Edad Donantes

RECEPTORES DONANTES INJERTOS LÍMITES SON MÁS SENSIBLES A LA LESIÓN POR ISQUEMIA/REPERFUSIÓN!!! DESEQUILIBRIO ENTRE ÓRGANOS DISPONIBLES Y CANDIDATOS PARA TRASPLANTE HEPÁTICO EDC grafts might be defined as grafts at increased risk for poor function or failure that subject the recipient to greater risks of morbidity and mortality. There is no consensus though about the specific factor or factors that define a graft as marginal or about which combinations of factors should exclude these grafts from use because of unacceptable risk to the recipient overall,or more specifically to a particular recipient, most likely a high risk recipient. Indeed, it is now clear that extended criteria donors might work perfectly if placed into the appropriate recipient. The outcome of ECD grafts must be optimized by minimizing the cold ischemic time. 2 2

Influencia del uso de donantes con criterios expandidos en el desarrollo de DPI (lesión preservación) PI grave It is interesting to note that PI, in turn, has been associated with a number of donor factors, including donor age, moderate to severe steatosis, cold ischemia time or prolonged stay in ICU. In this study by Briceño and col, only 33% of patients without any of these donor factors developed PI. In contrast, 47% of those with 1 DF, 66% of those with 2 factors and 78% of those with more than 3 factors developed this complication. Factores donante: Uso drogas inotrópicas a altas dosis (OR=1.56) Edad Donante (OR=1.017 per yr) Esteatosis moderada-severa (OR=3.63) Tiempo isquemia frio (OR=1.109 per hr) Estancia UCI prolongada (OR=1.79) Briceño, Transpl 2002 3

Pre-LT injury Post-LT injury Optimal Post-LT damage Peri- operative Organ quality Post-LT damage Peri- operative damage Donor quality So based, on all these data, one can hypothesize that grafts from marginal donors may be particularly sensitive towards additional injuries before and after transplantation. The quality of the graft is influenced by various risk factors including donor age, previouos diseases (such as NASH or HCV..), the consequences of brain or to a lesser extent cardiac death and the volume. Further perioperative damages resulting from operative manipulations during the harvesting procedure and consequences of ischemia/reperfusion injury may damage grafts from marginal donors more than those from optimal donors. Finally, after transplantation, additional injuries such as rejection, viral infections...mau also have a stronger impact on marginal grafts with the consequence of reduced long-term function. Ischemia/reperfusion injury Age Previous diseases (steatosis, ...) Brain / Cardiac death Volume (split/LDLT ?) Alloantigenic specific and unspecific events: Rejection, drug toxicity, viral infection.... 4

Máquinas Preservación Guarrera J, LT 2012 VENTAJAS DE LA MAQUINA DE PRESERVACIÓN FRENTE A LA PRESERVACIÓN EN FRIO CONVENCIONAL 5

Rechazo Agudo 6

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Progresión del estadio de fibrosis post-THO: efecto de los bolos de metil-prednisolona 4 p=0,03 Nº bolos de MP > 3 3 2 Nº bolos de MP: 0 - 3 Varios estudios como este han demostrado que la utilización de bolos de MP, es decir la administración repentina de dosis masivas de corticoides es negativa para la evolución de la hepatitis C post.trasplante, y en esta diapo vemos como la progresion histologica es mayor en aquellos que reciben mas de 3 bolos de MP. 1 0 1 2 3 4 5 6 7 Años desde el trasplante Berenguer M, J Hepatol 2000 8

Hepatitis C vs. Rechazo 9

Hepatitis C y Rechazo 10

Hepatitis C y Rechazo Demetris, LT 2010; Hubscher SG, J Hepatol 2011

Donante (D) o Receptor (R) Seropositividad (+/-) Infección CMV RIESGO Donante (D) o Receptor (R) Seropositividad (+/-) Alto D+/R- Intermedio D+/R+, D-/R+ Bajo D-/R- CMV INFECTION CMV DISEASE Increasing viral load Fishman JA et al. Cytomegalovirus in transplantation – challenging the status quo. Clinical Transplantation. 2007;21:149-158. 12

«Preemptive therapy» Fishman JA et al. Cytomegalovirus in transplantation – challenging the status quo. Clinical Transplantation. 2007 13

Causas de hepatitis crónica injerto Hepatitis viral enfermedad AI Recurrencia enfermedad no AI Recurrencia AI de novo ???? (rechazo tardío,….) Hubscher SG, J Hepatol 2011

Recurrencia de enfermedades “AI”: CBP, CEP, HAI Pronóstico excelente con supervivencia a 5 años del 80%-95% Tasas de recurrencia: CBP: 20% en 5 años CEP: 20% en 5 años AI Hepatitis:  con seguimiento (8%, 20% y 68% al 1, 3 y 5 años) Difficultades en establecer el diagnóstico correcto No siempre evidencia de recurrencia analíticamente

Hepatitis Autoinmune «de novo» Inflamación portal con múltiples células plasmáticas. Hepatitis de interface prominente Inflamación lobular con zonas de necrosis. Similar a recurrencia HAI con cambios hx compatibles, hipergammaglobulinemia con aumnento de IgG en suero y presencia de autoac. Respuesta aloinmune, ej. Mismatch en el genotipo de la glutation S transferasa entre D y R (un 20% de caucasicos no tienen el gen que codifica la GSTT1). Pero tb se ha visto este proceso en ausencia de este mismatch. Neuberger J, J Hepatol 2013 (en prensa) 16