What are the non-alcoholic (non-ETOH) reasons for elevated Gamma-Glutamyltransferase (GGT)?

From the Guidelines

Elevated gamma-glutamyl transferase (GGT) levels can occur due to various non-alcoholic reasons, including liver diseases, metabolic conditions, pancreatic disorders, heart failure, and endocrine disorders, as evidenced by recent studies 1.

Non-Alcoholic Causes of Elevated GGT

Some of the common non-alcoholic causes of elevated GGT include:

• Liver diseases like non-alcoholic fatty liver disease (NAFLD), viral hepatitis, and biliary obstruction, which frequently raise GGT levels 1
• Metabolic conditions including diabetes, obesity, and metabolic syndrome, associated with elevated GGT due to oxidative stress and inflammation affecting the liver 1
• Pancreatic disorders such as pancreatitis or pancreatic cancer, which can cause GGT elevation through biliary involvement
• Heart failure, leading to liver congestion and subsequent GGT increases
• Certain endocrine disorders like hyperthyroidism, which can also raise GGT levels

Diagnostic Approach

When evaluating elevated GGT, it's essential to consider these non-alcoholic causes and perform appropriate diagnostic testing, including:

• Liver function tests to assess the extent of liver damage
• Imaging studies, such as ultrasound or MRI, to visualize the liver and biliary tract
• Potentially, liver biopsy to determine the underlying cause of elevated GGT, as GGT is sensitive but not specific for liver disease 1

Clinical Implications

Elevated GGT levels can have significant clinical implications, including increased risk of liver disease, cardiovascular disease, and metabolic disorders. Therefore, it's crucial to identify the underlying cause of elevated GGT and manage it accordingly to improve patient outcomes. Recent studies suggest that addressing the underlying cause of elevated GGT can lead to improved liver function and reduced risk of associated diseases 1.

From the Research

Non-Alcoholic Reasons for Elevated GGT

• Elevated GGT levels can be associated with various conditions, including:
  • Obstructive liver disease 2
  • Use of enzyme-inducing drugs 2
  • Metabolic syndrome 3
  • Non-alcoholic fatty liver disease (NAFLD) 3
  • Cardiovascular disease, including atrial fibrillation and congestive heart failure 3
  • Obstructive sleep apnea 3
• GGT is also an independent predictor of risk for coronary heart disease, Type 2 diabetes, and stroke 2
• The enzyme has a pro-oxidant activity and a modulating influence on endothelial dysfunction, which may contribute to its association with these conditions 3

Relationship with Other Conditions

• Elevated GGT levels have been linked to increased mortality, partly due to the association between GGT and other risk factors, and partly because GGT is an independent predictor of risk 2
• The use of HMG-CoA reductase inhibitors (statins) may have pleiotropic effects, including anti-inflammatory and immunomodulatory actions, which could influence GGT levels 4, 5
• Statins may also have a protective role against diabetic complications by inhibiting the interaction between advanced glycation end-products (AGEs) and the receptor for AGEs (RAGE) 6