title: Activated complement factor 3 is associated with liver fat and liver enzymes: the CODAM study.
abstract: BACKGROUND
  The complement system may be involved in the pathogenesis of alcoholic and nonalcoholic liver disease, although studies in humans are scarce. For this reason, we investigated whether circulating levels of activated complement factor 3 (C3a) were associated with hepatic steatosis and hepatocellular damage.
  
  
  METHODS
  Plasma C3a, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) were determined in 523 individuals (61% men, age 59 ± 7 years). Liver enzymes (LEs) were standardized and compiled into a LE score. Liver fat content was estimated using a predictive equation that has recently been validated with magnetic resonance spectrometry. Cross-sectional associations between C3a and liver fat or LE s were investigated with multiple linear regression analyses, stratified in no-to-moderate vs. heavy alcohol consumers (men: > 30 g/day; women: > 20 g/day).
  
  
  RESULTS
  C3a was associated with liver fat percentage both in the no-to-moderate (β = 0.223; 95%CI 0.036; 0.409) and in the heavy alcohol consumers (β = 0.632; 95%CI 0.259-1.004; P-interaction = 0.047). C3a was also associated with the LE score in heavy alcohol consumers (β = 0.917; 95%CI 0.443-1.392), but not in no-to-moderate alcohol consumers (β = 0.042; 95%CI -0.198 to 0.281; P-interaction = 0.001).
  
  
  CONCLUSIONS
  C3a levels, as a marker of complement activation, were associated with liver fat content and hepatocellular injury, at least in subjects who consume considerable amounts of alcohol daily.
authors.affiliation: Department of Internal Medicine, Catharina Hospital, Eindhoven, the Netherlands. nickwlazlo@gmail.com
authors.forename: Nick
authors.initials: N
authors.lastname: Wlazlo
authors.forename: Marleen M J
authors.initials: MM
authors.lastname: van Greevenbroek
authors.forename: Isabel
authors.initials: I
authors.lastname: Ferreira
authors.forename: Eugene H J M
authors.initials: EH
authors.lastname: Jansen
authors.forename: Edith J M
authors.initials: EJ
authors.lastname: Feskens
authors.forename: Carla J H
authors.initials: CJ
authors.lastname: van der Kallen
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
authors.forename: Bert
authors.initials: B
authors.lastname: Bravenboer
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000428:Alcohol Drinking; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D003167:Complement Activation / Q000502:physiology*; D015926:Complement C3a / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005234:Fatty Liver / Q000201:enzymology* / Q000378:metabolism; D005235:Fatty Liver, Alcoholic / Q000201:enzymology* / Q000209:etiology / Q000378:metabolism; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D011446:Prospective Studies; D012044:Regression Analysis; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D015415:Biomarkers; D015926:Complement C3a; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase