Estudo clínico dos marcadores da lesão de isquemia/reperfusão no transplante de fígado - Avaliação do papel da esteatose no enxerto hepático
Arquivos
Data
2007
Autores
Noujaim, Huda Maria 
Orientadores
Montero, Edna Frasson de Souza
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: vários fatores estão associados à lesão de isquemia fria (IF) e referfusão quente
(RQ) no transplante hepático (TxH), tais como infiltrado de neutrófilos e linfo-plasmocitário,
liberação de citoquinas inflamatórias e apoptose. Porém, pouco se conhece sobre o papel da
IF/RQ em enxertos esteatóticos. Objetivo: avaliar o papel da lesão de IF/RQ no TxH em
humanos comparando enxertos esteatóticos e não esteatóticos. Métodos: entre maio/02 e
março/07 foram realizadas 84 biópsias pós reperfusão (2hs após RQ) e 18 pré reperfusão,
totalizando-se 84 TxH em 82 pacientes. As biópsias foram agrupadas em 5 grupos, de acordo
com o grau de macro e microesteatose: GEL – leve (<30%), GEM – moderada (30-59%),
GEG - grave (≥60%), GEA - sem esteatose, GPR-pré-reperfusão. Nas 102 biópsias foram
analisadas: porcentagens de macro e microesteatose, graus de exudato de neutrófilos (0-3) e
infiltrado linfo-plasmocitário portal (0-3), índices de apoptose (métodos de Túnel e Caspase-
3) e de ICAM-1. As esteatoses macro (n=49) e microvesicular (n=74) foram individualmente
analisadas e classificadas em graus leve (G1), moderado (G2) e grave (G3) e ausente (G4).
Resultados: o índice de apoptose (TUNEL) foi: GEL=0.262±0.111, GEM=0.278±0.113,
GEG=0.244±0.117, GEA=0,275±0.094 e GPR=0.181±0.123, p-0.07. No grupo
macroesteatose índice de apoptose (TUNEL) foi: G1=0.284± 0.106, G2+3=0.160±0.109,
G4=0,275±0.094, p-0.05; e no grupo microesteatose, G1=0.222±0.123, G2+3=0.293±0.108,
G4=0.275±0.094, p-0.049. O GEG expressou o ICAM-1 em 83% dos casos de forma difusa.
Não existiu diferença estatística entre os grupos ao analisarmos os índices de apoptose
(caspase-3) e ICAM-1. Conclusão: o GEG e o grupo macroesteatose (moderado e grave)
apresentaram significante redução no índice de apoptose, enquanto o grupo microesteatose
(moderado e grave), significante aumento. E o GEG apresentou expressão de ICAM-1
difusamente, podendo ser estes marcadores envolvidos na lesão de I/R hepática dos enxertos
esteatóticos.
Introduction: many factors are responsable for ischemic/reperfusion (I/R) injury in liver transplant (LTx) as apoptosis. However, the role of I/R injury in steatotic grafts is still unclear. Mains: to analyze the role of I/R in LTx comparing steatotic vs non steatotic graft. Methods: between May/02 and march/07 we performed 84 liver biopsies (2hours) after arterial reperfusion of grafts. Overall we performed 84 LTx in 82 patients.The liver biopsies were divided in 5 groups according with degree of macro and microvesicular steatosis in mild (<30%)-MSG, moderate (30-59%)-MoSG, severe (≥60%) – SSG, absent stetatosis – ASG, before reperfusion – BRG. In 102 liver biopsies were analyzed: percentage of macro and micro steatosis, degree of neutrophils, apoptosis index (TUNEL and Caspase-3) and ICAM-1. Also were analyzed macro and micro steatosis alone and they were classified in different degree MILD (G1), moderate (G2), severe (G3) and absent (G4). Results: the apoptosis index (TUNEL) was: MSG=0.262±0.111, MoSG=0.278±0.113, SSG=0.244±0.117, ASG=0,275±0.094 e BPR=0.181±0.123, p-0.07. The macrosteatosis’ apoptosis index (TUNEL) was G1=0.284± 0.106, G2+3=0.160±0.109, G4=0,275±0.094, p-0.05; and in microsteatosis group - G1=0.222±0.123, G2+3=0.293±0.108, G4=0.275±0.094, p-0.049. There are no statistic difference among the groups when we analyzed apoptosis (caspase-3) and ICAM-1 index. Conclusion: the SSG and macrosteatosis (degree moderate and severe) presented significantly decrease of apoptosis index, probable because these cells died before start apoptotic process. However the microsteatosis (degree moderate and severe) increased apoptotic index associated with I/R injury.
Introduction: many factors are responsable for ischemic/reperfusion (I/R) injury in liver transplant (LTx) as apoptosis. However, the role of I/R injury in steatotic grafts is still unclear. Mains: to analyze the role of I/R in LTx comparing steatotic vs non steatotic graft. Methods: between May/02 and march/07 we performed 84 liver biopsies (2hours) after arterial reperfusion of grafts. Overall we performed 84 LTx in 82 patients.The liver biopsies were divided in 5 groups according with degree of macro and microvesicular steatosis in mild (<30%)-MSG, moderate (30-59%)-MoSG, severe (≥60%) – SSG, absent stetatosis – ASG, before reperfusion – BRG. In 102 liver biopsies were analyzed: percentage of macro and micro steatosis, degree of neutrophils, apoptosis index (TUNEL and Caspase-3) and ICAM-1. Also were analyzed macro and micro steatosis alone and they were classified in different degree MILD (G1), moderate (G2), severe (G3) and absent (G4). Results: the apoptosis index (TUNEL) was: MSG=0.262±0.111, MoSG=0.278±0.113, SSG=0.244±0.117, ASG=0,275±0.094 e BPR=0.181±0.123, p-0.07. The macrosteatosis’ apoptosis index (TUNEL) was G1=0.284± 0.106, G2+3=0.160±0.109, G4=0,275±0.094, p-0.05; and in microsteatosis group - G1=0.222±0.123, G2+3=0.293±0.108, G4=0.275±0.094, p-0.049. There are no statistic difference among the groups when we analyzed apoptosis (caspase-3) and ICAM-1 index. Conclusion: the SSG and macrosteatosis (degree moderate and severe) presented significantly decrease of apoptosis index, probable because these cells died before start apoptotic process. However the microsteatosis (degree moderate and severe) increased apoptotic index associated with I/R injury.