From the Guidelines
Alkaline phosphatase (ALP) levels should be investigated when they exceed 1.5 times the upper limit of normal (ULN) for the laboratory reference range, as recommended by the most recent guidelines 1. For most labs, this typically means ALP values above 150-180 U/L require workup, though exact thresholds vary by laboratory. When evaluating elevated ALP, first determine if the source is hepatic or non-hepatic by checking gamma-glutamyl transferase (GGT) or 5'-nucleotidase, which rise in parallel with liver-sourced ALP elevations, as noted in a study published in the Journal of the American College of Radiology 1. The workup should include:
- A thorough history focusing on medications, alcohol use, and symptoms of liver or bone disease
- Physical examination for hepatomegaly, jaundice, or bone tenderness
- Appropriate imaging such as right upper quadrant ultrasound for suspected liver pathology, as suggested by the American College of Radiology 1 Mild, isolated ALP elevations (less than 2-3 times ULN) without symptoms may be monitored, while more significant elevations warrant comprehensive evaluation, according to the guidelines published in the Journal of Hepatology 1. ALP is produced by multiple tissues including liver, bone, intestine, and placenta, so elevations can indicate various conditions including biliary obstruction, certain bone disorders, pregnancy, or normal growth in children and adolescents, as discussed in a recent study 1. It's essential to consider the patient's clinical history and medications when interpreting ALP results, as some conditions may cause elevated ALP levels, such as primary biliary cholangitis, primary sclerosing cholangitis, or drug-induced cholestasis, as noted in the study published in the Journal of the American College of Radiology 1.
From the Research
Working Up Elevated Alkaline Phosphatase (ALP)
- The level of elevation at which to start working up elevated ALP is not explicitly stated in the provided studies, but it can be inferred that any elevation of ALP should be investigated further, especially if it is disproportionate to other liver enzymes such as AST and ALT 2.
- Cholestatic injury is defined as a disproportionate elevation of ALP level compared to AST and ALT levels, and this should be evaluated for primary biliary cholangitis and primary sclerosing cholangitis 2.
- The evaluation of ALP elevation should include a history of prescribed and over-the-counter medicines, as well as testing for viral hepatitis, nonalcoholic fatty liver disease, and other liver diseases 2.
- A liver biopsy may be considered when serologic testing and imaging fail to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible 2.
- Defective elimination of ALP can also play a role in the pathogenesis of serum ALP elevations, and this should be considered in the evaluation of unexplained elevations of serum ALP 3.
- In children, an elevated ALP level is one of the markers for the diagnosis of rickets, and ALP measurements are useful in clinical and therapeutic follow-up 4.
Key Considerations
- The degree of elevation of ALP and other liver enzymes can guide the evaluation and help determine the underlying cause of the elevation 2.
- The presence of an elevated ALT has been associated with increased liver-related mortality, and this should be taken into consideration when evaluating ALP elevations 2.
- PPAR agonists have been shown to be effective in reducing ALP levels in patients with primary biliary cholangitis, and this may be a useful therapeutic option in certain cases 5.