What are the implications of elevated Gamma-Glutamyltransferase (GGT)?

From the Guidelines

Elevated Gamma-Glutamyltransferase (GGT) levels may indicate liver damage or disease, and it is essential to consult a healthcare provider for proper evaluation and management, as the primary goal is to address the underlying cause and prevent further liver damage, thereby reducing morbidity, mortality, and improving quality of life. The implications of elevated GGT levels can be significant, and it is crucial to identify the underlying cause to provide appropriate treatment. Common causes of elevated GGT include alcohol consumption, certain medications, fatty liver disease, bile duct problems, and liver infections 1. To address elevated GGT levels, lifestyle modifications such as reducing or eliminating alcohol intake, maintaining a healthy weight through diet and exercise, managing underlying conditions like diabetes or high cholesterol, and avoiding hepatotoxic medications when possible are recommended 1. Additionally, adopting a Mediterranean-style diet rich in fruits, vegetables, whole grains, and healthy fats, regular physical activity (aim for 150 minutes weekly), and avoiding excessive acetaminophen use can help normalize GGT levels within weeks to months after addressing the underlying cause 1. Some key points to consider when evaluating elevated GGT levels include:

• The enzyme is produced in the liver and other tissues, and its elevation serves as an early indicator of liver stress before more serious damage occurs, making it an important marker for monitoring liver health.
• A mild increase in serum gamma-glutamyltransferase is the most common and early laboratory liver abnormality, present in >85% of adult Fontan patients, and may be associated with liver congestion, fibrosis, or both 1.
• Markers of cholestasis are not clearly associated with worse cardiac function, more severe liver fibrosis, or impairment of other liver function parameters, and therefore, should be interpreted with caution 1.
• The MELD-XI score has demonstrated a significant correlation with histologically proven liver fibrosis, though a specific MELD-XI cut-off value for severe liver fibrosis has not been identified, and other reports did not observe this correlation 1. It is essential to note that the management of elevated GGT levels should focus on addressing the underlying cause, rather than solely relying on medication to lower GGT levels, as there is no specific medication that directly lowers GGT, and treatment should prioritize reducing morbidity, mortality, and improving quality of life.

From the Research

Implications of Elevated Gamma-Glutamyltransferase (GGT)

Elevated GGT levels have been associated with various health implications, including:

• Increased risk of cardiovascular disease, as shown by the positive correlation between GGT levels and Framingham cardiovascular risk score 2
• Prediction of high cardiovascular risk among patients with non-alcoholic fatty liver disease, independent of traditional risk factors 2
• Increased risk of developing impaired glucose metabolism, including diabetes and impaired glucose regulation, in middle-aged and elderly individuals 3
• Association with inflammation and oxidative stress, independent of the metabolic syndrome, as indicated by elevated serum levels of C-reactive protein and lipid peroxides 4
• Prognostic value in hepatocellular carcinoma (HCC) patients, with higher GGT levels associated with poorer survival and more aggressive tumor characteristics 5

Disease Risk Association

The association between elevated GGT levels and disease risk has been consistently shown across various studies, including:

• Cardiovascular disease, with GGT being a superior marker for future disease risk compared to other known mortality risk factors 6
• Metabolic syndrome, with elevated GGT levels linked to increased risk of developing metabolic syndrome and its related disorders 6
• Liver diseases, including viral hepatitis, other infectious diseases, and life-threatening cancers, with GGT being an early predictive marker for these conditions 6

Clinical Significance

The clinical significance of elevated GGT levels lies in their potential to serve as a predictive biomarker for various diseases, allowing for early intervention and prevention. As shown by the studies, elevated GGT levels can be an indicator of:

• Increased cardiovascular risk, even in non-diabetic and non-obese individuals 2
• Development of impaired glucose metabolism, including diabetes and impaired glucose regulation 3
• Inflammation and oxidative stress, independent of the metabolic syndrome 4
• Poor prognosis in HCC patients, with higher GGT levels associated with more aggressive tumor characteristics and poorer survival 5