From the Guidelines
Elevated alkaline phosphatase (ALP) levels can be caused by a variety of conditions, including liver diseases such as cholestasis, biliary obstruction, and cirrhosis, as well as bone diseases like Paget's disease and fracture healing, and should be further investigated to determine the underlying cause. The first step in evaluating elevated ALP levels is to confirm whether the elevation is isolated or accompanied by other abnormal liver enzymes, as this can help differentiate between liver and bone sources 1. If the elevation is isolated, consider ordering bone-specific ALP or gamma-glutamyl transferase (GGT) to further differentiate between bone and liver sources.
Common Causes of Elevated ALP
- Liver causes: biliary obstruction, cholestasis, certain medications, and liver diseases such as primary biliary cholangitis and primary sclerosing cholangitis 1
- Bone-related causes: Paget's disease, bone growth, fracture healing, and certain cancers 1
- Other causes: congestive heart failure, ischemic cholangiopathy, and infiltrative liver diseases such as sarcoidosis and amyloidosis 1
Diagnostic Approach
- For mild elevations without symptoms, monitoring with repeat testing in 4-6 weeks may be appropriate 1
- For significant elevations (more than twice the upper limit of normal) or persistent elevations, additional testing such as liver ultrasound, bone scans, or specialist referral is warranted 1
- Magnetic resonance cholangiopancreaticography (MRCP) can be used to diagnose primary sclerosing cholangitis (PSC) and other biliary disorders 1
Treatment and Management
- Treatment depends entirely on the underlying cause rather than the ALP elevation itself 1
- Patients should be advised to avoid alcohol and review medications with their healthcare provider while the cause is being investigated 1
- The importance of identifying the source lies in ALP's role as an enzyme produced by multiple tissues, with elevations signaling potential damage or increased cellular activity in these tissues 1
From the Research
Causes of Elevated Alkaline Phosphatase (ALP) Levels
Elevated ALP levels can be caused by various factors, including:
- Underlying malignancy, such as infiltrative intrahepatic malignancy, bony metastasis, or both hepatic and bone metastasis 2
- Bone disease, which accounted for 29% of cases in one study 2
- Unsuspected parenchymal liver disease, which accounted for 7% of cases in one study 2
- Non-malignant infiltrative liver disease, which accounted for 2% of cases in one study 2
- Other disorders, which accounted for 5% of cases in one study 2
- Nonalcoholic fatty liver disease (NAFLD), which can present with an isolated elevated ALP instead of the more typical aminotransferase elevations 3
- Transient hyperphosphatasemia (THP) of infants and children, which is a benign condition that requires no intervention 4
- Certain types of cancer, such as liver and bone metastasis, pancreatic cancer, and lung cancer, which can cause elevated serum levels of ALP 5
- Benign familial intestinal hyperphosphatasemia (BFIH), which is a rare condition that can cause persistent elevations of ALP without underlying pathology 6
Specific Causes of Elevated ALP Levels
Some specific causes of elevated ALP levels include:
- Metastatic intrahepatic malignancy, which is a common cause of elevated ALP levels 2
- Steatohepatitis, which is a type of NAFLD that can cause elevated ALP levels 3
- Advanced liver disease, which can cause elevated ALP levels in patients with NAFLD 3
- Bone metastasis, which can cause elevated ALP levels in patients with cancer 2, 5
- Intestinal ALP, which can cause elevated ALP levels in patients with certain types of cancer or benign conditions 5, 6