From the Guidelines
Acute elevations in aspartate aminotransferase (AST) are commonly caused by liver injury, but can also result from damage to other tissues containing this enzyme, with the most frequent causes including viral hepatitis, alcoholic liver disease, and drug-induced liver injury, as noted in the most recent study 1. The causes of acute AST elevation can be broadly categorized into hepatocellular and non-hepatocellular causes.
- Hepatocellular causes include:
- Viral hepatitis (particularly hepatitis A, B, and C) 1
- Alcoholic liver disease 1
- Drug-induced liver injury from medications like acetaminophen, statins, antibiotics, and herbal supplements 1
- Nonalcoholic fatty liver disease, especially during flares 1
- Ischemic hepatitis from reduced liver blood flow during shock or heart failure 1
- Autoimmune hepatitis, Wilson's disease, hemochromatosis, and alpha-1 antitrypsin deficiency 1
- Non-hepatocellular causes include:
- Muscle injury from trauma, seizures, or rhabdomyolysis, which releases AST from damaged muscle cells 1
- Biliary obstruction from gallstones or tumors, which typically causes more modest elevations in AST 1 The pattern of AST elevation relative to other liver enzymes like ALT can help determine the cause, with an AST/ALT ratio greater than 2 suggesting alcoholic liver disease, as noted in 1. The timing, magnitude of elevation, and associated symptoms provide important diagnostic clues when evaluating acute AST elevation, and a thorough history and physical examination, along with laboratory tests and imaging studies, are essential for determining the underlying cause of AST elevation, as recommended in 1.
From the Research
Causes of Acute AST Elevation
- The differential diagnosis of an increase in aspartate aminotransferase (AST) level often includes ischemic hepatitis, acute viral hepatitis, and drug-induced liver injury (DILI) 2.
- Non-hepatic causes of raised AST include polymyositis, acute muscle injury, acute myocardial infarction, and hypothyroidism 3.
- Skeletal muscle damage, cardiac muscle damage, and hematologic disorder are common etiologies of markedly elevated AST levels > 400 U/L due to non-hepatic causes 4.
- The magnitude of the peak AST level significantly correlates with 30-day mortality, with higher peak AST levels associated with increased mortality 4.
- The AST/ALT ratio can be used to screen for liver diseases and has been found to be higher in patients with ST-segment elevation myocardial infarction (STEMI) than in non-ST-segment elevation myocardial infarction (NSTEMI) patients 5.
Common Etiologies
- Ischemic hepatitis
- Acute viral hepatitis (typically hepatitis A and hepatitis B)
- Drug-induced liver injury (DILI)
- Skeletal muscle damage
- Cardiac muscle damage
- Hematologic disorder
- Polymyositis
- Acute muscle injury
- Acute myocardial infarction
- Hypothyroidism
Diagnostic Considerations
- Obtain a complete history regarding risk factors for viral hepatitis, substance abuse, and request investigations accordingly 3.
- The AST/ALT ratio can be used to predict coronary occlusion without age difference 5.
- Peak AST level and etiology significantly affect the survival rate in patients with markedly elevated AST levels > 400 U/L due to non-hepatic causes 4.