Inflammatory bowel disease and primary sclerosing cholangitis: immunological links and clinical outlook

INTRODUCTION: Primary sclerosing cholangitis (PSC) represents a progressive fibroinflammatory cholangiopathy intricately linked to inflammatory bowel disease (IBD), forming a distinctive overlap syndrome driven by immune dysregulation and gut-liver axis disruption and characterized by a markedly increased risk of colorectal and hepatobiliary cancers. AREAS COVERED: This review summarizes current understanding of the immunopathogenesis and clinical spectrum of PSC-IBD. Key mechanisms include aberrant lymphocyte homing through the α4β7/MAdCAM-1 axis, shared genetic susceptibility loci, alterations in bile acid metabolism, and gut microbial dysbiosis. The clinical course and malignancy risk of PSC-IBD are contrasted with those of isolated PSC and IBD, and surveillance strategies are discussed. Therapeutic approaches under investigation, such as advanced therapies and microbiome-targeted interventions including oral vancomycin, are critically appraised based on recent translational and clinical studies. EXPERT OPINION: PSC-IBD demands multidisciplinary, risk-stratified management and intensive cancer surveillance. Although no medical therapy currently halts disease progression, novel agents modulating immune and microbial pathways represent promising avenues. In the future, integration of hepatology, gastroenterology, and immunology within a precision-medicine framework is expected to reshape disease stratification and therapeutic decision-making for this complex overlap syndrome.