Cholestatic liver disease is associated with elevated alkaline phosphatase with or without elevations in bilirubin. These elevations indicate damage to the bile ducts. Alk Phos elevations are not specific for liver disease and additional tests may be needed to assess the source of the problem. GGT and or 5' Nucleotidase combined with an elevated alkaline phosphatase helps to differentiate between hepatobiliary origin vs bone origin. (If the GGT or 5 prime Nucleotidase are normal, then the origin is NOT for the liver).

Alkaline Phosphatase

Alkaline phosphatase is an enzyme of uncertain physiological function. In the liver, cholestasis leads to a de novo increase in the production of this enzyme by the bile duct epithelium and the canalicular membrane of the hepatocytes. Consequently, alkaline phosphatase levels may be normal in acute biliary obstruction and the elevation of the enzyme may not be seen until after a few days. Non-hepatic sources of alkaline phosphatase are bones, intestine and placenta.

Gamma-Glutamyltranspeptidase (GGT)

GGT is also found in hepatocytes and bile duct epithelial cells. It is a very sensitive test of hepatobiliary disease (both hepatocellular and cholestatic injuries). However, its specificity is poor as GGT elevation can be seen in a wide range of non-hepatic diseases, including alcoholism, pancreatic disease, chronic obstructive pulmonary disease and renal failure. Because GGT is not elevated in bone disease, it is mainly used to confirm the liver as the source of increased alkaline phosphatase.

5'-Nucleotidase (5'N)

Although 5'N has a wide body distribution, its elevation is generally associated with hepatobiliary pathology. Like GGT, 5'N is not elevated in bone disease and it is therefore useful in confirming hepatic origin of alkaline phosphatase. Of note, the increase in 5'N may not parallel the increase in alkaline phosphatase.

Bilirubin

Bilirubin can be elevated during cholestatic and hepatic injury and is described in greater detail in the next section.