From the Guidelines
Elevated Alkaline Phosphatase (ALP) levels are a nonspecific indicator of various conditions, including liver and bone diseases, and require further testing to determine the underlying cause, as evidenced by the most recent study in 2023 1. The significance of elevated ALP levels can be understood by considering the various sources of ALP in the body, including the liver, bones, intestines, and placenta.
- ALP is produced mainly in the liver and is present in the canalicular membrane of the hepatocyte, and its elevation can occur in a variety of conditions affecting the liver, including cirrhosis, chronic hepatitis, viral hepatitis, and congestive heart failure.
- Pathologically increased levels of ALP may also occur in bone disease, such as Paget’s disease, bony metastases, or fracture.
- Measurements of GGT can indicate whether pathologically elevated ALP is of hepatic or nonhepatic origin, as GGT is found in the liver and in the kidneys, intestine, prostate, and pancreas, but not in the bone.
- Concomitantly elevated GGT can help confirm that an elevated ALP originates from the liver and indicates cholestasis, as suggested by the study in 2023 1. Some of the key conditions associated with elevated ALP levels include:
- Cholestatic liver disease, such as primary biliary cholangitis, primary sclerosing cholangitis, intrahepatic or extrahepatic bile duct obstruction, and drug-induced cholestasis.
- Bone disease, such as Paget’s disease, bony metastases, or fracture.
- Infiltrative liver diseases, such as sarcoidosis, amyloidosis, and hepatic metastases. In clinical practice, it is essential to interpret elevated ALP levels in the context of the patient's clinical history, medications, and other laboratory tests, and to consider further testing, such as imaging of the biliary tree, to determine the underlying cause, as recommended by the study in 2023 1.
From the Research
Significance of Elevated Alkaline Phosphatase (ALP) Levels
Elevated ALP levels can be indicative of various conditions, including:
- Bone involvement from malignancy or Paget's disease 2
- Sepsis, which can cause extremely high ALP levels even with normal bilirubin 2
- Biliary obstruction, including malignant obstruction and common bile duct stones 2
- Acquired immunodeficiency syndrome (AIDS) 2, 3
- Malignant intrahepatic malignancy, which is a common cause of isolated elevated ALP 3
- Bone disease, including metastatic bone disease 3, 4
- Unsuspected parenchymal liver disease and non-malignant infiltrative liver disease 3
- Rickets, a condition caused by vitamin D nutritional deficiency, where ALP is a relevant marker for diagnosis and treatment 5
- Transient hyperphosphatasemia (THP) of infants and children, a benign condition that requires no intervention 6
Clinical Implications
Elevated ALP levels can have significant clinical implications, including:
- Increased risk of liver metastases in patients with colorectal cancer 4
- Poor prognosis in patients with elevated ALP levels 4
- Association with bone formation process and bone turnover 5
- Utility in differentiating between rickets and other disorders that can mimic rickets 5
- Importance in clinical and therapeutic follow-up of patients with rickets 5
Diagnostic Considerations
When evaluating elevated ALP levels, it is essential to consider the following:
- Age, severity, and duration of the condition may modulate ALP elevation 5
- ALP levels can be influenced by various factors, including liver function, bone metabolism, and vitamin D status 5
- A "wait and see" approach may be optimal in some cases, such as transient hyperphosphatasemia (THP) of infants and children 6
- An algorithmic approach can be useful in determining when further testing or referral is necessary 6