From the Guidelines
Elevated alkaline phosphatase (ALP) levels should be investigated further to determine the underlying cause, with a focus on differentiating between hepatic and non-hepatic origins, as suggested by the most recent guidelines 1. The first step in evaluating elevated ALP levels is to repeat the blood test to confirm the elevation and check for other liver function tests, such as gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin, as well as calcium levels. Some key points to consider in the diagnostic workup include:
- Concomitantly elevated GGT can help confirm that an elevated ALP originates from the liver and indicates cholestasis 1.
- 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. Treatment depends entirely on the underlying cause rather than the elevated ALP itself, and may involve discontinuing certain medications, surgical intervention, or specific treatments for bone or liver diseases. While awaiting diagnosis, no specific dietary restrictions are typically needed, but avoiding alcohol is advisable to prevent additional liver stress. It is essential to note that ALP is also found in bone and can be elevated in conditions such as Paget's disease, bony metastases, or fracture, highlighting the need for a comprehensive diagnostic approach 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 contribute to elevated ALP levels 2.
Pathophysiology of Alkaline Phosphatase
- Serum alkaline phosphatase activity is a routine clinical measurement, but physicians' knowledge of its pathophysiology is limited to the concept that an elevated serum alkaline phosphatase suggests disease of liver or bone 3.
- Defective enzyme elimination could play a major role in the pathogenesis of serum alkaline phosphatase elevations 3.
Evaluation of Abnormal Liver Chemistries
- Cholestatic injury is defined as disproportionate elevation of alkaline phosphatase level as compared with AST and ALT levels 4.
- The evaluation of an alkaline phosphatase elevation determined to be of hepatic origin includes testing for primary biliary cholangitis and primary sclerosing cholangitis 4.
Association with Cardiovascular Disease
- Elevated levels of serum alkaline phosphatase are associated with increased risk of cardiovascular disease, coronary heart disease, and stroke 5.
- Higher ALP levels, even within the normal range, are significantly associated with increased risks of cardiovascular disease, in a dose-dependent manner 5.