Prevalence and Long-Term Outcome of Sub-Clinical Primary Sclerosing Cholangitis in Patients with Ulcerative Colitis

Abstract

Background: Primary sclerosing cholangitis (PSC) is closely associated with inflammatory bowel disease, particularly ulcerative colitis (UC), with an increased risk of biliary and colorectal malignancy. We sought to clarify the prevalence, characteristics and long-term outcome of sub-clinical PSC diagnosed by magnetic resonance cholangiogram (MRC) in patients with UC and normal liver biochemistry, with or without colorectal dysplasia (CRD). Methods: In this prospective case-control study, 68 patients with UC and normal liver function (51 extensive UC, 17 CRD), 28 healthy volunteers (negative-controls) and 28 patients with PSC and cholestasis (positive-controls) underwent MRC and blood evaluation. MRC scans were interpreted by two blinded radiologists. Clinical outcome was assessed by blood monitoring, abdominal imaging and endoscopic surveillance. Results: 7/51 (14%) with extensive UC and 4/17 (24%) with CRD had biliary abnormalities on MRC consistent with PSC. 7/11 (64%) with sub-clinical PSC had isolated intrahepatic duct involvement. Sub-clinical PSC was associated with advanced age (p=0.04), non-smoking (p=0.03), pANCA (p=0.04), quiescent colitis (p=0.02), absence of azathioprine (p=0.04), and high-grade CRD (p=0.03). Inter-observer (kappa=0.88) and intra-observer (kappa=0.96) agreement for MRC interpretation was high. During follow-up of sub-clinical PSC (median 10.1(3.1-11.9) years), 36% developed abnormal liver biochemistry, 18% had radiological progression of PSC and 64% developed malignancy, including 2 biliary and 1 colorectal carcinoma. Conclusions: Prevalence of sub-clinical PSC appears high in patients with extensive UC and normal liver biochemistry, with or without CRD. Disease progression and malignancy were identified on long-term follow-up. MRC should be considered for all patients with extensive UC or CRD to stratify surveillance. Funding Statement: Funding for this project was provided from Oxfordshire Health Services Research Committee (Grant 0851) and the Oxford Radcliffe Hospitals Charitable Fund for PSC (Grant 0528). This work was supported by the NIHR Biomedical Research Centre, based at Oxford University Hospitals Trust, Oxford. Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: Ethical approval was granted from the Oxfordshire Research Ethics Committee (Extensive UC cohort: 05/Q1606/151 and CRD cohort: 09/H0607/4). Written informed consent was obtained from each patient and control for this study.