From the Guidelines
Elevated alkaline phosphatase (ALP) with normal alanine aminotransferase (ALT) and aspartate aminotransferase (AST) suggests a condition affecting the biliary system rather than the liver cells themselves, and further evaluation is recommended to distinguish between liver and bone sources of elevated ALP. This pattern typically points to cholestasis, which is an obstruction of bile flow, or conditions affecting bone metabolism. The most recent and highest quality study, 1, provides guidance on the evaluation of abnormal liver function tests, including elevated ALP.
Key Considerations
- Elevated ALP can occur in a variety of conditions affecting the liver, including cirrhosis, chronic hepatitis, viral hepatitis, congestive heart failure, and ischemic cholangiopathy, as well as in bone disease such as Paget’s disease, bony metastases, or fracture.
- Measurements of gamma-glutamyl transferase (GGT) can help determine whether an elevated ALP is of hepatic or nonhepatic origin, with concomitantly elevated GGT suggesting a biliary cause.
- The degree of ALP elevation can provide clues to the underlying cause, with mild elevations often seen in infiltrative liver diseases and higher levels indicating complete biliary obstruction or bone disorders.
Recommended Evaluation
- GGT testing to distinguish between liver and bone sources of elevated ALP.
- Imaging studies such as ultrasound, CT, or MRCP to evaluate the biliary system if biliary causes are suspected.
- Bone-specific ALP isoenzyme testing if bone pathology is suspected.
- Additional workup may include testing for other liver diseases, such as viral hepatitis, autoimmune hepatitis, or primary biliary cholangitis, depending on the clinical scenario.
Treatment Approach
- Treatment depends on identifying and addressing the underlying cause rather than treating the elevated ALP itself.
- Management may involve treating the underlying liver or bone condition, or addressing any obstructive causes of cholestasis.
- The goal is to improve morbidity, mortality, and quality of life by addressing the underlying cause of the elevated ALP.
From the Research
Implications of Elevated Alkaline Phosphatase (ALP) with Normal Alanine Transaminase (ALT) and Aspartate Transaminase (AST) Levels
- Elevated ALP levels with normal ALT and AST levels can be associated with various medical conditions, including bone disease, liver disease, and certain types of cancer 2, 3, 4, 5.
- In some cases, elevated ALP levels can be caused by high bone turnover, particularly in postmenopausal women 4.
- Defective enzyme elimination can also play a role in the pathogenesis of serum ALP elevations 6.
- Isolated elevations of ALP in inpatients may normalize within months, but persistent elevations can be associated with clinically obvious diagnoses, such as terminal malignancies 3.
- The role of ALP in cancer is complex and context-dependent, with both elevated and decreased ALP activity observed in different types of cancer 5.
- ALP isoenzyme electrophoresis can help identify the source of elevated ALP levels, such as bone or liver disease 2.
- A careful history, physical exam, and routine lab studies can help detect obvious diagnoses in patients with elevated ALP levels 3.
- Further research is needed to better understand the mechanisms underlying ALP dysregulation in cancer and to identify potential therapeutic targets 5.