From the Guidelines
Elevated alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels, such as ALP 121 and GGT 127, require a systematic diagnostic approach to identify the underlying cause, which may involve liver or biliary tract dysfunction, and targeted treatment to prevent progression of liver damage. The first step is to confirm the elevation with repeat testing and order additional liver function tests, including bilirubin, ALT, and AST, to assess the pattern of liver injury 1.
Diagnostic Approach
- Repeat testing to confirm elevation of ALP and GGT
- Order additional liver function tests, including bilirubin, ALT, and AST
- Ultrasound of the liver and biliary system to evaluate for biliary obstruction, gallstones, or liver masses
- Review of the patient’s clinical history and medications to identify potential causes of elevated ALP and GGT
Potential Causes and Treatment
- Biliary obstruction: intervention may be needed via ERCP or surgery
- Primary biliary cholangitis: ursodeoxycholic acid at 13-15 mg/kg/day is the standard treatment
- Autoimmune hepatitis: prednisone starting at 30-40 mg daily with gradual tapering, often combined with azathioprine 50-150 mg daily
- Medication-induced elevations: discontinuation of offending medications, such as phenytoin and certain antibiotics, if possible
- Non-alcoholic fatty liver disease: weight loss of 7-10% through diet and exercise is recommended
Importance of Identifying Underlying Cause
Identifying and treating the underlying condition is crucial for normalizing ALP and GGT levels and preventing progression of liver damage 1. Elevated ALP and GGT levels are markers of liver or biliary tract dysfunction rather than diseases themselves, and a systematic diagnostic approach followed by targeted treatment can help improve patient outcomes.
From the FDA Drug Label
Abnormalities in liver enzymes have not been associated with Ursodiol therapy and, in fact, Ursodiol has been shown to decrease liver enzyme levels in liver disease. The FDA drug label does not answer the question.
From the Research
Elevated Alkaline Phosphatase (ALP) and Gamma-Glutamyl Transferase (GGT) Levels
- ALP and GGT are liver enzymes that can be elevated in various conditions, including liver disease and bile duct obstruction 2.
- In patients with elevated ALP and GGT levels, it is essential to establish the origin of the elevation and distinguish between intrahepatic and extrahepatic cholestasis 2.
- The evaluation of albumin and prothrombin levels can help assess hepatic function and differentiate between acute and chronic diseases 2.
Diagnostic Approach
- A complete medical history, physical examination, and non-invasive diagnostic tests (e.g., serology, iron levels, autoimmunity, or abdominal ultrasound) can help diagnose liver disease in most patients 2.
- In some cases, liver biopsy may be necessary to confirm the diagnosis 2.
- Elevated GGT levels can be an indicator of drug-induced liver injury, even in patients without conventional diagnostic criteria of acute liver injury 3.
Clinical Implications
- High levels of ALP and GGT have been associated with poor prognosis in patients with metastatic pancreatic cancer, particularly those with liver metastasis 4.
- In patients with primary biliary cholangitis, normal ALP levels do not exclude the diagnosis, and GGT can be a useful biomarker in these cases 5.
- Elevated liver enzymes, including GGT, are common in Type 2 diabetes mellitus and are associated with the metabolic syndrome 6.
Next Steps
- Patients with elevated ALP and GGT levels should undergo further evaluation to determine the underlying cause of the elevation.
- This may involve additional laboratory tests, imaging studies, and/or liver biopsy.
- In some cases, discontinuation of potentially hepatotoxic medications or treatment of underlying conditions (e.g., primary biliary cholangitis) may be necessary 3, 5.