title: Inflammation But Not Biliary Obstruction Is Associated With Carbohydrate Antigen 19-9 Levels in Patients With Primary Sclerosing Cholangitis.
abstract: OBJECTIVE
  Assays that measure the serum level of carbohydrate antigen 19-9 (CA19-9) are used to screen patients with primary sclerosing cholangitis (PSC) for malignancies. However, in patients with PSC, cholestasis, and bacterial cholangitis, the CA19-9 level can be affected by variants in the fucosyltransferases 2 and 3 genes (FUT2 and FUT3), which regulate the production of CA19-9. We investigated how these genotypes affect cancer screening in these patients.
  
  
  METHODS
  We performed a retrospective analysis of data from 209 patients with PSC (19 patients with biliary malignancy, 23 patients with cholestasis and bacterial cholangitis) treated at the University Hospital Heidelberg from 1987 through 2014. We collected data on the maximum serum level of CA19-9; laboratory measures of cholestasis or inflammation; the presence of dominant stenosis, cholestasis, and bacterial cholangitis; and FUT2 and FUT3 genotypes. Patients were assigned to intermediate (n = 161) or high (n = 48) CA19-9 biosynthesis groups, based on FUT2 and FUT3 genotypes. Patients incapable of CA19-9 biosynthesis, based on genetic features, were excluded.
  
  
  RESULTS
  The median level of CA19-9 was 31.1 U/mL in cancer-free patients. The CA19-9 level correlated with the level of C-reactive protein (P < .001); high CA19-9 biosynthesis correlated with high leukocyte counts (P = .037), but not intermediate CA19-9 biosynthesis. There was no correlation between the level of CA19-9 and laboratory markers of cholestasis. The level of CA19-9 was the lowest in patients without biliary obstruction, cholestasis, or bacterial cholangitis (7.8 U/mL), followed by patients with only obstruction (28.0 U/mL), and then patients with cholestasis and bacterial cholangitis (77.0 U/mL and 205.4 U/mL in patients without or with concomitant obstruction, respectively). The greatest increase in CA19-9 as a result of cholestasis and bacterial cholangitis was observed in patients in the high CA19-9 biosynthesis group.
  
  
  CONCLUSIONS
  In patients with PSC, cholestasis has little effect on the level of CA19-9, but cholestasis and bacterial cholangitis increase the level. Their effects on CA19-9 level depend on the FUT2 and FUT3 genotype. These findings support the analysis of FUT2 and FUT3 genotype during follow-up evaluation of patients with PSC.
authors.affiliation: Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Wannhoff
authors.affiliation: Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Rupp
authors.affiliation: Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Kilian
authors.initials: K
authors.lastname: Friedrich
authors.affiliation: Department of Internal Medicine I and Clinical Chemistry, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Maik
authors.initials: M
authors.lastname: Brune
authors.affiliation: Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Knierim
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany; Liver Cancer Center Heidelberg, University of Heidelberg, Heidelberg, Germany.
authors.forename: Christa
authors.initials: C
authors.lastname: Flechtenmacher
authors.affiliation: Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Sauer
authors.affiliation: Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany; Liver Cancer Center Heidelberg, University of Heidelberg, Heidelberg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stremmel
authors.affiliation: Norwegian Primary Sclerosing Cholangitis Research Center, Research Institute of Internal Medicine and Section of Gastroenterology, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; K.G. Jebsen Inflammatory Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Hov
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany; Liver Cancer Center Heidelberg, University of Heidelberg, Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.affiliation: Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany; Liver Cancer Center Heidelberg, University of Heidelberg, Heidelberg, Germany.
authors.forename: Karl Heinz
authors.initials: KH
authors.lastname: Weiss
authors.affiliation: Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany; Liver Cancer Center Heidelberg, University of Heidelberg, Heidelberg, Germany. Electronic address: Daniel_Gotthardt@med.uni-heidelberg.de.
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Gotthardt
mesh_terms: D000328:Adult; D018395:CA-19-9 Antigen / Q000097:blood*; D015209:Cholangitis, Sclerosing / Q000175:diagnosis* / Q000473:pathology*; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics; D005838:Genotype; D005858:Germany; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D044967:Serum / Q000737:chemistry; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D018395:CA-19-9 Antigen; D005647:Fucosyltransferases; D000097631:Galactoside 2-alpha-L-fucosyltransferase; C019818:3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase
keywords: Acute Cholangitis; Biomarker; CRP; Fucosyltransferase