From the Guidelines
Elevated alkaline phosphatase (ALP) levels can be caused by various conditions, including liver diseases such as bile duct obstruction, hepatitis, and cirrhosis, as well as bone diseases like Paget's disease and bone metastases, and other conditions like pregnancy and certain cancers. The causes of elevated ALP can be broadly categorized into liver-related and non-liver related causes. Liver-related causes include cholestatic liver diseases, such as primary biliary cholangitis, primary sclerosing cholangitis, and intrahepatic or extrahepatic bile duct obstruction, as well as other liver conditions like hepatitis, cirrhosis, and liver cancer 1. Non-liver related causes include bone diseases like Paget's disease, bone metastases, and fracture healing, as well as other conditions like pregnancy, certain cancers, and hyperthyroidism.
Some key points to consider when evaluating elevated ALP levels include:
- The pattern of elevation, along with other laboratory findings and clinical symptoms, helps determine the underlying cause
- Measurements of gamma-glutamyl transferase (GGT) can help indicate whether elevated ALP is of hepatic or non-hepatic origin
- Imaging studies, such as magnetic resonance cholangiopancreaticography (MRCP), may be necessary to diagnose conditions like primary sclerosing cholangitis (PSC) 1
- A diagnosis of PSC should be considered in patients with elevated serum markers of cholestasis, normal high-quality cholangiography, and compatible histology of PSC, particularly in those with concomitant inflammatory bowel disease (IBD) 1
In terms of diagnosis, additional tests such as GGT, liver function tests, bone scans, or imaging studies may be necessary to pinpoint the specific cause of elevated ALP levels. The choice of diagnostic test will depend on the clinical presentation and suspected underlying cause of the elevated ALP. For example, if a liver-related cause is suspected, imaging studies like MRCP may be useful, while if a bone-related cause is suspected, bone scans or other imaging studies may be more appropriate. Overall, a thorough evaluation, including laboratory tests and imaging studies, is necessary to determine the underlying cause of elevated ALP levels and guide appropriate management.
From the Research
Causes of Elevated Alkaline Phosphatase (ALP)
The causes of elevated ALP levels can be varied and include:
- Underlying malignancy, with the most common being infiltrative intrahepatic malignancy, bony metastasis, and both hepatic and bone metastasis 2
- Bone disease, such as Paget's disease of bone, which can cause abnormal bone remodeling leading to elevated ALP levels 3, 4
- Unsuspected parenchymal liver disease, which can be a cause of elevated ALP levels in some patients 2
- Non-malignant infiltrative liver disease, which can also contribute to elevated ALP levels 2
- Sepsis, which can cause extremely high elevations of ALP, often with a normal bilirubin level 3
- Biliary obstruction, either malignant or benign, which can lead to elevated ALP levels 3
- AIDS, which can be associated with elevated ALP levels due to various opportunistic infections or medications 3
- High bone turnover, which is a common cause of elevated ALP levels in postmenopausal women 5
- Liver disease, such as alcohol-induced hepatitis, which can cause a transient increase in serum ALP levels, even in patients with hypophosphatasia 6
- Other disorders, such as diffuse liver metastases, benign intrahepatic disease, and drug-induced cholestasis, which can also contribute to elevated ALP levels 2, 3