What are the causes of elevated Alkaline Phosphatase (ALP) and Gamma-Glutamyl Transferase (GGT)?

From the Guidelines

Elevated alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels can be caused by various conditions affecting the liver, biliary tract, and other organs, with the most common causes including cholestasis, hepatocellular damage, and infiltrative liver diseases, as noted in the study by 1. The causes of raised ALP and GGT can be categorized into several groups, including:

• Cholestatic liver disease, such as primary biliary cholangitis, primary sclerosing cholangitis, and drug-induced cholestasis, which can cause elevated ALP with or without elevated bilirubin, as discussed in the study by 1
• Hepatocellular damage from viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, and autoimmune hepatitis, which can also raise these enzymes, as mentioned in the study by 1
• Infiltrative liver diseases, such as cancer metastases, lymphoma, and amyloidosis, which frequently elevate both markers, as noted in the study by 1
• Bone disorders, which primarily affect ALP (not GGT) due to increased osteoblastic activity in conditions like Paget's disease, osteomalacia, and bone metastases, as discussed in the study by 1
• Medications, including phenytoin, carbamazepine, phenobarbital, and oral contraceptives, which can increase these enzymes, as mentioned in the study by 1
• Other causes, such as pancreatitis, renal failure, congestive heart failure, and hyperthyroidism, which can also elevate ALP and GGT levels, as noted in the study by 1 It is essential to note that GGT can be elevated by alcohol consumption, even without liver damage, and that the concomitant elevation of ALP and GGT typically suggests hepatobiliary disease rather than isolated bone pathology, as GGT helps distinguish between hepatic and non-hepatic sources of ALP elevation, as discussed in the study by 1.

From the Research

Causes of Raised ALP and GGT

The causes of raised Alkaline Phosphatase (ALP) and Gamma-Glutamyl Transferase (GGT) can be attributed to various factors, including:

• Hepatobiliary disease, as indicated by elevated serum levels of these enzymes 2
• Cholestasis, which can lead to increased activities of AP and G-GT 2
• Alcoholic liver disease, viral hepatitis, and drug-induced liver disease, which are common diagnoses in patients with elevated transaminases 2
• Primary biliary cholangitis (PBC), where GGT is a serum marker of cholestasis and a prognostic marker for liver transplantation or death 3
• Metastatic pancreatic cancer, where high levels of ALP and GGT are related to poor prognosis 4
• Chronic kidney disease (CKD), where high levels of GGT and ALP are independent predictors of mortality 5
• Hepatitis G virus (HGV) infection, which can cause elevated gamma-GT and alkaline phosphatase levels 6

Specific Conditions Associated with Raised ALP and GGT

Some specific conditions that can lead to raised ALP and GGT include:

• Liver metastasis, where high levels of ALP and GGT are associated with poor prognosis 4
• Non-alcoholic steatosis, which can cause elevated transaminases 2
• Genetically determined liver disease, autoimmune liver disease, and drug-induced liver disease, which can also lead to elevated liver enzymes 2
• Bile duct lesions, which can be associated with HGV infection and elevated cholestatic enzymes 6

Biochemical Associations

Raised ALP and GGT can be associated with other biochemical abnormalities, such as:

• Elevated uric acid, triglycerides, alanine aminotransferase, ferritin, and C-reactive protein levels in patients with CKD 5
• Elevated serum concentration of transaminases, such as AST and ALT, in patients with hepatobiliary disease 2