From the Guidelines
Elevated alkaline phosphatase (ALP) levels can be caused by a variety of conditions, including liver diseases such as primary biliary cholangitis, primary sclerosing cholangitis, and cholestatic liver disease, as well as bone diseases like Paget's disease and bone metastases, and should be further investigated to determine the underlying cause. The first step is to determine if the elevation is isolated or accompanied by other abnormal liver tests. If isolated, consider checking bone-specific ALP or gamma-glutamyl transferase (GGT) to help distinguish between bone and liver sources, as suggested by 1. Common liver causes include biliary obstruction, cholestasis, certain medications, and liver diseases like primary biliary cholangitis. Bone-related causes include Paget's disease, bone growth in children, healing fractures, and bone metastases, which are also mentioned in 1. Initial workup should include a comprehensive history, physical examination, and additional laboratory tests such as bilirubin, transaminases, and imaging studies like ultrasound or CT scan of the liver if liver pathology is suspected.
Some key points to consider in the evaluation of elevated ALP include:
- The presence of concomitantly elevated GGT can help confirm that an elevated ALP originates from the liver and indicates cholestasis, as noted in 1.
- Choledocholithiasis is the most common cause of extrahepatic biliary obstruction and elevated ALP of liver origin, as mentioned in 1.
- Infiltrative liver diseases such as sarcoidosis, amyloidosis, and hepatic metastases may also lead to intrahepatic cholestasis and elevated ALP, as discussed in 1.
- Magnetic resonance cholangiopancreaticography (MRCP) can be used as a diagnostic test for primary sclerosing cholangitis, with a pooled sensitivity and specificity of 86% and 94%, respectively, as reported in 1.
Treatment depends entirely on the underlying cause - for example, ursodeoxycholic acid for primary biliary cholangitis or bisphosphonates for Paget's disease. Mild, isolated ALP elevations (less than 2-3 times the upper limit of normal) without symptoms may sometimes be monitored without immediate intervention, but persistent or significant elevations warrant thorough evaluation to identify and address the root cause, as suggested by the most recent and highest quality study 1.
From the Research
Causes of Elevated Alkaline Phosphatase (ALP) Levels
Elevated ALP levels can be caused by a variety of factors, including:
- Sepsis, which can cause extremely high ALP levels, even with normal bilirubin levels 2
- Malignant obstruction, which is a common cause of extremely high ALP levels 2
- AIDS, which can cause elevated ALP levels due to various opportunistic infections or medications 2
- Bone disease, such as Paget's disease or bone metastasis, which can cause elevated ALP levels 3, 4
- Liver disease, such as liver metastasis or parenchymal liver disease, which can cause elevated ALP levels 3, 4
- Certain types of cancer, such as colorectal, pancreatic, or lung cancer, which can cause elevated ALP levels 4, 5
- Defective elimination of ALP from the serum, which can contribute to unexplained elevations of serum ALP 6
Specific Causes of Elevated ALP Levels
Some specific causes of elevated ALP levels include:
- Biliary obstruction, which can cause elevated ALP levels due to liver damage or disease 2
- Bone metastasis, which can cause elevated ALP levels due to bone disease 3, 4
- Infiltrative intrahepatic malignancy, which can cause elevated ALP levels due to liver disease 3
- Sepsis or fungal infections, which can cause elevated ALP levels due to systemic inflammation or infection 2
- Certain medications, such as Dilantin, which can cause elevated ALP levels due to liver damage or disease 2
Clinical Significance of Elevated ALP Levels
Elevated ALP levels can have significant clinical implications, including: