Prevalence and long-term outcome of sub-clinical primary sclerosing cholangitis in patients with ulcerative colitis

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, 70 patients with UC and normal liver function (51 extensive UC, 19 CRD), 28 healthy volunteers (negative controls) and 28 patients with PSC and cholestasis (positive controls) underwent MRC and blood evaluation. MRC scans were interpreted blindly by two radiologists who graded individually, the scans as definitive for PSC, possible for PSC or normal. Clinical outcome was assessed by blood monitoring, abdominal imaging and endoscopic surveillance. Results 7/51 (14%) with extensive UC and 4/19 (21%) 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 = .04), non-smoking (P = .03), pANCA (P = .04), quiescent colitis (P = .02), absence of azathioprine (P = .04) and high-grade CRD (P = .03). Inter-observer (kappa = 0.88) and intra-observer (kappa = 0.96) agreement for MRC interpretation was high. No negative controls were assessed as definite PSC, 4/28 were considered on blinding as possible PSC. During follow-up of sub-clinical PSC (median 10.1(3.1-11.9) years), four patients developed abnormal liver biochemistry, two had radiological progression of PSC and seven developed malignancy, including two biliary and one 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.