From the Guidelines
Elevated alkaline phosphatase (ALP) requires immediate further investigation to determine its cause, as it can indicate several underlying conditions that may impact morbidity, mortality, and quality of life. The first step should be to repeat the test to confirm the elevation and check for other liver enzymes (AST, ALT, GGT, bilirubin) and a complete blood count, as recommended by the American College of Radiology 1. If the elevation persists, determine if it's liver or bone in origin by testing for ALP isoenzymes or gamma-glutamyl transferase (GGT), considering that GGT is not found in bone and can help confirm the liver as the source of elevated ALP 1.
Some key points to consider in the investigation of elevated ALP include:
- Common liver causes include biliary obstruction, cholestasis, hepatitis, and certain medications, which may require urgent attention to prevent progression to more severe liver disease 1.
- Bone causes include Paget's disease, bone metastases, fracture healing, and vitamin D deficiency, which may also require prompt management to prevent complications 1.
- Additional testing may include abdominal ultrasound or CT scan for liver/biliary issues, or bone scans for bone pathology, guided by the clinical presentation and initial laboratory findings 1.
- Management depends on the underlying cause, and may involve specific treatments such as ursodeoxycholic acid for primary biliary cholangitis, antibiotics for cholangitis, or bisphosphonates for Paget's disease, with the goal of improving quality of life and reducing morbidity and mortality 1.
It is essential to approach elevated ALP with a thorough investigation to identify the underlying cause, given the potential implications for patient outcomes, as highlighted by the European Association for the Study of the Liver (EASL) clinical practice guidelines for the management of cholestatic liver diseases 1.
From the Research
Causes of Elevated Alkaline Phosphatase
- Elevated alkaline phosphatase (ALP) can be caused by various factors, including liver disease, bone disease, and other conditions 2, 3, 4.
- A study found that the most common cause of ALP elevation was underlying malignancy, accounting for 57% of cases, followed by bone disease (29%), and unsuspected parenchymal liver disease (7%) 3.
- Another study suggested that elevated ALP in children can be benign and require no intervention, known as transient hyperphosphatasemia (THP) of infants and children 5.
Diagnostic Approach
- The diagnostic workup of a patient with elevated ALP levels can be costly and may involve various tests, including liver function tests and imaging studies 2, 5.
- A study proposed an algorithm to determine when a "wait and see" approach is optimal for children with elevated ALP levels, avoiding further tests or referrals 5.
- The value of serum ALP, bilirubin, and other laboratory tests in distinguishing between benign and malignant diseases causing jaundice and cholestasis has been evaluated, with serum bilirubin and ALP being the most potential tests 6.
Clinical Significance
- Elevated ALP levels can be associated with significant clinical conditions, including metastatic intrahepatic malignancy, and should not be ignored 3.
- A study found that 47% of patients with isolated, elevated ALP levels died within an average of 58 months after identification, highlighting the importance of prompt evaluation and diagnosis 3.
- Persistent elevations of ALP without underlying pathology have been reported, and it is essential to be aware of this entity to avoid unnecessary additional studies 4.