From the Guidelines
Elevated alkaline phosphatase (ALP) levels should be evaluated by determining the source of elevation through a comprehensive approach, including fractionation of ALP and additional liver function tests, to guide treatment directed at the underlying cause. The evaluation process begins with assessing the patient's clinical history and medications, as elevated ALP can occur in various conditions affecting the liver, such as cirrhosis, chronic hepatitis, and cholestatic liver disease, as well as in bone disease like Paget’s disease or bony metastases 1. To differentiate between hepatic and nonhepatic origins of elevated ALP, measurements of gamma-glutamyl transpeptidase (GGT) can be helpful, as concomitantly elevated GGT suggests that the elevated ALP originates from the liver and indicates cholestasis 1. Key steps in the evaluation include:
- Ordering fractionation of ALP to distinguish between bone, liver, intestinal, or placental origins
- Performing additional liver function tests including AST, ALT, GGT, bilirubin, and albumin to assess for hepatobiliary disease
- Considering ultrasound of the liver and biliary system if liver origin is suspected, potentially followed by more advanced imaging
- Obtaining calcium, phosphorus, PTH, and vitamin D levels, along with bone imaging for bone-origin ALP Treatment is then directed at the underlying cause, with options including:
- Ursodeoxycholic acid for cholestatic conditions
- Endoscopic or surgical intervention for biliary obstruction
- Immunosuppressants for autoimmune hepatitis
- Vitamin D supplementation for bone-related elevations due to deficiency
- Bisphosphonates for Paget's disease Regular monitoring of ALP levels every 3-6 months is crucial to assess treatment response, as ALP elevation reflects increased enzyme production by affected tissues, with different isoenzymes originating from different organs 1.
From the Research
Evaluation Steps for Elevated Alkaline Phosphatase (ALP) Levels
- The first step in evaluating elevated ALP levels is to determine the origin of the elevation, with the evaluation of gamma-glutamyl transferase (GGT) levels to confirm the hepatic origin 2.
- A secondary outcome is to distinguish the presence of an extrahepatic (biliary obstruction) or intrahepatic (primary biliary cirrhosis, primary sclerosing cholangitis, drugs, etc.) cholestasis, in these cases, the most important test should be the abdominal ultrasound, in order to evaluate the biliary system 2.
- The evaluation of albumin and prothrombin levels evaluates the hepatic function per se, allowing to differentiate between acute and chronic diseases 2.
Treatment Steps for Elevated Alkaline Phosphatase (ALP) Levels
- The treatment of elevated ALP levels depends on the underlying cause, and it is essential to identify and treat the underlying disease 3, 4.
- In cases of underlying malignancy, treatment should be focused on the malignancy itself, and in cases of bone disease, treatment should be focused on the bone disease 3.
- In cases of unsuspected parenchymal liver disease, non-malignant infiltrative liver disease, or other disorders, treatment should be focused on the specific disease 3.
Diagnostic Approach
- A complete medical history, an appropriate physical examination, and the appropriate application of non-invasive diagnostic tests (serology, iron levels, autoimmunity, or abdominal ultrasound) allow to perform a right diagnosis in most patients, making more complex tests, including liver biopsy, secondary 2.
- An algorithm can be utilized as a guide in a primary care setting to arrive at the diagnosis of transient hyperphosphatasemia (THP) and avoid further tests or referrals 5.
- The ratio of the transaminases in serum (AST/ALT) and the mitochondrial isoenzyme of AST are frequently higher in alcoholic than in non-alcoholic liver diseases, and can be used to discriminate between hepatic and extrahepatic causes of ALP elevation 6.