What are the causes of elevated Gamma-Glutamyl Transferase (GGTP) levels exceeding Alkaline Phosphatase (ALP) levels?

From the Guidelines

High GGT levels that are elevated more than alkaline phosphatase typically indicate liver disease, particularly those involving the biliary tract, with the most common causes including alcohol consumption, medications, and non-alcoholic fatty liver disease (NAFLD). The causes of high GGT more than alkaline phosphatase can be broken down into several categories, including:

• Liver diseases such as NAFLD, viral hepatitis, and bile duct obstruction
• Medications such as anticonvulsants, certain antibiotics, and statins
• Alcohol consumption, which specifically induces GGT enzyme production in the liver
• Other conditions such as pancreatic disease, heart failure with liver congestion, and certain medications like phenytoin, carbamazepine, and barbiturates that can selectively increase GGT levels 1. It's essential to note that GGT is more sensitive to liver injury and enzyme induction than alkaline phosphatase, making it a valuable marker for liver disease. If you have elevated GGT, it's crucial to discuss with your doctor about potential causes, which may require lifestyle changes like reducing alcohol intake, managing weight, or adjusting medications. Additional testing such as liver ultrasound, viral hepatitis screening, or other liver function tests may be needed to determine the specific cause 1.

Some key points to consider when evaluating high GGT levels include:

• The pattern of liver enzyme elevation, with GGT being more sensitive to liver injury and enzyme induction than alkaline phosphatase
• The presence of other symptoms or laboratory abnormalities, such as elevated aminotransferases or bilirubin
• The patient's medical history, including alcohol consumption, medication use, and underlying liver disease
• The need for additional testing, such as liver ultrasound or viral hepatitis screening, to determine the specific cause of elevated GGT levels 1.

In terms of specific causes, alcohol consumption is a common cause of elevated GGT levels, as it induces GGT enzyme production in the liver 1. NAFLD is another frequent cause, especially in people with obesity, diabetes, or metabolic syndrome 1. Other conditions, such as viral hepatitis, bile duct obstruction, and pancreatic disease, can also elevate GGT levels more than alkaline phosphatase 1.

Overall, elevated GGT levels that are higher than alkaline phosphatase require a thorough evaluation to determine the underlying cause, including a review of the patient's medical history, laboratory results, and additional testing as needed 1.

From the Research

Causes of High GGTP

• The provided studies do not directly address the causes of high GGTP (gamma-glutamyltransferase) in relation to alkaline phosphatase levels 2, 3, 4, 5, 6.
• However, it is known that GGTP is an enzyme found in many organs, including the liver, and elevated levels can indicate liver damage or disease.
• Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are two common liver diseases that can cause elevated GGTP levels, but the studies do not provide a direct comparison of GGTP and alkaline phosphatase levels in these diseases 2, 4, 5.
• The studies suggest that ALD and NAFLD have similar pathological spectra and share genetic-epigenetic factors, which may contribute to elevated GGTP levels 3, 5, 6.
• Excessive alcohol consumption and metabolic syndrome are risk factors for both ALD and NAFLD, and may also contribute to elevated GGTP levels 5, 6.

Laboratory Features

• The ratio of AST (aspartate aminotransferase) to ALT (alanine aminotransferase) is more frequently less than 1 in NAFLD than in ALD, but this does not directly relate to GGTP levels 3.
• The studies do not provide information on the relationship between GGTP and alkaline phosphatase levels in ALD and NAFLD.

Pathophysiology

• The pathophysiology of ALD and NAFLD involves cellular stress responses, including autophagy and endoplasmic reticulum (ER) stress, which may contribute to elevated GGTP levels 6.
• Gut-derived bacterial products and innate immune responses in the liver may also play a role in the pathogenesis of both ALD and NAFLD, and potentially contribute to elevated GGTP levels 6.