Liver transplantation remains the definitive treatment for end-stage liver disease, with expanding indications including acute liver failure and transplant oncology. The immunometabolic milieu both systemically and locally in these contexts can diverge from traditional end-stage disease, presenting distinct challenges for immune management. Advances in surgical technique and perioperative care have improved long-term survival, yet extended survival and a larger donor pool have revealed long-term complications such as post-transplant metabolic syndrome. The patient’s systemic metabolic state influences immune cell energy utilization and immunosuppressant metabolism, adding complexity to management. Post-transplant, immune cell subsets exhibit dynamic adaptations in energy metabolism that influence rejection risk, ischemia-reperfusion injury, and the development of immune tolerance. The review confines its scope to mechanisms of immune cell metabolic remodeling and their implications for transplant outcomes. It also discusses translational prospects, including targeting immunometabolic pathways to optimize immunosuppressive regimens, mitigate IRI, and identify non-invasive biomarkers for immune monitoring. Where data are uncertain in the source, this uncertainty is acknowledged. These insights aim to inform strategies to improve long-term outcomes in liver transplant recipients.
Liver transplantation (LT) has become the optimal therapeutic strategy for end-stage liver disease. Beyond chronic conditions, acute liver failure (ALF) and the emerging field of transplant oncology have also become critical indications for LT. It is important to note that the systemic and local immunometabolic states in these specific pathologies may differ significantly from those in traditional end-stage liver disease, presenting unique challenges for immune management. With advancements in surgical techniques and perioperative management, the long-term survival rates of patients have significantly improved. However, extended patient survival and an expanding donor pool have unmasked long-term complications such as post-transplant metabolic syndrome (PTMS). Furthermore, the patient’s systemic metabolic state influences both the metabolism of immune cells and the utilization of immunosuppressants, posing severe challenges to patient management. Studies indicate that following liver transplantation, distinct immune cells undergo dynamic adaptive changes in energy metabolism, which directly determine the outcomes of rejection, ischemia-reperfusion injury (IRI), and immune tolerance. This review systematically elucidates the mechanisms of immune cell metabolic remodeling. Furthermore, it explores the translational prospects of targeting immunometabolic pathways to optimize immunosuppressive regimens, mitigating IRI, and establish non-invasive biomarkers for immune monitoring, ultimately providing new insights for improving the long-term outcomes of liver transplant recipients.