Revista do Colégio Brasileiro de Cirurgiões
http://www.rcbc.periodikos.com.br/article/doi/10.1590/0100-6991e-2026002925
Revista do Colégio Brasileiro de Cirurgiões
Artigo Original

Expressão hepatocitária do Fator Inibitório da Migração de Macrófagos (MIF) está associada à lesão de isquemia-reperfusão após transplante hepático

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

Rodrigo Humberto Vilar Pontes Filho; Camila Xavier Brito; Serena Dáfne do Carmo Silva; Agnaldo Soares Lima; Francisco Guilherme Cancela e Penna; Fernanda Maria Farage Osório; Níkolas Knupp Thome; Cristiano Xavier Lima; Paula Vieira Teixeira Vidigal

http://dx.doi.org/10.1590/0100-6991e-2026002925 RCBC, vol.53, e2026002925, 2026
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Resumo

Introdução: A lesão de isquemia-reperfusão (LIR) é um evento determinante da função inicial do enxerto após o transplante hepático (TH). O fator inibitório da migração de macrófagos (MIF) é uma citocina pleiotrópica envolvida em vias inflamatórias e em mecanismos de adaptação celular ao estresse oxidativo. Embora possa exercer papel modulador na LIR, sua expressão tecidual imediata em enxertos hepáticos permanece pouco caracterizada.

Métodos: Este estudo retrospectivo avaliou receptores adultos submetidos a transplante hepático, com análise histológica e imuno-histoquímica de biópsias obtidas após a reperfusão. A expressão de MIF foi quantificada por meio do plugin IHC Profiler (ImageJ), enquanto a LIR foi graduada segundo critérios histopatológicos validados.

Resultados: Entre 153 biópsias analisadas, 103 preencheram os critérios de elegibilidade, com predomínio de LIR ausente ou leve (70,9%). A expressão hepatocitária de MIF foi predominantemente fraca ou moderada. Marcações mais intensas de MIF associaram-se a menor gravidade da LIR (p < 0,05). A expressão de MIF correlacionou-se com parâmetros laboratoriais pré-transplante, sem associação com esteatose ou com desfechos precoces, incluindo retransplante ou óbito em até 15 dias.

Conclusão: Esses achados sugerem que maior marcação tecidual de MIF no momento da reperfusão relaciona-se a menor intensidade da LIR, indicando possível papel adaptativo dessa citocina nessa fase crítica. O MIF desponta como potencial marcador tecidual complementar ao escore histopatológico tradicional, com relevância para a avaliação de enxertos e para o desenvolvimento de estratégias contemporâneas de perfusão hepática.

Palavras-chave

Transplante de Fígado; Lesão por Isquemia-Reperfusão; Fator Inibidor da Migração de Macrófago  

Abstract

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  

Referências

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Submetido em:
22/09/2025

Aceito em:
05/05/2026

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