Hepatocellular Expression of Macrophage Migration Inhibitory Factor (MIF) Is Associated with Ischemia-Reperfusion Injury After Liver Transplantation

Introduction:  Ischemia-reperfusion injury (IRI) is a major determinant of initial graft function after liver transplantation (LT), directly influencing the incidence of early dysfunction and short-term clinical outcomes. Macrophage migration inhibitory factor (MIF), a pleiotropic cytokine involved in inflammatory pathways and mechanisms of cellular adaptation to oxidative stress, may play a modulatory role in IRI, although its immediate tissue behaviour in grafts remains poorly characterised.

Methods:  We retrospectively evaluated adult LT recipients who underwent post-reperfusion biopsies suitable for histological and immunohistochemical analysis. Immunohistochemical expression of MIF was quantified using the IHC Profiler plugin (ImageJ), whereas IRI was graded according to validated histopathological criteria.

Results:  Among 153 biopsies analysed, 103 met the eligibility criteria, with most cases showing absent or mild IRI (70.9%). Hepatocellular expression of MIF was predominantly weak or moderate. Stronger immunohistochemical staining for MIF was associated with lower IRI severity (p<0.05). MIF expression correlated with pre-transplant laboratory parameters, without association with steatosis or early outcomes, including retransplantation or death within 15 days.

Conclusion:  The findings suggest that greater immunohistochemical expression of MIF at reperfusion is associated with lower IRI intensity, indicating a possible adaptive role for this cytokine during this critical phase. MIF emerges as a potential tissue marker complementary to traditional histopathological scoring, with relevance for graft assessment and use in contemporary liver perfusion strategies.

Keywords:
Liver Transplantation; Reperfusion Injury; Immunohistochemistry; Macrophage Migration Inhibitory Factors