Objectifs - Evaluation d'une nouvelle technique de transplantation hepatique chez le porc dans le but de permettre la survie et la regeneration d'un petit greffon par l'apport d'un flux veineux portal adapte et controle. Materiels et methodes - Vingt porcs Large-White ont recu une transplantation hepatique heterotopique apres une anastomose mesenterico-cave terminalisee dans un rapport de poids donneur/receveur en dessous de 30 %. Elle a ete associee a des ligatures de la veine porte et du choledoque du receveur dans le hile et de la veine mesenterique superieure en aval du shunt. Dans une serie temoin (n = 5), il n'a pas ete fait d'anastomose mesenterico-cave terminalisee et le greffon recevait tout le sang veineux splanchnique. Resultats - L'anastomose mesenterico-cave terminalisee a permis de deriver 60 % du flux splanchnique. Les porcs de l'etude ont eu une mediane de survie de 39 jours (extremes : 8-98). La bilirubinemie mediane a 1 semaine a ete de 12 μmol/L (extremes: 4-59). A l'autopsie, l'hypertrophie des greffons dont l'aspect histologique etait normal, a ete en moyenne de 2,7. Dans le groupe temoin, tous les porcs sont decedes rapidement par stase splanchnique aigue. Conclusion - L'anastomose mesenterico-cave terminalisee a permis la tolerance hemodynamique et l'hypertrophie d'un transplant hepatique de moins de 30 % du poids ideal.

Performing an ex vivo liver perfusion as a transient liver support requires perfusing the liver with a flow of 1 ml/min-1 per kg-1 of liver, which could reach 25% of the cardiac output when a human liver is used. This high flow could be detrimental in patients with acute liver failure. Therefore, in an ischemic-induced liver failure pig model, we developed a circuit allowing low flows going out of and into the systemic circulation, whereas the flow going through the ex vivo liver is maintained at a high value. This was obtained by uncoupling the ex vivo circuit from the systemic circulation. Ex vivo liver perfusion was performed in a closed circuit with a flow averaging 1 ml/min-1 per kg-1 of ex vivo liver (700 to 800 ml/min-1, according to the weight of the livers we used). It was linked to the systemic circulation with input and output flows equal to that used during hemodialysis (200 ml/min-1). Compared with previously reported direct circuits, this perfusion system was well tolerated from a circulatory point of view. After the induction of ischemic liver failure, the ex vivo liver perfusion led to an increase in urea, branched amino acids to aromatic amino acid ratio, and fractional clearance of indocyanine green and galactose and to a decrease in ammonia and lactic acid. This system allowed the ex vivo liver to keep its clearing properties despite a low extracorporeal flow. It represents an extracorporeal circuit that could be used in place of the direct extracorporeal high-flow liver perfusion.

Background. A surgical technique using a mesocaval shunt and downstream ligation of the superior mesenteric vein has been recently proposed to overcome the size limitations that restrict the use of partial liver grafts. We designed an experimental study in pigs to evaluate the capacities of liver regeneration and hemodynamic changes after completion of this procedure.Material and methods. Liver regeneration after left hepatectomy was compared between two groups of five pigs, with or without mesocaval shunt, sacrificed 11 to 14 days after surgery. A third group of five animals was used for hemodynamic studies.Results. Liver regeneration in study animals was 45.3% of controls. This was obtained despite a reduction of the venous inflow to 15.6% of the control, resulting in a net decrease of the total blood inflow to 56% of the control, despite a compensatory increase in the arterial inflow. There was no significant difference in mitotic index, hepatocellular size, and glycogen content between study and control animals.Conclusion. Our experimental study confirms that the regenerative capacities of the pig liver are largely preserved despite the dramatic reduction of the venous blood inflow, reduced to its gastroduodenosplenopancreatic component. This lends further support to the hypothesis that the gastroduodenosplenopancreatic blood is enriched in hepatotrophic factors, likely to originate from the pancreas and duodenum. (c) 2007 Elsevier Inc. All rights reserved.

The goal of this study is to establish the effect of cadaveric liver retrieval, using the technique of aortic perfusion only, on liver graft function, and to identify associated potential risk factors for graft dysfunction. The authors reviewed the outcome of 400 consecutive, orthotopic, cadaveric liver transplantation retrieved by the technique of aortic perfusion only. Relevant parameters pertaining to the donor, recipient, procurement, graft and peri-operative variables are analyzed to assess their influence on graft function. The univariant analysis revealed that donor age, body mass index, blood pressure, and vasopressor dependence influence graft function. Furthermore, predictors of dysfunction included prolonged anhepatic phase, transplantation duration and partial grafts. In addition, multivariant analysis revealed significant association between obesity of donors, partial graft, and dysfunction. The technique of aortic perfusion only, is a simple and reproducible procedure. The post-transplantation outcomes appear to be similar to those reported for the traditional liver procurement technique.

The shortage of livers for transplant has renewed interest in the potential of temporary liver support such as extra corporeal whole liver perfusion. In an ischemic induced liver failure model we perfused an extra corporeal liver through only a portal vein and assessed the function of this ex vivo liver by using hepatic tests to estimate elimination as well as synthesis capacities. Acute liver failure was performed in five control pigs by a hepatic devascularization associated to an end to side portocaval shunt. In a treated group, 5 to 6 h after this hepatic devascularization, animals were connected to an extra corporeal liver perfused via the portal vein with blood withdrawn from the ischemic liver animal from its portal vein. Devascularization of the liver induced an increase in liver enzymes and ammonia, a drop in the ratio of branched chain amino acids to aromatic amino acids, and a decrease in blood urea and indocyanine green and galactose clearances. In treated animals, urea, amino acid ratio, and clearances increased after the ex vivo liver perfusion. In this group, mean bile production and mean liver oxygen consumption were 13.7 +/- 3.6 ml/h and 16.1 +/- 7.7 ml/min, respectively. In an acute ischemic liver failure pig model, an extra corporeal whole liver perfusion demonstrated detoxification properties as well as synthesis capacities.

This study reviews the evaluation and results of a new liver transplantation technique for small-for-size grafts with portomesenteric disconnection. Twenty Large-White pigs underwent heterotopic liver transplantation after a mesocaval shunt, ligation of the superior mesenteric vein downstream from the shunt, and ligation of the recipient portal vein near the native liver. The donor-to-recipient weight ratio was 24%, and the graft-to-recipient weight ratio was 0.6%. In five control pigs, no mesocaval shunt was performed. The mesocaval shunt provided diversion of 60% of the splanchnic blood flow. The median survival of study pigs was 39 days (range, 8 to 98). Median serum bilirubin levels at 1 week were 12 micromol/L (range, 4 to 59). At autopsy, graft weight was increased to 2.7 times the initial weight and histologic findings were normal. In the control group, all pigs died quickly of acute splanchnic congestion. Portomesenteric disconnection was effective to achieve survival of small-for-size grafts in pig liver transplantation.

We report a new technique of adult liver transplantation using a small-for-size graft. In order to avoid graft congestion and failure by overperfusion, we completely diverted the superior mesenteric venous flow by a mesocaval shunt with downstream ligation of the superior mesenteric vein. The recipient recovered well, and the graft had normal histology and function at 5 months follow-up. Given the current scarcity of cadaveric donors, this technique may increase the numbers of adult recipients by using left lobes from cadaveric split liver grafts.

BACKGROUND AND OBJECTIVE:Evaluation of a new pig liver transplantation technique for survival and hypertrophy of a small-sized graft by providing adapted and controlled venous portal flow.MATERIAL AND METHODS:[corrected] Twenty Large-White pigs underwent heterotopic liver transplantation after a mesocaval shunt and ligation of the superior mesenteric vein downstream from the shunt. The donor-to-recipient weight ratio was below 30%. Furthermore, recipient's biliary duct and portal vein into the hilum were tied. In a control group, no mesocaval shunt was performed and the graft received the entire splanchnic venous flow.RESULTS:The mesocaval shunt provided diversion of 60% of the splanchnic blood flow. The median survival of study pigs was 39 days (range: 8-98). Median serum bilirubin levels at 1 week were 12 micromol/L (range: 4-59). At autopsy, graft weight was increased to 2.7 times the initial weight and histological findings were normal. In the control group, all pigs died quickly from acute splanchnic congestion.CONCLUSION:In a model of heterotopic liver transplantation using small-sized grafts, complete diversion of mesenteric blood flow through a mesocaval shunt resulted in hemodynamic tolerance and hypertrophy of a graft corresponding to less than 30% of the ideal mass.

BACKGROUND:The order of revascularization in human liver grafts is still discussed. This study tries to answer this question in terms of hemodynamic data. STUDY DESIGN:Fifty-nine patients were randomized in this study to compare hemodynamic data just before and 15 minutes after revascularization of liver grafts in relation to first hepatic artery (n = 29) or first portal vein (n = 30) revascularization procedure. RESULTS:Hemodynamic variations were significantly greater in the portal vein group than in the hepatic artery group in terms of mean arterial pressure, cardiac index, central venous pressure, pulmonary capillary pressure, and systemic vascular resistance. The latter decreased from 741.8 +/- 390.3 to 659.9 +/- 411.1 dynes/ cm5 (NS) in the hepatic artery group versus 807.7 +/-336.7 to 439.7 +/- 215 dynes/cm5 (p < 0.05) in the portal vein group. Clinical results and postoperative complications, graft characteristics, patient survival, and graft survival were not significantly different between the groups. CONCLUSIONS:Initial arterial revascularization of the liver graft leads to a more stable hemodynamic profile during revascularization of the liver graft after vascular unclamping. This technique is always feasible and has become our reference procedure.

The development of hepatic encephalopathy, jaundice and coagulopathy defines acute liver failure (ALF). Both acute and chronic liver failure are associated with high morbidity and mortality. Orthotopic liver transplantation remains the only definitive treatment for patients but organ availability is a limiting factor. The rate of deterioration in case of ALF can be spectacularly abrupt and timing is crucial. The need of a temporary liver support system has been long accepted but has not yet been achieved. Over the past decades, alternative methods have been proposed to provide extra-corporeal hepatic support.

In children, living donor liver transplantation has been shown to be efficient in treating end-stage liver diseases when the left lateral segment is harvested. In adults, more liver mass is needed to provide adequate hepatic function. The aim of this study is to report 2 successful cases of living donor liver transplantation using a right hepatic lobe from adult.In 2 sons, the right hepatic lobe was harvested without the middle hepatic vein for transplantation in their fathers who were suffering from end-stage liver cirrhosis. Hepatectomy was done without vascular inflow occlusion after dissection of vascular and biliary structures, itself strictly restricted to the right side. In recipients, the graft was implanted orthotopically with preservation of the native inferior vena cava and after temporary porto-caval shunt.The duration of donors procedures was 7 h and 11 h 45 min; intra-operative transfusions comprised of 700 mL from cell-saver in the first case, and 1300 mL plus 1 autologous red blood cell unit in the second case. Graft weights were 770 g and 1100 g. None of the donors experienced liver failure and both were able to leave the hospital 9 days after the operation. In recipients, initial graft function was excellent in the first case and correct in the second case, despite the necessity to redo intra-operatively the hepatic vein anastomosis secondary to a twisting. Patients were discharged 20 and 40 days respectively following transplantation.Adult living donor liver transplantation using a right hepatic lobe is efficient and safe. This option could contribute to reducing the mortality of patients on the waiting list.

Background & Aims: Hepatic involvement in hereditary hemorrhagic telangiectasia is common but often asymptomatic. However, in some cases, the vascular lesions that involve the liver may lead to high-output cardiac failure and pulmonary hypertension that is predominant over hepatobiliary manifestations. Liver transplantation and treatment of these complications are described and discussed in this article. Methods: Three patients with hereditary hemorrhagic telangiectasia and hepatic involvement received transplants. They had pulmonary hypertension and chronic right-sided heart failure caused by disseminated intrahepatic telangiectasias with shunts between the hepatic artery and hepatic veins or portal vein. Left-to-right intrahepatic shunt output was estimated to range between 51% and 57.5% of cardiac output. Results: Hyperdynamic circulation disappeared after liver transplantation in all patients. Results of computed tomography and right-sided heart catheterization performed 6 months later were normal. Follow-up periods currently are 65, 53, and 29 months, and each patient continues to be asymptomatic. Conclusions: This report suggests that liver transplantation can be considered as an alternative and successful curative treatment that may prevent the irreversible evolution of cardiopulmonary disease.

STUDY AIM:In children, living donor liver transplantation has been shown to be efficient in treating end-stage liver diseases when the left lateral segment is harvested. In adults, more liver mass is needed to provide adequate hepatic function. The aim of this study is to report 2 successful cases of living donor liver transplantation using a right hepatic lobe from adult.PATIENTS AND METHODS:In 2 sons, the right hepatic lobe was harvested without the middle hepatic vein for transplantation in their fathers who were suffering from end-stage liver cirrhosis. Hepatectomy was done without vascular inflow occlusion after dissection of vascular and biliary structures, itself strictly restricted to the right side. In recipients, the graft was implanted orthotopically with preservation of the native inferior vena cava and after temporary porto-caval shunt.RESULTS:The duration of donors procedures was 7 h and 11 h 45 min; intra-operative transfusions comprised of 700 mL from cell-saver in the first case, and 1300 mL plus 1 autologous red blood cell unit in the second case. Graft weights were 770 g and 1100 g. None of the donors experienced liver failure and both were able to leave the hospital 9 days after the operation. In recipients, initial graft function was excellent in the first case and correct in the second case, despite the necessity to redo intra-operatively the hepatic vein anastomosis secondary to a twisting. Patients were discharged 20 and 40 days respectively following transplantation.CONCLUSION:Adult living donor liver transplantation using a right hepatic lobe is efficient and safe. This option could contribute to reducing the mortality of patients on the waiting list.

BACKGROUND:In this pilot study, we present the results of treatment of early (3 months after liver transplantation) acute rejection episodes by increasing only the tacrolimus doses.METHODS:Ten patients who received tacrolimus as primary treatment experienced acute mild (one case), moderate (four cases), or severe (five cases) rejection episodes. Tacrolimus dosing was increased 1-2 mg every 1 or 2 days until hepatic enzymes started to improve. Steroid basic daily doses were kept unchanged.RESULTS:With the daily dose of tacrolimus increased by a median 1.89-fold (range: 1.2-5), alanine aminotransferase, bilirubin, and gamma-glutamyltranspeptidase levels rapidly reached normal values within the first month. During a median follow-up time of 19.5 months (range: 14-24), none of the 10 patients died or lost their graft. Control liver biopsies were done 13.5 months (range: 7-19) after rejection episode in all patients, and none demonstrated evidence of rejection or sequela.CONCLUSION:This pilot study suggests that increasing tacrolimus dosage could be considered as treatment against early acute rejection episodes including the severe grade.

Nous rapportons notre experience de la deconnexion azygo-portale pour rupture de varices oesophagiennes dans le cadre de thrombose portale diffuse extra-hepatique sur foie sain chez 7 patients adultes. La transsection oesophagienne a ete effectuee par agrafage circulaire. Les recidives sont frequentes, mais tous les patients sont en vie avec un recul moyen de 73 mois. La chirurgie a ete proposee apres echec de la sclerotherapie. Les shunts mesenterico-caves et spleno-renaux distaux n'ont pu etre utilises du fait de la thrombose de la veine mesenterique et splenique chez tous les patients.

Le but de ce travail etait de mettre au point un modele de perfusion ex vivo physiologique par double voie arterielle et porte de foie ex situ. Les prelevements etaient faits sur des porcs Landrace de 20-25 kg sous anesthesie generale. Quatre groupes (G1a, G1b, G2 et G3) etaient etudies en fonction de la modalite d'oxygenation et de la solution de rincage hepatique: l'oxygenation etait realisee soit par un melange de O 2 95 % + CO 2 5 % dans le G1a (n = 5), soit par un melange d'azote 76 % + O 2 19 % + CO 2 5 % dans les autres groupes. Le rincage hepatique etait fait par du Ringer lactate dans les G1a et G1b (n = 5), de l'Elohes dans le G2 (n = 6) ou par la solution UW dans le G3 (n = 6). Les perfusions etaient realisees par du sang autologue ou homologue total heparine. Le debit total de perfusion etait de 1 ml/g de foie/min dont 25 % par voie arterielle et 75 % par voie porte. Resultats : l'equilibre hemodynamique, entre l'entree du sang dans le foie par double voie arterio-porte et sa sortie par la canule cave, etait assure grâce a une pression de perfusion porte de 15 + 4,3 cm H 2 O. Dans le G1a, l'apparition de lesions hepatocytaires irreversibles avec production de bile tres pauvre en bilirubine totale etait attribuee a la valeur trop elevee de la PO 2 et a une PCO 2 effondree. Une gazometrie normale etait assuree dans les autres groupes avec la production de bile a forte concentration en bilirubine totale. Le bilan hepatique montrait une elevation des transaminases dans tous les groupes sauf le G3, et une hyperglycemie qui etait plus moderee dans le G3. Seul le G3 avait un TP normal, un Facteur V le plus eleve en fin de perfusion et un taux normal de lactate. L'etude histologique en microscopie optique a montre dans le G3 la preservation de l'architecture hepatocytaire. Conclusion: ces resultats soulignent l'importance des modalites d'oxygenation dans les perfusions de foie ex vivo. Un fonctionnement optimal de perfusion ex vivo de foie ex situ etait obtenu dans le G3 grâce aux conditions optimales de conservation, d'oxygenation et d'une hemodynamique physiologique. Les alterations biologiques et histologiques etaient comparables dans les G1a, G1b et G2, seule la chronologie de leur survenue etait differente.