Testing for Hepatocellular Injury

Aspartate Aminotransferase (AST)

1. AST is a cytoplasmic enzyme in liver, muscle, RBC's and other locations

2. Released from damaged cells; serum levels peak 24-36 hr after injury and normalize at 3-6 days if injury isn't ongoing

3. Highest elevations occur in viral hepatitis and hepatotoxicity (10-20 times the upper reference limit)

4. Mild-to-moderate (3-10 fold) elevations occur in chronic hepatitis, active cirrhosis, chronic passive congestion, drug-induced injury, metastatic tumor, biliary disease and a number of other conditions.

5. Cardiac and skeletal muscle injury will also produce substantial AST elevations.

Alanine Aminotransferase (ALT)

1. More specific for the liver than AST, but also present in kidney and muscle

2. Used to confirm that AST elevations are of liver origin (e.g., elevation of both AST and ALT strongly suggest hepatocellular injury)

3. The time course of ALT elevations in liver disease is shown below; AST would show a similar overall time course (though the ratio of the AST and ALT varies with disease and from patient to patient, as described in the next section)

AST/ALT Ratio

1. Viral heptitis, mononucleosis, and acute hepatotoxicity typically show elevations in ALT that are equal to or greater than AST elevations (AST/ALT less than or equal to 1.0)

2. ALT is elevated to a lesser degree than AST in alcoholic liver disease and cirrhosis, passive congestion, bile duct obstruction, or metastatic tumor to the liver (AST/ALT greater than 1.0)

3. These are rules of thumb--substantial minorities of patients deviate from them, making the AST/ALT ratio of limited usefulness in the diagnosis of individual patients (though it may be helpful in suggesting the next appropriate step in the workup)