P216 Does mucosal inflammation drive recurrence of PSC in liver transplant recipients with ulcerative colitis?

Abstract

Background: Primary sclerosing cholangitis (PSC) is a progressive fibro-inflammatory disease of the biliary tract. PSC is in 70-80% of the patients associated with a form of IBD, mostly ulcerative colitis (UC). A liver transplantation (LT) remains the only effective treatment for PSC as no disease-modifying treatment is available. After transplant, PSC recurrence (rPSC) occurs in 11-25% of patients. UC is a risk factor for rPSC, and this effect may be attenuated by colectomy, but the mechanism behind this effect is unclear. This study primarily aimed to assess whether mucosal inflammation is a risk factor for developing rPSC. In addition, other patient-and graftrelated risk factors were studied. Methods: In this retrospective cohort study, all UC and non-IBD patients that underwent LT for PSC in the participating hospitals were included. Follow-up started at transplantation and ended at death, rPSC or graft failure due to other causes. The following risk factors were assessed: presence of UC, degree of colonic mucosal inflammation, cytomegalovirus (CMV) infections, recipient age at transplant, gender, gender mismatch and age difference between donor and recipient, rejection, non-heart-beating procedures, (timing of) colectomy, cholangiocarcinoma prior to transplant and type of immunosuppressant drug used. The histological Geboes score was used for assessment of colonic mucosal inflammation. Subsequent Geboes scores were analysed using a Time-Dependent Covariate, which allows for changing scores during follow-up. Right-sided and left-sided inflammation was analysed separately, and the highest score was analysed. Results: In total, 81 patients were included, of which 62 (76.5%) were diagnosed with UC. Seventeen patients (21.0%) developed rPSC during a median follow-up time of 5.2 years. In a subset of 42 patients ( 11 patients with rPSC) colon biopsies were available for analysis of Geboes scores. In this population, no association was found between the degree of mucosal inflammation and rPSC, using both original Geboes scores and a cut-off point of 3. In the full cohort of 81 patients, CMV infections post-LT (HR: 4.576, 95% CI 1.688-12.403) and younger receiver age (age at LT: (HR: 0.934, 95% CI 0.881-0.990)) were independently associated with an increased risk of rPSC, whereas a NHB procedure was not ( HR: 4.258, 95% CI 0.989-18.329, p = 0.052). In univariate analysis, rPSC increased the risk for graft loss (HR: 6.4 95% CI 2.122-19.906, p = 0.001) Conclusions: In this multicentre retrospective cohort study, no association was found between the degree of histological inflammation and occurrence of rPSC. Both a CMV infection post-LT and a younger receiver age at LT are associated with an increased risk of rPSC.