Activated complement factor 3 is associated with liver fat and liver enzymes: the CODAM study

Area of Science:

• Immunology
• Hepatology
• Biochemistry

Background:

• The complement system's role in alcoholic and nonalcoholic liver disease is understudied in humans.
• Investigating complement activation marker C3a in relation to liver fat and damage is crucial.

Purpose of the Study:

• To determine if circulating levels of activated complement factor 3 (C3a) are associated with hepatic steatosis and hepatocellular damage.
• To explore these associations in different alcohol consumption groups.

Main Methods:

• Measured plasma C3a, liver enzymes (AST, ALT, GGT), and estimated liver fat content in 523 individuals.
• Utilized multiple linear regression analyses, stratified by alcohol consumption levels.
• Standardized liver enzymes into a composite LE score.

Main Results:

• C3a showed a significant association with liver fat percentage in both no-to-moderate and heavy alcohol consumers.
• C3a was associated with the liver enzyme score in heavy alcohol consumers but not in the no-to-moderate group.
• A significant interaction (P=0.047) was observed for C3a and liver fat across alcohol consumption levels.

Conclusions:

• Circulating C3a levels, a marker of complement activation, are linked to liver fat content.
• Hepatocellular injury is also associated with C3a levels, especially in individuals with substantial daily alcohol intake.
• Findings highlight the potential involvement of the complement system in alcohol-induced liver disease.