From the Guidelines
Elevated alkaline phosphatase (ALP) should be further investigated to determine its cause, with the first step being to confirm whether the elevation is isolated or accompanied by other liver enzyme abnormalities, as recommended by the most recent guidelines 1. To evaluate elevated ALP, the following steps should be taken:
- Order additional tests including gamma-glutamyl transferase (GGT) to help distinguish between liver and bone sources 1
- Conduct other liver function tests to assess the overall liver health
- Perform imaging studies like ultrasound or CT scans to visualize the liver and biliary tract
- Possibly order bone-specific ALP isoenzymes to determine if the elevation is due to bone disorders Common causes of elevated ALP include:
- Liver diseases (such as hepatitis, cirrhosis, or biliary obstruction) 1
- Bone disorders (like Paget's disease, osteomalacia, or bone metastases) 1
- Pregnancy 1
- Certain medications 1
- Some benign conditions 1 Treatment depends entirely on the underlying cause, and may include:
- Stopping hepatotoxic medications 1
- Treating underlying infections 1
- Addressing biliary obstruction 1
- Managing bone disorders 1 The significance of elevated ALP varies widely, and regular monitoring is important, especially if the cause isn't immediately apparent 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 61 patients having infiltrative intrahepatic malignancy, 52 patients having bony metastasis, and 34 patients having both hepatic and bone metastasis 2.
- Bone disease is another common cause, accounting for 29% of cases 2.
- Unsuspected parenchymal liver disease, non-malignant infiltrative liver disease, and other disorders also account for a significant proportion of cases 2.
- Defective enzyme elimination could play a major role in the pathogenesis of serum alkaline phosphatase elevations 3.
Evaluation of Elevated Alkaline Phosphatase
- Elevated ALP levels can be found in multiple hepatobiliary diseases and in bone diseases, and can also originate in the intestine and placenta 4.
- In the evaluation of elevated ALP, most patients will not require determination of its isoenzymes, but it is important to be aware of benign familial intestinal hyperphosphatasemia (BFIH) to avoid unnecessary additional studies 4.
- 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 5.
- 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 5.
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 6.
- Higher ALP levels, even within the normal range, were significantly associated with increased risks of cardiovascular disease, in a dose-dependent manner 6.
- Regular monitoring of ALP levels may help in improving the early identification of the population at higher cardiovascular disease risk 6.