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ADTU-04 Faecal calprotectin in PSC-IBD: a novel marker of cholangitis
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  1. Polychronis Pavlidis,
  2. Yasser El-Sherif,
  3. Ben Warner,
  4. Shraddha Gulati,
  5. Konstantinos Sarras,
  6. Ellie Alberts,
  7. Joe Segal,
  8. Tamir Rashid,
  9. Phil Harrison,
  10. John Devlin,
  11. Michael Heneghan,
  12. Alberto Fueyo,
  13. Gwion Emlyn,
  14. Hadil Abu Arqoub,
  15. Patrick Dubois,
  16. Deepak Joshi,
  17. Nick Powell,
  18. Bu’ Hayee
  1. King’s Health Partners, London, UK

Abstract

Introduction Primary sclerosing cholangitis (PSC) is a chronic inflammatory condition of the bile ducts leading to fibrosis and end stage liver disease. A lack of robust non-invasive biomarkers has been hindering disease monitoring and development of optimal therapies. We have previously noted that the high levels of faecal calprotectin (fcal) seen in PSC-IBD patients belie the mild or quiescent intestinal inflammation. An unsupervised proteomics study identified biliary calprotectin as a potential biomarker. Here, we test the hypothesis that fcal is a marker of biliary injury in PSC.

Methods We analysed paired endoscopic activity data (UCEIS) and fcal results of patients with PSC-IBD (n=20) or UC (n=20) who underwent colitis surveillance in the context of a colitis surveillance pilot study. Relevant clinical data was recorded prospectively. Recruiting consecutive patients attending for ERCP (n=6) allowed for the concomitant testing of biliary and faecal calprotectin.

Results As expected, fcal strongly correlated with severity of mucosal injury (UCEIS) in UC [r=0.82, 95% CI(0.58, 0.92), p<0.0001]. However, the correlation was weaker in PSC-IBD [r=0.59, 95% CI(0.19, 0.82), p=0.006]. Moreover, in patients with PSC-IBD and quiescent colitis (UCEIS: 0–1) fcal concentration was significantly higher in comparison to UC patients with comparable endoscopic activity [279 ug/g (10, 1560) vs. 30 (10, 161), p=0.015)]. A trend towards abnormal liver biochemistry was seen in those PSC-IBD with higher fcal [ALP: 250IU/L (113, 561) vs. 83 (59, 170), p=0.06, GGT: 351 U/L (117, 1014) vs. 51 (29, 153) p=0.02, AST: 53 U/L (26, 85) vs. 37 (22, 43), p=ns]. UC patients with quiescent colitis and fcal >150 had a higher risk of colitis relapse in 12 months [HR=7.6, 95% CI(1.8, 33.6)] in comparison to those with fcal <150. However, in patients with PSC-IBD and quiescent colitis a fcal >150 was associated instead with a higher risk of cholangitis associated complications (need for antibiotics or stent insertion), HR=6.5, 95% CI(1.3, 33.9). Strikingly, biliary calprotectin concentration showed a strong correlation with fcal concentration (r=0.90, p=0.04). Interestingly, immunostaining of biliary brushings for calprotectin demonstrated positive staining in cholangiocytes as well as neutrophils and macrophages.

Conclusion In patients with PSC-IBD and quiescent colitis the identification of a raised fcal is likely to herald complications of inflammation in the bile ducts rather than the colon. In this setting, fcal may be a valuable prognostic biomarker of cholangitis. Additionally, our data suggest that in PSC, the source of raised fcal may also be the damaged biliary epithelium.

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