From the Guidelines
Elevated alkaline phosphatase (ALP) with normal other liver enzymes is most likely indicative of a cholestatic condition, and I recommend a comprehensive evaluation starting with a detailed medical history and physical examination, followed by measurements of gamma-glutamyl transferase (GGT) and imaging studies of the biliary tree, as suggested by the most recent guidelines 1. This approach is based on the understanding that ALP is produced mainly in the liver and is present in the canalicular membrane of the hepatocyte, but can also be found in bone and other tissues, making its elevation nonspecific but suggestive of cholestasis when GGT is also elevated 1. Key considerations in the differential diagnosis include:
- Cholestatic liver disease, such as primary biliary cholangitis or primary sclerosing cholangitis
- Intrahepatic or extrahepatic bile duct obstruction, which could be due to choledocholithiasis, malignant obstruction, or other causes
- Bone disease, such as Paget’s disease, which can also cause elevated ALP
- Drug-induced cholestasis, which should be considered based on the patient’s medication history Given the nonspecific nature of ALP elevation, concomitantly elevated GGT can help confirm that the elevated ALP originates from the liver and indicates cholestasis, guiding further diagnostic steps such as imaging of the biliary tree 1. The choice of imaging modality may depend on the clinical context and the suspected etiology of the cholestasis, with ultrasound being a reasonable initial choice, and MRCP potentially offering more detailed information about the biliary tree if needed 1.
From the Research
Elevated Alkaline Phosphatase and Normal Liver Enzymes
- Elevated alkaline phosphatase (ALP) with normal liver enzymes can be an indicator of various conditions, including cholestasis 2.
- Cholestasis is characterized by an elevated serum ALP and gamma-glutamyltransferase (GGT) disproportionate to elevation of aminotransferase enzymes 3.
- The diagnostic workup for elevated ALP includes visualization of the biliary tree by cholangiography and evaluation of liver histology 3.
Relationship between Alkaline Phosphatase and Gamma-Glutamyltransferase
- Serum gamma-glutamyl transpeptidase (GGT) activity correlates closely with the activities of alkaline phosphatase (ALP) and 5'-nucleotidase (5NT) in various forms of liver disease 4.
- GGT is generally increased to a greater extent than ALP and 5NT, making it the most sensitive indicator of biliary-tract disease 4.
- The ratio of GGT to 5NT can be useful in differentiating between intrahepatic and extrahepatic cholestasis 5.
Clinical Significance of Enzyme Patterns
- Enzyme patterns, including ALP, GGT, and 5NT, can provide useful information in the diagnosis of cholestasis 5, 2.
- The combination of these enzymes can help in identifying the underlying cause of elevated ALP and normal liver enzymes 6.
- However, it is essential to consider the effects of certain drugs on serum enzyme activities, such as phenytoin and barbiturates, which can elevate GGT without any evidence of liver disease 4.