What does Gamma-Glutamyl Transferase (GGT) show?

What Gamma-Glutamyl Transferase (GGT) Shows

Gamma-glutamyl transferase (GGT) is primarily a marker of hepatobiliary disease and alcohol consumption, serving as one of the most sensitive indicators of liver injury, though it has poor specificity for particular etiologies. 1, 2

Primary Clinical Significance of GGT

• GGT is an enzyme found in cell membranes of several body tissues, including liver, kidneys, intestine, prostate, and pancreas, but not in bone 1, 2
• GGT plays a key role in glutathione metabolism and cellular antioxidant defense mechanisms 3, 4
• GGT is the most sensitive laboratory marker for detecting chronic alcohol consumption, with a sensitivity of 73% for detecting daily ethanol consumption >50g 1
• GGT helps determine whether elevated alkaline phosphatase (ALP) originates from the liver or other tissues (e.g., bone) 1, 2
• GGT increases occur earlier and persist longer than ALP elevations in cholestatic disorders 2

Common Causes of Elevated GGT

Alcohol-Related

• Alcohol consumption is the most common cause of elevated GGT, occurring in approximately 75% of habitual drinkers 2, 5
• Daily alcohol consumption exceeding 60g can lead to elevated GGT 2
• GGT levels typically recover slowly following abstinence from alcohol 2, 5

Liver and Biliary Disease

• Cholestatic liver diseases, including primary biliary cholangitis and primary sclerosing cholangitis 2
• Intrahepatic or extrahepatic bile duct obstruction 2
• Viral hepatitis, cirrhosis, and other chronic liver diseases 2
• Biliary strictures and infections 2
• Nonalcoholic fatty liver disease (NAFLD) 2

Medication-Related

• Common medications that can elevate GGT include interferon, antipsychotics, beta-blockers, bile acid resins, estrogens, protease inhibitors, retinoic acid drugs, sirolimus, steroids, tamoxifen, and thiazides 2

Metabolic Conditions

• Diabetes and insulin resistance 2
• Obesity 2
• Metabolic syndrome 6, 7

Diagnostic Interpretation

• GGT elevation alone has low specificity and should be interpreted in context with other liver enzymes 2
• When combined with elevated ALP, GGT confirms the hepatobiliary origin of ALP elevation 1, 2
• An AST/ALT ratio exceeding 2 (or 3) with elevated GGT suggests alcoholic hepatitis 2
• GGT elevation combined with elevated mean corpuscular volume (MCV) increases sensitivity for detecting alcohol consumption 2
• In pediatric patients, GGT reference ranges are age-dependent, with levels at birth approximately 6-7 times the adult upper limit, declining to adult levels by 5-7 months of age 8

Emerging Roles of GGT as a Biomarker

• GGT is increasingly recognized as a predictor of cardiovascular disease risk 6, 7
• Elevated GGT is associated with increased risk of metabolic syndrome, diabetes, and all-cause mortality 6, 4
• GGT may serve as a biomarker for oxidative stress 4, 7
• High GGT levels in patients with chronic liver diseases independently predict clinical outcomes 2

Clinical Approach to Elevated GGT

• Identify and address the underlying cause (alcohol cessation, medication adjustment, treatment of underlying disease) 2
• For alcohol-related elevations, complete abstinence is recommended as GGT levels recover slowly following cessation 2, 5
• In suspected cholestatic drug-induced liver injury, blood tests should be repeated within 7-10 days 2
• For suspected hepatocellular drug-induced liver injury, testing should be repeated within 2-5 days 2
• Patients with advanced liver disease should undergo liver-specific physical examination and comprehensive liver function tests at least every 6 months 2

Important Caveats

• GGT loses specificity for alcohol in advanced liver disease because its activity is elevated in patients with extensive fibrosis regardless of cause 1
• Serum GGT activity is influenced not only by alcohol consumption but also by body mass index (BMI) and sex 1
• Some specific liver diseases, such as progressive familial intrahepatic cholestasis (PFIC) types 1 and 2, present with normal or low GGT despite significant cholestasis 1, 8
• There has been a general upward trend in population levels of GGT over time, particularly in the US and Korea, coinciding with rising rates of metabolic syndrome 6