Perihilar cholangiocarcinoma: Expanding the role of liver transplantation in the era of multimodal therapy.

Perihilar cholangiocarcinoma (pCCA) accounts for approximately 50% of all cholangiocarcinomas and carries a dismal prognosis owing to late diagnosis and high post-resection recurrence rates. Over the past two decades, liver transplantation (LT) following neoadjuvant therapy according to the Mayo Criteria has yielded acceptable long-term survival in highly selected patients with unresectable pCCA, establishing LT as an established treatment option. Nevertheless, substantial challenges remain, including tumor progression on the waiting list, intolerance to neoadjuvant therapy, and postoperative complications from prior chemoradiation. Moreover, pCCA recurrence is closely linked to post-transplant immunosuppressive management, and minimizing long-term immunosuppression may be critical. This review analytically examines the current role of LT for pCCA, emphasizing patient selection, standardized neoadjuvant regimens, immunological considerations, and favorable prognostic factors. The emerging potential and risks of incorporating immune checkpoint inhibitors in the pre-transplant setting are also explored. By synthesizing available evidence, we aim to define the clinical contexts in which LT may confer durable benefit and to highlight the key obstacles limiting its broader application.