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

Nick Wlazlo*, Marleen M. J. van Greevenbroek, Isabel Ferreira, Eugene H. J. M. Jansen, Edith J. M. Feskens, Carla J. H. van der Kallen, Casper G. Schalkwijk, Bert Bravenboer, Coen D. A. Stehouwer

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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. Materials and methods Plasma C3a, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) were determined in 523 individuals (61% men, age 59 +/- 7years). 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: >30g/day; women: >20g/day). Results C3a was associated with liver fat percentage both in the no-to-moderate (=0 center dot 223; 95%CI 0 center dot 036; 0 center dot 409) and in the heavy alcohol consumers (=0 center dot 632; 95%CI 0 center dot 259-1 center dot 004; P-interaction=0 center dot 047). C3a was also associated with the LE score in heavy alcohol consumers (=0 center dot 917; 95%CI 0 center dot 443-1 center dot 392), but not in no-to-moderate alcohol consumers (=0 center dot 042; 95%CI -0 center dot 198 to 0 center dot 281; P-interaction=0 center dot 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.
Original languageEnglish
Pages (from-to)679-688
JournalEuropean Journal of Clinical Investigation
Issue number7
Publication statusPublished - Jul 2013


  • Alcoholic fatty liver disease
  • complement system
  • nonalcoholic fatty liver disease
  • steatosis


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