From the Guidelines
AST and ALT elevations are typically indicative of liver damage or injury, with common causes including liver diseases such as viral hepatitis, alcoholic liver disease, and non-alcoholic fatty liver disease, as well as medications and muscle damage, as noted in the most recent study 1. The causes of AST and ALT elevation can be broadly categorized into liver diseases, medications, and non-hepatic causes. Liver diseases that can cause elevations include:
- Viral hepatitis (A, B, C)
- Alcoholic liver disease
- Non-alcoholic fatty liver disease (NAFLD)
- Autoimmune hepatitis
- Hemochromatosis
- Wilson's disease
- Alpha-1 antitrypsin deficiency Medications that can cause elevations include:
- Acetaminophen overdose
- Statins
- Antibiotics like isoniazid
- Certain antiepileptics Non-hepatic causes of AST elevation include:
- Muscle damage, such as rhabdomyolysis, muscle trauma, or strenuous exercise
- Heart conditions, such as myocardial infarction
- Biliary obstruction from gallstones or tumors
- Certain infections beyond hepatitis The pattern of elevation, including the AST:ALT ratio, can provide diagnostic clues, with alcoholic liver disease typically showing an AST:ALT ratio >2:1, as noted in 1 and 1. However, the most recent study 1 provides a more comprehensive overview of the causes of AST and ALT elevation, highlighting the importance of considering both hepatic and non-hepatic causes. Key points to consider when evaluating AST and ALT elevations include:
- The degree of elevation, with mild elevations suggesting chronic conditions and severe elevations indicating acute injury
- The pattern of elevation, including the AST:ALT ratio
- The presence of other laboratory abnormalities, such as elevated gamma glutamyl transpeptidase (GGT) or carbohydrate deficient transferrin (CDT)
- The patient's medical history, including alcohol consumption and medication use.
From the Research
Causes of AST and ALT Elevation
- Hepatocellular injury, which is defined as disproportionate elevation of AST and ALT levels compared with alkaline phosphatase levels 2
- Cholestatic injury, which is defined as disproportionate elevation of alkaline phosphatase level as compared with AST and ALT levels 2
- Viral hepatitis A, B, and C 2
- Nonalcoholic fatty liver disease and alcoholic liver disease 2
- Hereditary hemochromatosis, autoimmune hepatitis, Wilson's disease, and alpha-1 antitrypsin deficiency 2
- Ischemic hepatitis, acute viral hepatitis, and drug-induced liver injury (DILI) 3
- Myocardial infarction, as seen in a 79-year-old woman who developed elevated serum transaminases shortly after having a myocardial infarction 4
- Obesity, as seen in a 40-year-old woman who presented with increased ALT and AST levels in the absence of physical symptoms 4
- Primary biliary cholangitis and primary sclerosing cholangitis, which should be tested for when an alkaline phosphatase elevation is determined to be of hepatic origin 2
Diagnostic Approach
- Evaluation of hepatocellular injury includes testing for viral hepatitis A, B, and C, assessment for nonalcoholic fatty liver disease and alcoholic liver disease, screening for hereditary hemochromatosis, autoimmune hepatitis, Wilson's disease, and alpha-1 antitrypsin deficiency 2
- A history of prescribed and over-the-counter medicines should be sought 2
- A liver biopsy may be considered when serologic testing and imaging fails to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible 2
- Histopathologic findings on a liver biopsy or a liver explant may help identify the underlying etiology or provide an important direction for further clinical, laboratory and radiographical investigation 5