From the Guidelines
Elevated levels of both alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) strongly suggest liver or biliary tract disease, with GGT helping to confirm that an elevated ALP is of hepatic rather than bone origin. When evaluating liver disease, these enzymes are often measured together as they provide complementary information. ALP is primarily found in the liver, bone, intestines, and placenta, while GGT is mainly present in the liver and biliary tract. Elevated ALP levels can indicate cholestatic liver diseases, bone disorders, or pregnancy, while GGT is more specific to the hepatobiliary system and is particularly sensitive to alcohol consumption and medication effects 1. The relationship between these enzymes is most valuable diagnostically when interpreted together:
- If both ALP and GGT are elevated, this strongly suggests liver or biliary tract disease rather than bone pathology.
- GGT can help confirm that an elevated ALP is of hepatic rather than bone origin.
- GGT may rise earlier than ALP in some liver conditions, making it a more sensitive but less specific indicator of liver dysfunction. In clinical practice, these enzymes are typically measured as part of a comprehensive liver function panel to help diagnose and monitor liver diseases, as seen in guidelines for diagnosing conditions like primary sclerosing cholangitis 1.
From the Research
Relationship Between Alkaline Phosphatase and GGT
- Alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) are both enzymes used as indicators of hepatobiliary disease 2.
- Elevated serum levels of ALP and GGT are often seen in cholestasis, but these enzymes are not liver-specific and can be elevated in other conditions as well 2, 3.
- GGT is a marker of oxidative stress and cholestasis, and its levels can be elevated in various liver diseases, including primary biliary cholangitis, drug-induced liver injury, alcoholic liver disease, and non-alcoholic fatty liver disease 4.
- The relationship between ALP and GGT can vary depending on the underlying liver disease, with positive correlations observed in some cases, such as primary biliary cholangitis and alcoholic liver disease 4.
- GGT activity has limited utility in assessing ALP elevations, with a sensitivity of 46.6% and specificity of 85.0% for predicting hepatic ALP elevation 5.
- Elevated levels of GGT and ALP have been associated with an increased risk of cardiovascular disease mortality, with a direct nonlinear relationship observed between GGT and ALP levels and the risk of cardiovascular disease mortality 6.
Clinical Significance
- The ratio of transaminases (AST/ALT) and the mitochondrial isoenzyme of AST can help differentiate between alcoholic and non-alcoholic liver diseases 2.
- A hepatic enzyme pattern (predominant transaminase elevation) should be discriminated from a cholestatic pattern (predominant ALP and GGT elevation) to guide further diagnosis and treatment 2.
- GGT levels can be used to monitor oxidative stress and cholestasis in various liver diseases, but its diagnostic value is limited due to its low specificity 4.
- ALP and GGT levels should be interpreted in the context of other clinical and laboratory findings to guide diagnosis and treatment of liver diseases 3, 5.