Immunometabolic remodeling: new perspectives and strategies for liver transplantation

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.