What is the significance of elevated Gamma-Glutamyl Transferase (GGT) and liver enzymes?

From the Guidelines

Elevated GGT and liver enzymes are a significant concern and require immediate attention to prevent further liver damage and disease. The most recent and highest quality study, 1, suggests that liver-related enzymes, bilirubin, or gamma-glutamyl transferase (GGT) may indicate alcohol use, but are not specific for alcohol use. To address elevated GGT and liver enzymes, consider the following steps:

• Reduce or eliminate alcohol consumption immediately, as alcohol is a common cause of elevated liver enzymes.
• Adopt a healthy diet low in saturated fats and high in fruits, vegetables, and whole grains.
• Exercise regularly, aiming for at least 150 minutes of moderate-intensity activity per week.
• Lose weight if overweight or obese, as excess weight can contribute to fatty liver disease.
• Schedule a follow-up blood test in 4-6 weeks to monitor enzyme levels.
• Consider additional testing such as an ultrasound or CT scan of the liver to check for structural abnormalities.
• If levels remain elevated, your doctor may recommend medications like ursodeoxycholic acid (300-600 mg daily) or vitamin E (800 IU daily) to help reduce inflammation and improve liver function, as suggested by 1. It is essential to note that GGT is particularly sensitive to alcohol use and certain medications, and other elevated enzymes like ALT and AST may suggest inflammation or damage to liver cells, as mentioned in 1. By addressing potential causes and adopting a healthier lifestyle, you can often improve liver function and prevent further damage. However, persistent elevation may require more extensive medical evaluation to identify and treat underlying conditions, as recommended by 1 and 1.

From the FDA Drug Label

Cases of hepatitis and clinically significant liver dysfunction were observed in association with naltrexone hydrochloride exposure during the clinical development program and in the postmarketing period. Transient, asymptomatic hepatic transaminase elevations were also observed in the clinical trials and postmarketing period When patients presented with elevated transaminases, there were often other potential causative or contributory etiologies identified, including pre-existing alcoholic liver disease, hepatitis B and/or C infection, and concomitant usage of other potentially hepatotoxic drugs Although clinically significant liver dysfunction is not typically recognized as a manifestation of opioid withdrawal, opioid withdrawal that is precipitated abruptly may lead to systemic sequelae, including acute liver injury.

The significance of elevated Gamma-Glutamyl Transferase (GGT) and liver enzymes in patients taking naltrexone is that it may indicate hepatotoxicity or liver dysfunction.

• Elevated liver enzymes may be a sign of liver injury or disease.
• GGT is a liver enzyme that can be elevated in cases of liver damage or disease.
• Patients taking naltrexone should be monitored for signs of liver dysfunction and hepatotoxicity.
• If elevated liver enzymes or GGT are observed, the patient should be evaluated for other potential causes, such as pre-existing liver disease or concomitant use of hepatotoxic drugs 2.
• The use of naltrexone hydrochloride should be discontinued in the event of symptoms and/or signs of acute hepatitis 2.

From the Research

Significance of Elevated Gamma-Glutamyl Transferase (GGT) and Liver Enzymes

Elevated GGT and liver enzymes can be indicative of various underlying conditions, including liver disease, metabolic dysfunction, and alcohol intake.

• The most common causes of elevated liver enzymes include non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease, and hepatitis C virus infection 3.
• Elevated GGT levels are often associated with NAFLD, alcohol intake, and hepatotoxicity 3.
• A study found that individuals with frequently elevated GGT levels are at a higher risk of developing fatty liver disease, with high triglyceride levels being an independent predictor of fatty liver changes in these individuals 4.

Evaluation and Diagnosis

The evaluation of elevated liver enzymes should be deliberate and focused, taking into account pre-test probabilities and prior evaluations performed 5.

• A retrospective cohort study found that consecutive elevated GGT levels increase the risk for fatty liver, and high triglyceride levels in those individuals further independently increase the risk 4.
• In patients treated with immune checkpoint inhibitors, liver enzyme elevation is common, but often has a cause other than immunotoxicity, and a biochemical signature with higher ALT and ALT/AST ratio may help identify patients at a higher likelihood of immunotoxicity 6.
• Initial laboratory testing for mildly elevated transaminase levels should assess complete blood cell count, blood glucose, lipid profile, and other relevant markers, and patients should be counseled about moderation or cessation of alcohol use, weight loss, and avoidance of hepatotoxic drugs 7.

Associated Conditions and Risk Factors

Elevated GGT and liver enzymes have been associated with various conditions, including:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcoholic liver disease as common causes of mildly elevated transaminase levels 7.
• Drug-induced liver injury, chronic hepatitis B and C, and hereditary hemochromatosis as uncommon causes of elevated transaminase levels 7.
• Alpha1-antitrypsin deficiency, autoimmune hepatitis, and Wilson disease as rare causes of elevated transaminase levels 7.
• Celiac disease, hyperthyroidism, rhabdomyolysis, and pregnancy-associated liver disease as extrahepatic causes of elevated transaminase levels 7.