Beyond the Graft: Optimizing Post-Transplant Care in Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by fibro-inflammatory lesions of the biliary tree. In the absence of available, effective medical therapies, many patients progress to liver failure, making PSC one of the leading indications for liver transplantation (LT), despite its rarity. While LT in PSC is associated with good overall short- and long-term survival, post-transplant outcomes are limited by recurrent PSC (rPSC), which affects up to one quarter of PSC recipients with a significant risk of graft loss and re-transplantation. The risk of rPSC reflects a complex interaction between donor and recipient factors including associated inflammatory bowel disease (IBD), and long-term exposure to immunosuppression. Therefore, post-transplant management requires an individualized multidisciplinary approach and tailored immunosuppressive regimens aimed at balancing the risk of rejection and rPSC with the risk of infection and malignancy. Optimal control of IBD has emerged as a key modifiable determinant of rPSC risk and post-transplant outcomes. In addition, patients with PSC, particularly PSC-IBD patients, carry a significantly increased risk of hepatobiliary and colorectal cancer. Importantly, this oncological risk persists after LT. Thus, long-term, structured cancer surveillance must remain an integral component of post-transplant care. Looking ahead, novel therapies targeting shared hepatic and intestinal fibro-inflammatory pathways are currently being investigated to modify disease activity in the pre-transplant setting. Future studies are needed to assess whether these agents might be applicable also in the post-transplant setting to improve long-term graft and patient survival.