Epidemiology, Risk Factors and Pathophysiology of Primary Sclerosing Cholangitis in Inflammatory Bowel Disease: An Update

ABSTRACT Background and Aims Primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) represent a unique clinical syndrome affecting up to 80% of PSC patients, characterised by distinct epidemiological patterns, pathophysiological mechanisms and clinical outcomes that differ substantially from either condition occurring independently. This review aims at elucidating the complex clinical landscape of PSC–IBD. Methods A comprehensive literature search was conducted using MEDLINE, EMBASE and Cochrane Library databases until August 2025, focusing on PSC–IBD epidemiology, risk factors, pathophysiology, natural history and clinical management. Evidence synthesis leverages narrative review methodology given the study heterogeneity. Results PSC–IBD demonstrates striking geographic clustering in northern latitudes with annual incidence of 0.87 per 100,000 and prevalence of 13.53 per 100,000 globally. Male predominance characterises the condition (51%–72%), with diagnosis occurring more often between ages 40–59 years. The intestinal involvement usually exhibits extensive colonic involvement with typical rectal sparing (5.6%–66.4%), right‐sided predominance and paradoxically, mild clinical manifestations despite active inflammation found at endoscopy. Pathogenesis involves an intricate interplay between genetic predisposition, gut microbiome dysbiosis, compromised intestinal barrier function and aberrant lymphocyte trafficking through the gut–liver axis. Clinical outcomes are influenced by diagnostic sequence, with IBD diagnosis preceding PSC conferring worse transplant‐free survival (HR 1.34, 95% CI 1.02–1.75). Colectomy timing impacts post‐transplant outcomes, with pre‐transplant colectomy conferring protection against recurrent PSC (HR 0.65, 95% CI 0.42–0.99). Oral vancomycin has shown promising effects on IBD activity in PSC–IBD, with improved clinical remission (adjusted OR 5.24) and endoscopic remission (adjusted OR 2.76) in paediatric cohorts. Patients face significantly elevated malignancy risks, including 3 to 5‐fold increased colorectal cancer incidence (cumulative risk 13% at 30 years) and hepatobiliary malignancies with incidence rates of 7.16, 2.19, and 1.52 per 1000 person‐years for cholangiocarcinoma, hepatocellular carcinoma and gallbladder cancer respectively. Conclusions PSC–IBD represents a distinct clinical entity requiring specialised multidisciplinary management. Current therapeutic options remain limited, with liver transplantation representing the only curative treatment for advanced disease. Understanding the unique epidemiological and pathophysiological features of this condition is essential for optimising patient outcomes and developing targeted therapeutic interventions.