From the Guidelines
To assess the cause of elevated alkaline phosphatase (ALP), I recommend ordering a comprehensive panel of tests including gamma-glutamyl transferase (GGT), bilirubin (total and direct), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and a hepatitis panel, as the most recent and highest quality study suggests that these tests are essential in distinguishing between hepatobiliary causes and bone disorders 1.
Initial Workup
The initial workup should include:
- Gamma-glutamyl transferase (GGT) to determine if the elevation is of hepatic or nonhepatic origin
- Bilirubin (total and direct) to assess for jaundice
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) to evaluate for hepatocellular injury
- A hepatitis panel to rule out viral hepatitis
Additional Tests
Additional tests that may be ordered include:
- Calcium, phosphate, parathyroid hormone (PTH), and vitamin D levels to evaluate for bone disorders
- Isoenzyme fractionation of ALP to determine the source of elevation (liver, bone, intestine, or placenta) if the initial workup is inconclusive
Imaging Studies
Imaging studies should include:
- Abdominal ultrasound to assess the liver and biliary tract
- Bone scans if bone pathology is suspected
- Magnetic resonance cholangiopancreaticography (MRCP) if primary sclerosing cholangitis (PSC) is suspected, as it has a high sensitivity and specificity for diagnosing PSC 1
Special Considerations
In cases where malignancy is suspected, tumor markers and more advanced imaging like CT or MRI may be warranted. It is also important to consider the patient's clinical history and medications, as certain medications can cause elevated ALP levels 1.
From the Research
Tests to Order for Elevated ALP
To assess the cause of elevated alkaline phosphatase (ALP) levels, the following tests can be ordered:
- Viral hepatitis panel (hepatitis A, B, and C) to rule out viral hepatitis as a cause of hepatocellular injury or cholestasis 2
- Assessment for nonalcoholic fatty liver disease and alcoholic liver disease to evaluate for potential causes of hepatocellular injury or cholestasis 2
- Screening for hereditary hemochromatosis, autoimmune hepatitis, Wilson's disease, and alpha-1 antitrypsin deficiency to evaluate for potential genetic or autoimmune causes of hepatocellular injury or cholestasis 2
- Testing for primary biliary cholangitis and primary sclerosing cholangitis to evaluate for potential causes of cholestatic injury 2
- Fractionation of total bilirubin to direct and indirect bilirubin fractions to determine if the elevation is due to conjugated or unconjugated bilirubin 2
- Liver biopsy may be considered if serologic testing and imaging fail to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible 2
Additional Considerations
- A thorough history of prescribed and over-the-counter medicines should be sought to evaluate for potential drug-induced causes of hepatocellular injury or cholestasis 2
- Imaging studies may be ordered to evaluate for potential structural causes of cholestasis or hepatocellular injury, such as gallstones or liver masses 2