2010 - TTS International Congress


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Liver Donor Allocations

48.4 - Evaluation of the mechanisms of cold ischemia / warm reperfusion injury in human liver transplantation comparing macrosteatotic and no steatotic grafts.

Presenter: HUDA, NOUJAIM, SÃO PAULO, Brazil
Authors: NOUJAIM H., Montero E., Ribeiro C., Cappellozi V., Crescentini F., dos Santos R., Motta L., BRANEZ J., SANTANA C., de Miranda M., Genzini T.

EVALUATION OF THE MECHANISMS OF COLD ISCHEMIA / WARM REPERFUSION INJURY IN HUMAN LIVER TRANSPLANTATION COMPARING MACROSTEATOTIC AND NO STEATOTIC GRAFTS.

LIVER - DONOR ALLOCATIONS

H.M. Noujaim1, E.F.S. Montero2, C.M.D.F. Ribeiro3, V.L. Cappellozi4, F. Crescentini1, R.G. Dos santos1, L.T. Motta1, J.R. Branez1, C.D.S. Santana1, M.P. De miranda1, T. Genzini1
1Hepato, Hospital Beneficencia Portuguesa São Paulo / Hospital Bandeirantes, São Paulo/BRAZIL, 2Cirurgia Experimental, EPM / UNIFESP, São Paulo/BRAZIL, 3Cip, Hospital Beneficencia Portuguesa de São Paulo, São Paulo/BRAZIL, 4Lab Imunopatologia, FMUSP, São Paulo/BRAZIL

Body: Introduction – Apoptosis is a key mechanism of reperfusion injury in normal liver; however, the pathway of cell death in steatotic grafts after liver transplant (LTx) is unknown. Purpose – to analyze the mechanisms and the evolution of the cold ischemia and warm reperfusion injury (CI/WR) in human LTx, when macrosteatotic grafts were used. Patients and methods – this is a prospective study performed between May/02 and Feb/10 which 182 liver biopsies were collected: 91 on back table (pre reperfusion) and other 91 at 2 hours after graft reperfusion (pos reperfusion). It was analyzed donors’ demographics date, cold (CIT) and warm ischemic time (WIT) and preservation solutions. The liver biopsies were assessed for the following histological features (hematoxylin-eosin HE): parenchymal neutrophilic infiltration (degree 0- absent, I –rare around zone 3, II-moderate in zone 3, III- since zone 3 to1), portal inflammation (degree 0 - absent, I- mild, II- moderate, III– severe), hepatocellular necrosis, ballonization and presence of apoptotic cells; steatosis was classified in macro and/or microvesicular, and its degree classified as : AG- absent (<5%), MiG-mild (5 to 29%), MoSG- moderate (30 to59%), severe(≥60%). Apoptosis was assessed by the apoptosis index (TUNEL and Caspase-3 cleaved assays). Results significant when p<0.05. Results – There are no statistics difference among 3 groups (AG vs MiG vs MoSG) regarding donors’ age, causes of death, days in ITU, ALT and sodium serum; except body mass index (BMI): AG - 24±3.5, MiG- 26±3.2, MoSG - 27±4.3 (p-0.01) and AST (U/l):AG -83±73, MiG - 52±29, MoSG - 121±123 (p-0.05). The CIT and WIT (min) were in AG, MiG, MoSG, respectively: 549±146, 528±102, 495±122min (p-0.5) and 41±7, 38±7.5, 41±5min (p-0.3). After reperfusion the mean of hepatocellular necrosis was in AG – 2.5±5, MiG - 7±11, MoSG - 16±19, (p<0.001).The results of pre and pos reperfusion liver biopsies are on table below. Conclusion – Before graft reperfusion, there was exponential raise of neutrophil parenchyma infiltration and hepatocellular necrosis regarding increase the macrosteatosis degree. Also, after reperfusion the grafts (>30% macrosteatosis) presented significant enlarging of hepatocellular necrosis and impairment of apoptosis index (TUNEL). However, research must be done to better understand the mechanisms of I/R injury in human macrosteatotic grafts and, consequently to transplant these grafts safely.

MacrosteatosisDegree Absent (n=61) Mild (n=21) Mod+Sev (n=5+4) P
Pre Reperfusion Neutrophil Infiltration(I) Hepatocellular Necrosis (I+II) 27(44%) 1 (2%) 12 (57%) 2(9.5%) 6(67%) 1(11%) <0.001 0.02
Pos Reperfusion Hepatocellular Necrosis(I+II) Apoptosis index(TUNEL) 18(29%) 0.23±0.10 9(43%) 0.20±0.12 6(67%) 0.13±0.07 0.006 0.2

Disclosure: All authors have declared no conflicts of interest.


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