What are the next steps in managing a patient with mildly elevated Alkaline Phosphatase (ALP) levels but normal Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) levels?

From the Guidelines

The next steps in managing a patient with mildly elevated alkaline phosphatase (ALP) but normal AST and ALT levels should focus on identifying the source of the elevation, starting with determining if the ALP elevation is of hepatic or non-hepatic origin by ordering gamma-glutamyl transferase (GGT) or 5'-nucleotidase tests, as suggested by the American College of Radiology in their 2023 guidelines 1. To approach this patient, consider the following steps:

• Determine the source of ALP elevation by ordering GGT or 5'-nucleotidase tests to differentiate between hepatic and non-hepatic causes.
• Conduct a comprehensive history and physical examination to identify risk factors for liver disease, review medications for potential hepatotoxicity, and assess for symptoms suggestive of cholestatic disease.
• Use imaging studies such as ultrasound of the liver and biliary tract to evaluate for obstruction, masses, or fatty liver disease, as these conditions can cause elevated ALP levels.
• Consider testing for primary biliary cholangitis with anti-mitochondrial antibodies if the clinical presentation and initial workup suggest this diagnosis.
• If bone pathology is suspected, bone-specific ALP isoenzyme testing may be warranted to determine if the elevation is due to a bone-related condition rather than a liver issue.
• For mild isolated ALP elevations (less than 2-3 times the upper limit of normal) without symptoms, monitoring with repeat testing in 2-3 months may be appropriate before pursuing an extensive workup, as ALP can be elevated due to non-pathological conditions such as pregnancy, adolescent growth, or recent food consumption, as noted in the 2023 guidelines from the Journal of the American College of Radiology 1.

From the Research

Managing a Patient with Mildly Elevated Alkaline Phosphatase (ALP) Levels

• The patient's ALP level is mildly elevated at 124 IU/L, with normal Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) levels 2.
• According to a study published in the Journal of Clinical Gastroenterology, isolated elevations of ALP in inpatients may be associated with a variety of medical illnesses and often normalize within months 2.
• If the ALP elevation is persistent, there is usually a clinically obvious diagnosis, and a reasonable approach to such patients is a careful history, physical exam, and routine lab studies to detect obvious diagnoses, followed by repeat enzyme determination at 1-3 months 2.

Possible Causes of Elevated ALP Levels

• Elevated ALP levels can be caused by a variety of conditions, including bone involvement from malignancy or Paget's disease, sepsis, biliary obstruction, and AIDS 3.
• A study published in the Mayo Clinic Proceedings found that cholestatic liver disease is characterized by an increase in the ALP level that is 3 to 5 times greater than the upper limit of normal, with only a mild increase of transaminases 4.
• In some cases, elevated ALP levels can be caused by non-hepatic conditions, such as left atrial myxoma 5.

Next Steps in Management

• Given the patient's mildly elevated ALP level and normal AST and ALT levels, a careful history, physical exam, and routine lab studies should be performed to detect obvious diagnoses 2.
• Repeat enzyme determination at 1-3 months may be necessary to monitor the patient's ALP level and determine if it normalizes or persists 2.
• If the ALP elevation persists, further evaluation, including imaging studies and specialized serum tests, may be necessary to determine the underlying cause of the elevation 4.