title: Macrophage activation marker soluble CD163 and non-alcoholic fatty liver disease in morbidly obese patients undergoing bariatric surgery.
abstract: OBJECTIVE
  Macrophages play an important role in non-alcoholic fatty liver disease (NAFLD). Soluble CD163 (sCD163) is a specific marker of macrophage activation. We aimed to measure sCD163 in morbidly obese patients with varying degrees of NAFLD before and after bariatric surgery (BS).
  
  
  METHODS
  Demographic, clinical, and biochemical data, and plasma sCD163 measured by enzyme-linked immunosorbent assay, of 196 patients were collected preoperatively and 3, 6, and 12 months after BS leading to significant weight loss. Peroperative liver biopsies were assessed for the NAFLD Activity Score (NAS), Kleiner fibrosis score, and the fatty liver inhibition of progression (FLIP) algorithm. In a subset, CD163 immunohistochemistry and real-time quantitative polymerase chain reaction for CD163 mRNA were performed.
  
  
  RESULTS
  sCD163 was higher in patients with NAS ≥ 5 compared with those with NAS < 5 (2.4(2.0-3.1) vs 1.9(1.5-2.3) mg/L, P < 0.001) and in patients with bridging fibrosis (F ≥ 3) compared with lower fibrosis stages (2.6(2.0-4.9) vs 2.0(1.5-2.4) mg/L, P = 0.001). Preoperative sCD163 was independently associated with both the NAS (P = 0.002) and the fibrosis score (P = 0.024). sCD163 decreased after BS and was greatly reduced after 12 months, more rapidly so in patients with NAS ≥ 5 (P < 0.001) and non-alcoholic steatohepatitis (NASH) according to the FLIP algorithm (P = 0.03). Immunohistochemistry showed CD163-positive macrophages aligning fat-laden hepatocytes and forming microgranulomas in patients with NASH. CD163 mRNA expression did not vary with NAS.
  
  
  CONCLUSIONS
  sCD163 increased in parallel with the severity of NAFLD in morbid obesity, indicating macrophage activation. BS reduced sCD163 even in patients with severe liver injury and fibrosis, suggesting full reversibility of macrophage activation associated with improved insulin sensitivity.
authors.affiliation: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.|INSERM, UMR_S 1166, ICAN, Nutriomics team, Sorbonne Universités, UPMC University, Paris, France.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Kazankov
authors.affiliation: INSERM, UMR_S 1166, ICAN, Nutriomics team, Sorbonne Universités, UPMC University, Paris, France.|Institute of Cardiometabolism and Nutrition, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Joan
authors.initials: J
authors.lastname: Tordjman
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Holger Jon
authors.initials: HJ
authors.lastname: Møller
authors.affiliation: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Vilstrup
authors.affiliation: INSERM, UMR_S 1166, ICAN, Nutriomics team, Sorbonne Universités, UPMC University, Paris, France.|Institute of Cardiometabolism and Nutrition, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Poitou
authors.affiliation: Centre de Recherche Bichat-Beaujon, INSERM U773, University Paris-Diderot, Paris, France.|Pathology Department, Assistance Publique-Hôpitaux de Paris, Beaujon Hospital, Clichy, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bedossa
authors.affiliation: Visceral Surgery Department, Assistance Publique-Hôpitaux de Paris, Ambroise Paré Hospital, Boulogne-Billancourt, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Bouillot
authors.affiliation: INSERM, UMR_S 1166, ICAN, Nutriomics team, Sorbonne Universités, UPMC University, Paris, France.|Institute of Cardiometabolism and Nutrition, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Clement
authors.affiliation: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Henning
authors.initials: H
authors.lastname: Grønbaek
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000097:blood*; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood*; D050110:Bariatric Surgery; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008262:Macrophage Activation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis* / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D009767:Obesity, Morbid / Q000150:complications* / Q000601:surgery*; D059035:Perioperative Period; D011956:Receptors, Cell Surface / Q000097:blood*; D012720:Severity of Illness Index; D012995:Solubility; D013997:Time Factors; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface
keywords: fibrosis; inflammation; macrophages; non-alcoholic steatohepatitis; obesity