What labs should be ordered for a patient with elevated alkaline phosphatase (alk/phos) levels?

From the Guidelines

For a patient with elevated alkaline phosphatase (ALP) levels, I recommend ordering a comprehensive panel of follow-up tests, including liver function tests (AST, ALT, GGT, bilirubin), hepatitis serologies, abdominal ultrasound or imaging, and bone-specific tests, to determine the underlying cause, as elevated ALP can originate from various sources, including liver disease, bone disorders, and other conditions 1. When evaluating a patient with elevated ALP levels, it is essential to consider the potential sources of the elevation, including liver and bone disease.

• Liver function tests, such as AST, ALT, GGT, and bilirubin, can help determine if the elevation is of hepatic origin 1.
• Hepatitis serologies and tests for primary biliary cholangitis (anti-mitochondrial antibodies) and primary sclerosing cholangitis can also be useful in evaluating liver disease 1.
• Bone-specific tests, including calcium, phosphorus, parathyroid hormone (PTH), and vitamin D levels, can help determine if the elevation is of bone origin 1.
• Additional relevant tests, such as complete blood count, renal function tests, and testing for pregnancy, malignancy markers, or thyroid function, may also be necessary to narrow the differential diagnosis and guide management 1. The pattern of elevation in conjunction with other laboratory abnormalities will help guide appropriate management, and the initial workup should be tailored based on the patient's clinical presentation, age, medical history, and any accompanying symptoms 1.
• Fractionating alkaline phosphatase into its liver, bone, and intestinal isoenzyme fractions can also be informative in determining the source of the elevation 1.
• Glutamate dehydrogenase (GLDH) levels can provide further supporting evidence that aminotransferase elevations are of hepatic origin and potentially indicate hepatic mitochondrial injury 1.

From the Research

Labs for Elevated Alk/Phos

To evaluate a patient with elevated alkaline phosphatase (alk/phos) levels, the following labs should be ordered:

• Liver function tests, including:
  • AST and ALT to evaluate hepatocellular injury 2
  • GGT to confirm the hepatic origin of the alkaline phosphatase elevation 3, 4
  • Bilirubin levels to evaluate for hyperbilirubinemia 3, 2
• Tests to distinguish between extrahepatic and intrahepatic cholestasis, such as:
  • Abdominal ultrasound to evaluate the biliary system 3
  • Cholangiography to visualize the biliary tree 5
• Tests to evaluate for underlying causes of elevated alk/phos, such as:
  • Viral hepatitis serologies (e.g. hepatitis A, B, and C) 2
  • Autoimmune hepatitis panel 2
  • Wilson's disease testing 2
  • Alpha-1 antitrypsin deficiency testing 2
  • Primary biliary cholangitis and primary sclerosing cholangitis testing 2
• Other tests as indicated by the patient's clinical presentation and medical history, such as:
  • Iron levels to evaluate for hemochromatosis 3, 2
  • Medication history to evaluate for drug-induced liver injury 4, 2

Additional Considerations

• A liver biopsy may be considered if serologic testing and imaging fail to elucidate a diagnosis, or if multiple diagnoses are possible 2
• Defective enzyme elimination may play a role in the pathogenesis of serum alkaline phosphatase elevations, and should be considered in cases of unexplained elevations 6