Role of efferocytosis in liver transplantation via hepatic macrophage

Liver transplantation has undergone progressive advancements since the 1960s, with optimized surgical techniques and improved outcomes resulting from standardized procedures and therapeutic regimens. However, postoperative complications-such as ischemia-reperfusion injury, acute rejection, hepatocellular carcinoma recurrence, and biliary injury-continue to significantly affect both survival rates and quality of life in liver transplant recipients. Efferocytosis, the phagocytic clearance of apoptotic cells, plays a critical role in preventing necrosis-induced inflammation and promoting tissue resolution and repair. Accumulating evidence suggests that impaired efferocytosis is associated with several complications following liver transplantation. Although multiple hepatic cell types participate in efferocytosis, macrophages-notably Kupffer cells and monocyte-derived macrophages-are the primary mediators responsible for clearing apoptotic cells in the liver. Nevertheless, significant gaps remain in our understanding of how hepatic macrophages perform efferocytosis and whether defects in this process within donor-derived macrophages exacerbate post-transplant complications. This review provides a comprehensive discussion of efferocytosis, with a focus on its impact on liver transplantation-related complications. Furthermore, we explore the potential of targeting efferocytosis as a novel therapeutic strategy in liver transplantation.