochondrial antibody, anti-smooth muscle antibody, antinuclear antibody, serum immunoglobulins, simultaneous serum ferritin and transferrin saturation, as recommended by the guidelines on the management of abnormal liver blood tests 1.

Initial Evaluation

The initial evaluation should include a review of the patient's medical history, current medical condition, and previous laboratory results, as emphasized in Recommendation 2 of the guidelines 1. This will help determine the clinical significance of the abnormal liver blood test results.

Laboratory Tests

Additional laboratory tests should be ordered, including:

• Complete blood count
• Comprehensive metabolic panel
• Coagulation studies
• Viral hepatitis serologies (hepatitis A, B, and C)
• Autoimmune markers (ANA, anti-smooth muscle antibody, anti-LKM)
• Iron studies
• Ceruloplasmin (for Wilson's disease)
• Alpha-1 antitrypsin levels
• Lipid profile

Imaging Studies

Imaging studies should include an abdominal ultrasound to evaluate liver structure and rule out biliary obstruction, as recommended in Recommendation 5 of the guidelines 1.

Considerations

Metabolic causes such as non-alcoholic fatty liver disease (NAFLD) should be considered, as it is the most common cause of isolated aminotransferase elevation in developed countries. Assess for alcohol use, medication history (including over-the-counter drugs and supplements), and family history of liver disease.

Monitoring and Treatment

Liver enzymes should be monitored every 3-6 months during the diagnostic process and after initiating treatment. Lifestyle modifications including weight loss, exercise, and alcohol cessation are often first-line interventions, while specific therapy depends on the underlying etiology. The pattern of predominantly elevated aminotransferases with normal alkaline phosphatase suggests hepatocellular injury rather than cholestatic disease.

Further Evaluation

If the diagnosis remains unclear after initial workup, consider liver biopsy, as recommended in the guidelines for patients with chronic HCV viremia and either normal or abnormal serum ALT levels 1.

From the Research

Appropriate Workup for Elevated ALT and AST Levels

The appropriate workup for a patient with elevated Alanine Transaminase (ALT) and Aspartate Transaminase (AST) levels, with normal Alkaline Phosphatase (ALP) and Gamma-Glutamyl Transferase (GGT) levels, involves a series of steps to determine the underlying cause of the elevation.

• Evaluate the patient's medical history, including alcohol consumption, medication use, and any underlying medical conditions 2, 3.
• Perform a physical examination to look for signs of liver disease, such as jaundice or abdominal tenderness 2.
• Order additional laboratory tests, such as:
  • Viral hepatitis panel to rule out hepatitis A, B, or C 2.
  • Autoimmune hepatitis panel to rule out autoimmune hepatitis 3.
  • Wilson's disease testing to rule out Wilson's disease 3.
  • Alpha-1 antitrypsin deficiency testing to rule out alpha-1 antitrypsin deficiency 3.
• Consider imaging studies, such as ultrasound or CT scan, to evaluate the liver and bile ducts 4.
• If the patient has a history of alcohol consumption, consider testing for alcoholic liver disease, including the AST/ALT ratio and GGT levels 2.

Differential Diagnosis

The differential diagnosis for elevated ALT and AST levels with normal ALP and GGT levels includes:

• Viral hepatitis 2.
• Alcoholic liver disease 2.
• Non-alcoholic fatty liver disease (NAFLD) 3.
• Autoimmune hepatitis 3.
• Wilson's disease 3.
• Alpha-1 antitrypsin deficiency 3.
• Drug-induced liver injury 3, 5.

Laboratory Tests

Laboratory tests that may be useful in evaluating elevated ALT and AST levels include:

• AST/ALT ratio: an elevated ratio may indicate alcoholic liver disease 2.
• GGT: an elevated level may indicate cholestasis or alcoholic liver disease 2, 3.
• ALP: an elevated level may indicate cholestasis or bone disease 4.
• Viral hepatitis panel: to rule out hepatitis A, B, or C 2.
• Autoimmune hepatitis panel: to rule out autoimmune hepatitis 3.
• CK: to evaluate for muscle injury 5.