From the Guidelines
Elevated Alkaline Phosphatase (ALP) levels are a significant indicator of potential liver disease or bone disorders, and their implications should be thoroughly investigated through additional tests, including gamma-glutamyl transferase (GGT), to determine the underlying cause and guide appropriate treatment. The enzyme ALP is primarily found in the liver, bones, intestines, and placenta, with normal levels ranging from 20-140 IU/L in adults, though reference ranges may vary between laboratories 1. Elevated ALP levels can indicate liver disease, such as biliary obstruction, hepatitis, or cirrhosis, or bone disorders like Paget's disease, osteomalacia, or bone metastases.
Key Considerations
- ALP is produced mainly in the liver and is present in the canalicular membrane of the hepatocyte, and its elevation can occur in various conditions affecting the liver, including cirrhosis, chronic hepatitis, viral hepatitis, and congestive heart failure 1.
- Pathologically increased levels of ALP may occur in cholestatic liver disease, such as primary biliary cholangitis, primary sclerosing cholangitis, intrahepatic or extrahepatic bile duct obstruction, and drug-induced cholestasis 1.
- Measurements of GGT can help differentiate between liver and bone sources of elevated ALP, as GGT is elevated only in liver disease 1.
- Complete evaluation may include liver function tests, imaging studies like ultrasound or CT scans, and occasionally bone-specific ALP isoenzyme testing to determine the etiology of elevated ALP levels 1.
Diagnostic Approach
- In patients presenting with elevated serum markers of cholestasis, a diagnosis of large duct primary sclerosing cholangitis (PSC) should be made in the presence of typical findings on high-quality cholangiography and after exclusion of secondary causes 1.
- Magnetic resonance cholangiopancreaticography (MRCP) is the preferred diagnostic test for PSC, with a pooled sensitivity and specificity of 86% and 94%, respectively 1.
- A diagnosis of small duct PSC should be considered in patients with elevated serum markers of cholestasis of unknown cause, normal high-quality cholangiography, and compatible histology of PSC, particularly in those with concomitant inflammatory bowel disease (IBD) 1.
Treatment and Management
- Treatment targets the underlying cause of elevated ALP levels rather than the ALP level itself, and may involve management of liver disease, bone disorders, or other conditions affecting bile flow or bone metabolism 1.
- ALP elevations are significant because they help identify conditions affecting bile flow or bone metabolism, serving as an important diagnostic marker in clinical medicine 1.
From the Research
Implications of Elevated Alkaline Phosphatase (ALP) Levels
Elevated ALP levels can have various implications, including:
- Underlying malignancy, with studies showing that it is the most common cause of ALP elevation 2
- Bone disease, which accounts for a significant proportion of cases with elevated ALP levels 2, 3
- Unsuspected parenchymal liver disease, non-malignant infiltrative liver disease, and other disorders 2
- Benign transient hyperphosphatasemia, a rare condition characterized by isolated highly elevated ALP activity in the absence of liver or bone disease 3, 4
- Sepsis, which can cause extremely high elevations of ALP, even with normal bilirubin levels 5
- Biliary obstruction, AIDS, and diffuse liver metastases, which are also associated with elevated ALP levels 5
Clinical Significance
The clinical significance of elevated ALP levels should not be underestimated, as it can be associated with serious underlying conditions. Providers should be aware of the potential implications of an elevated ALP level and investigate further to determine the cause 2. In some cases, elevated ALP levels can be benign and transient, but it is essential to rule out other possibilities before establishing a diagnosis 3, 4.
Diagnostic Approach
When evaluating elevated ALP levels, it is crucial to consider the patient's medical history, clinical presentation, and laboratory results. Determining the isoenzymes of ALP may not be necessary in most cases, but it can be helpful in certain situations 6. A thorough diagnostic approach can help identify the underlying cause of elevated ALP levels and guide appropriate management.