The new landscape of liver transplantation: Evolving candidates, new technologies, and personalized care

Liver transplantation (LT) is entering a new era shaped by changes in disease epidemiology, candidate complexity, donor utilization, and post-transplant management. The decline of viral hepatitis-related cirrhosis, together with the rise of metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, and hepatocellular carcinoma, has transformed the LT waitlist into an older, frailer, and more cardiometabolically complex population. At the same time, donation after circulatory death and machine perfusion are expanding the donor pool and redefining the boundaries of graft suitability. Candidate selection is also moving beyond traditional diagnosis-based criteria, with increasing acceptance of early LT for carefully selected alcohol-related liver disease, utility-based transplantation for acute-on-chronic liver failure, and biology-driven transplant oncology, in which HCC is established whereas selected iCCA and unresectable CRLM indications remain investigational. In parallel, artificial intelligence and machine learning are being developed as decision-support tools for candidate assessment, waitlist prioritization, donor-recipient matching, and prediction of post-transplant outcomes; prospective validation and evidence of clinical impact remain limited. Immunosuppression is facing a similar transformation, shifting from standardized lifelong exposure toward individualized, monitored minimization and immunologic risk profiling, while complete withdrawal and operational tolerance remain restricted to highly selected recipients within specialized protocols. In this Perspective, we argue that the future of LT will depend on integrating biological reserve, disease behavior, graft quality, and expected survival benefit into transparent, multidisciplinary decision-making. The central challenge will be to translate innovation into durable clinical benefit while preserving equity in access to transplantation.