From the Guidelines
Elevated alkaline phosphatase (ALP) levels require a comprehensive evaluation to determine the underlying cause, which may involve additional blood tests and imaging studies to assess liver function, bone health, and other potential factors. The normal range for ALP in adults is typically between 40-130 IU/L, though this varies by laboratory 1. Elevated levels can indicate conditions affecting the liver, such as bile duct obstruction, hepatitis, or cirrhosis, as well as bone disorders like Paget's disease, bone metastases, or healing fractures 1. Other potential causes of elevated ALP include pregnancy, certain medications, or rare genetic conditions.
Key Considerations
- ALP is an enzyme produced in several tissues, primarily the liver and bones, and it helps break down proteins in the body 1.
- When cells in these tissues are damaged or highly active, more ALP is released into the bloodstream, causing elevated levels in blood tests 1.
- Measurements of gamma-glutamyl transpeptidase (GGT) can help determine whether elevated ALP is of hepatic or nonhepatic origin 1.
- Concomitantly elevated GGT can confirm that an elevated ALP originates from the liver and indicates cholestasis 1.
Diagnostic Approach
- If the liver is suspected to be the source of elevated ALP, imaging of the biliary tree may be necessary to determine the etiology of extrahepatic or intrahepatic cholestasis 1.
- Choledocholithiasis is the most common cause of extrahepatic biliary obstruction and elevated ALP of liver origin 1.
- Isolated elevated ALP of hepatic origin that persists over time suggests a chronic cholestatic process, such as partial bile duct obstruction, primary biliary cholangitis, primary sclerosing cholangitis, or drug-induced cholestasis 1.
Management
- No specific medication is universally recommended for elevated ALP, as treatment targets the underlying cause rather than the enzyme level itself 1.
- For example, if the elevation is due to a bile duct obstruction, procedures to relieve the blockage may be needed; if it's related to bone disease, specific bone-directed therapies would be appropriate 1.
From the Research
Causes of Elevated Alkaline Phosphatase
- The most common cause of elevated alkaline phosphatase (ALP) is underlying malignancy, accounting for 57% of cases, with infiltrative intrahepatic malignancy, bony metastasis, and both hepatic and bone metastasis being common causes 2.
- Bone disease is another significant cause, accounting for 29% of cases, while unsuspected parenchymal liver disease, non-malignant infiltrative liver disease, and other disorders account for the remainder 2.
- Elevated ALP levels can also be found in multiple hepatobiliary diseases and in bone diseases, and can originate in the intestine and placenta 3.
Evaluation of Elevated Alkaline Phosphatase
- The evaluation of hepatocellular injury includes testing for viral hepatitis A, B, and C, assessment for nonalcoholic fatty liver disease and alcoholic liver disease, screening for hereditary hemochromatosis, autoimmune hepatitis, Wilson's disease, and alpha-1 antitrypsin deficiency 4.
- For the evaluation of an alkaline phosphatase elevation determined to be of hepatic origin, testing for primary biliary cholangitis and primary sclerosing cholangitis should be undertaken 4.
- A liver biopsy may be considered when serologic testing and imaging fails to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible 4.
Association with Cardiovascular Disease
- Elevated levels of serum alkaline phosphatase are associated with increased risk of cardiovascular disease, coronary heart disease, and stroke, as well as their subtypes, among men and women 5.
- Higher ALP levels, even within the normal range, are significantly associated with increased risks of cardiovascular disease, in a dose-dependent manner 5.
- Regular monitoring of ALP levels may help in improving the early identification of the population at higher cardiovascular disease risk 5.