From the Guidelines
Elevated AST and ALT levels are most commonly caused by liver damage or injury, with the most frequent causes including nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease, viral hepatitis, and medication-induced liver injury, as reported in the 2023 study by the Journal of the American College of Radiology 1. The causes of elevated AST and ALT can be broadly categorized into hepatocellular and non-hepatocellular causes. Hepatocellular causes include:
- Nonalcoholic fatty liver disease (NAFLD)
- Alcoholic liver disease
- Viral hepatitis (types A, B, C, D, and E)
- Medication-induced liver injury
- Autoimmune hepatitis
- Hemochromatosis
- Wilson's disease
- Alpha-1 antitrypsin deficiency Non-hepatocellular causes include:
- Muscle damage (rhabdomyolysis, muscle trauma, or strenuous exercise)
- Heart conditions (heart attacks)
- Thyroid disease
- Hemolysis
- Myopathy The severity of elevation often correlates with the extent of tissue damage, with ALT being more specific to liver injury while AST is found in multiple tissues. When these enzymes are elevated, it's essential to identify the underlying cause through additional testing, as treatment depends on addressing the specific condition causing the abnormality, as recommended in the 2024 review article by Alimentary Pharmacology and Therapeutics 1. Some key tests to consider in the evaluation of elevated AST and ALT include:
- Serum creatine kinase to rule out muscle injury
- Hepatitis A, B, C, and E testing to diagnose viral hepatitis
- Autoantibody and immunoglobulin testing to diagnose autoimmune hepatitis
- Hepatobiliary imaging (ultrasonography, CT scan, MRI) to evaluate for biliary obstruction, pancreatitis, or hepatic metastasis
- Liver biopsy to determine the pattern and severity of liver injury.
From the Research
Causes of Elevated AST and ALT
Elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) can be caused by various factors, including:
- Hepatocellular injury, which is defined as disproportionate elevation of AST and ALT levels compared with alkaline phosphatase levels 2
- Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD), which are the most common causes of liver disease and cirrhosis worldwide 3
- Viral hepatitis, such as hepatitis B and C, which can cause hepatic steatosis and elevate liver enzymes 4
- Metabolic syndrome, including obesity, type 2 diabetes mellitus, and dyslipidemia, which can contribute to the development of NAFLD and elevate liver enzymes 5
- Other factors, such as unhealthy dietary habits, pre-existing metabolic disturbances, and genetic factors, which can also contribute to the development of NAFLD and elevate liver enzymes 5
Laboratory Features
The ratio of AST to ALT can help differentiate between NAFLD and ALD, with a ratio of < 1 being more frequent in NAFLD than ALD in the absence of cirrhosis 3.
- Elevated ALT levels have been associated with increased liver-related mortality 2
- A true healthy normal ALT level ranges from 29 to 33 IU/l for males and 19 to 25 IU/l for females, and levels above this should be assessed 2
Evaluation and Diagnosis
The evaluation of hepatocellular injury includes testing for viral hepatitis, assessment for NAFLD and ALD, screening for hereditary hemochromatosis, autoimmune hepatitis, Wilson's disease, and alpha-1 antitrypsin deficiency, as well as a history of prescribed and over-the-counter medicines 2
- A liver biopsy may be considered when serologic testing and imaging fail to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible 2