What causes elevated bilirubin and Gamma-Glutamyl Transferase (GGT) levels?

From the Guidelines

Elevated bilirubin and Gamma-Glutamyl Transferase (GGT) levels are typically caused by liver disease, biliary obstruction, or certain medications, with liver diseases like hepatitis, alcoholic liver disease, and non-alcoholic fatty liver disease being common causes, as noted in the most recent study 1. The liver plays a crucial role in processing bilirubin from broken-down red blood cells, and GGT is an enzyme found in liver and biliary tissue that increases with cellular damage, explaining why these markers rise together in many liver and biliary conditions. Some key points to consider include:

• Liver diseases such as hepatitis, alcoholic liver disease, and non-alcoholic fatty liver disease commonly raise both bilirubin and GGT levels 1.
• Biliary obstruction from gallstones, tumors, or strictures can block bile flow, increasing these levels 1.
• Medications including certain antibiotics, anticonvulsants, and statins can cause elevations in bilirubin and GGT 1.
• Alcohol consumption significantly impacts GGT levels, making it a sensitive marker for alcohol use 1.
• Hemolytic conditions like sickle cell disease can specifically raise bilirubin by increasing red blood cell breakdown 1.
• Genetic conditions such as Gilbert's syndrome cause mild bilirubin elevation without affecting GGT 1. When these markers are elevated, reducing alcohol intake, stopping hepatotoxic medications, and treating underlying conditions are essential steps, as recommended by the most recent guidelines 1. It is also important to note that the measurement of GGT can indicate whether an elevated alkaline phosphatase (ALP) is of hepatic or non-hepatic origin, and concomitantly elevated GGT can help confirm that an elevated ALP originates from the liver and indicates cholestasis 1.

From the Research

Causes of Elevated Bilirubin and Gamma-Glutamyl Transferase (GGT) Levels

• Elevated bilirubin and GGT levels can be caused by various liver diseases, including metabolic syndrome 2, Fontan-associated liver disease 3, and severe COVID-19 infection 4.
• In patients with metabolic syndrome, elevated GGT activity is associated with lower bilirubin levels, which may contribute to systemic oxidative stress 2.
• In Fontan-associated liver disease, elevated GGT levels are associated with lower albumin levels and higher levels of alanine transaminase (ALT) 3.
• Severe COVID-19 infection can cause liver injury, leading to elevated levels of ALT, AST, GGT, and bilirubin 4.
• Other causes of elevated bilirubin levels include Gilbert's syndrome, a benign condition characterized by mildly elevated unconjugated bilirubin 5.
• GGT levels can also be elevated in various liver diseases, including primary biliary cholangitis, drug-induced liver injury, alcoholic liver disease, and non-alcoholic fatty liver disease 6.

Relationship Between Bilirubin and GGT Levels

• In patients with metabolic syndrome, there is an inverse relationship between bilirubin and GGT levels, with lower bilirubin levels associated with higher GGT activity 2.
• In Fontan-associated liver disease, elevated GGT levels are associated with lower total bilirubin levels 3.
• In severe COVID-19 infection, elevated GGT and bilirubin levels are common in more severe patients 4.
• In Gilbert's syndrome, mildly elevated unconjugated bilirubin is associated with reduced prevalence of chronic diseases, including cardiovascular diseases and type 2 diabetes mellitus 5.

Clinical Significance of Elevated Bilirubin and GGT Levels

• Elevated bilirubin and GGT levels can indicate liver disease or dysfunction, and may be associated with increased risk of chronic diseases, such as cardiovascular disease and type 2 diabetes mellitus 2, 5.
• In patients with Fontan-associated liver disease, elevated GGT levels are associated with lower albumin levels and higher levels of ALT, and may indicate progression of fibrosis 3.
• In severe COVID-19 infection, elevated GGT and bilirubin levels may indicate liver injury and increased risk of mortality 4.
• GGT levels can have different characteristics in different liver diseases, and may be associated with cholestasis, oxidative stress, or other pathogenic mechanisms 6.