Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive biliary inflammation and fibrosis. PSC has a strong association with inflammatory bowel disease (IBD), which is diagnosed in 60-80% of patients. The coexistence of the PSC and IBD increases the risk for colorectal cancer (CRC). Furthermore, PSC predisposes to the occurrence of other neoplastic conditions, such as cholangiocarcinoma (CCA), gallbladder, and hepatocellular carcinoma. The pathogenesis of PSC is still unclear. Current evidence supports a multifactorial etiology, where genetic predisposition, altered gut microbiota, and immune-mediated phenomena play a crucial role. The highly variable natural history of PSC, with possible intercurrent clinical events (e.g., cholangitis, biliary lithiasis) that could be dissociated from the severity of underlying liver disease with consequent fluctuant clinical symptoms and serum cholestasis marker, makes the prognostic assessment of these patients challenging. To date, no effective medical therapy has been registered, and liver transplantation is the only therapeutic option in patients developing end-stage liver disease. In this chapter, we describe epidemiological and clinical features of PSC, current understanding of its pathogenesis, and address challenges and opportunities associated with its management while focusing on risk stratification.