5-nucleotidase: a specialist test to find the source of a raised ALP

5-nucleotidase (5-NT or NTP) is an enzyme that removes phosphate from nucleotides. A review of laboratory liver tests describes it as a glycoprotein disseminated throughout the body's tissues and localised in cell membranes, and a review for clinicians says it is present in many organs, its clinical value lying mainly in hepatobiliary or cholestatic disease, where it is most helpful when paired with ALP and GGT.

In the liver it sits in the membranes of liver cells and bile duct cells, and when bile flow is obstructed or the ducts are inflamed it leaks into the blood, rising in step with ALP.

ALP is a routine part of liver blood tests, but it is not specific to the liver. Lab Tests Online UK explains that liver disease and blockage of bile ducts increase ALP, believed to be due to increased bile duct pressure causing the liver to make more ALP, and that bone disease, for example fracture or vitamin D deficiency, can also increase ALP. In patients with a normal bilirubin and a raised ALP, GGT can help, because it tends to rise with liver ALP but is normal in bone disease.

The clinicians' review says that when ALP is elevated, GGT and 5-nucleotidase are important tests to identify the source of the elevation. 5-nucleotidase serves the same purpose as GGT, as a second opinion on origin.

No special preparation is usually needed. A blood sample is taken from a vein in the arm and the serum is analysed. Because few laboratories run the test, samples are often sent away to a reference laboratory and results can take days or longer. Tell the clinician about all prescribed and over-the-counter medicines and supplements.

A raised 5-nucleotidase together with a raised ALP points to a liver or bile duct source. The review of liver tests says raised levels were found in obstructive jaundice, parenchymal liver disease, hepatic metastases and also bone disease in some reports, that ALP also rises along with it in intra- or extra-hepatic obstruction due to malignancy, and that levels are higher in acute hepatitis than in chronic hepatitis, attributed to shedding of cell membrane with the enzyme during cell damage or to leakage of bile containing high 5-nucleotidase activity. It reports a slight rise in the second and third trimesters of pregnancy.

The clinicians' review quotes a normal range of 0.3 to 3.2 Bodansky units, noting that levels need to be corrected with elevated serum ALP, while another review gives 0 to 15 U/L: the difference reflects the different assay methods and shows why a number from one laboratory should not be compared with another.

The test is non-specific in the sense that it is present widely in the body, rises in some other conditions, and has no single agreed reference interval. Because GGT is cheaper, widely available and is the more commonly used first choice, 5-nucleotidase is a back-up. Neither test names the cause: after the source is identified as liver or bile duct, imaging such as an ultrasound and further blood tests look for gallstones, bile duct inflammation, drug injury or tumours.

Lab Tests Online UK also notes that abnormal results in individual liver tests can occur in conditions that do not involve the liver, and that normal results can be found in patients with serious liver disease, so the set of tests is read together with symptoms.

If the ALP is explained by bone, tests of calcium, vitamin D and bone health follow. If the source is hepatobiliary, doctors arrange a liver ultrasound, review medicines and alcohol, and test for conditions such as primary biliary cholangitis. Seek urgent help for yellow skin or eyes with fever, severe upper abdominal pain, itching with dark urine and pale stools, or confusion; call 999 or attend A&E for severe symptoms.