Antoni Rimola

Consorci Institut D'Investigacions Biomediques August Pi I Sunyer

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Miquel Navasa

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas

Joan Rodés

Consorci Institut D'Investigacions Biomediques August Pi I Sunyer

Vicente Arroyo

European Foundation for the Study of Chronic Liver Failure

Juan Carlos García‐Valdecasas

Hospital Clínic de Barcelona

Pere Ginès

Consorci Institut D'Investigacions Biomediques August Pi I Sunyer

Luís Grande

Hospital Del Mar

Joan Roselló‐Catafau

Institut d'Investigacions Biomèdiques de Barcelona

Alberto Sánchez‐Fueyo

King's College London

J Rodés

Hospital Clínic de Barcelona

Josep Fuster

Universitat de Barcelona

Cooperative Institutions

Universitat de Barcelona

412

Hospital Clínic de Barcelona

324

Consorci Institut D'Investigacions Biomediques August Pi I Sunyer

302

Inserm

275

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas

209

Instituto de Salud Carlos III

200

Centro de Investigación Biomédica en Red

192

Istituti di Ricovero e Cura a Carattere Scientifico

178

University College London

162

Centre National de la Recherche Scientifique

146

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Predictive factors of early postoperative graft function in human liver transplantation

Hepatology (1994)

Xavier González-Argenté Antoni Rimola Luís Grande Maria Antolı́n Juan Carlos García‐Valdecasas

To identify factors predictive of early postoperative graft function, we analyzed 54 variables—including easily available clinical and laboratory data prospectively obtained from organ donors, transplant recipients and surgical procedures in 168 consecutive liver transplantations. Early postoperative graft function was classified into three groups according to a scoring system ranging from 3 to 9 based on peak serum ALT values, mean bile output and lowest prothrombin activity measured during the 72 hr after transplant: group 1 (score 3 to 4, good graft function; n = 73), group 2 (score 5 to 6, moderate dysfunction; n = 50) and group 3 (score, 7 to 9, severe dysfunction; n = 45). In univariate analyses, 8 of the 54 variables analyzed were statistically significant (p < 0.05) predictors of severe graft dysfunction: high serum sodium concentration and brain death caused by cranial trauma in organ donors, advanced age and low prothrombin activity in transplant recipients, prolonged total ischemia time and large transfusions of red blood cells, fresh frozen plasma and platelets during surgery. After introduction of these eight variables in a multivariate analysis, only four were found to independently predict early postoperative graft function: donor serum sodium concentration, total ischemia time, platelet transfusion during surgery and recipient prothrombin activity. In 52 liver transplantations, in which the predictive value of liver tissue adenine nucleotide concentration and several biochemical sensitive markers of donor nutritional status was also analyzed, only the ATP level in liver tissue obtained at the time of organ reperfusion was identified as an independent predictor of initial graft function. We conclude that the degree of early postoperative graft dysfunction in liver transplantation can be predicted on the basis of data from organ donors, transplant recipients and surgical events. (Hepatology 1994;20:565-573).

10.1002/hep.1840200304

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Citations (262)

Hepatopulmonary syndrome in candidates for liver transplantation

Journal of Hepatology (2001)

G.P Martı́nez Joan Albert Barberà Josep Visa Antoni Rimola J. C. Paré

Hepatopulmonary syndrome

DLCO

10.1016/s0168-8278(00)00108-2

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Citations (208)

Intra-graft expression of genes involved in iron homeostasis predicts the development of operational tolerance in human liver transplantation

Journal of Clinical Investigation (2011)

Felix Bohne Marc Martínez‐Llordella Juan José Lozano Rosa Miquel Carlos Benítez

Following organ transplantation, lifelong immunosuppressive therapy is required to prevent the host immune system from destroying the allograft. This can cause severe side effects and increased recipient morbidity and mortality. Complete cessation of immunosuppressive drugs has been successfully accomplished in selected transplant recipients, providing proof of principle that operational allograft tolerance is attainable in clinical transplantation. The intra-graft molecular pathways associated with successful drug withdrawal, however, are not well defined. In this study, we analyzed sequential blood and liver tissue samples collected from liver transplant recipients enrolled in a prospective multicenter immunosuppressive drug withdrawal clinical trial. Before initiation of drug withdrawal, operationally tolerant and non-tolerant recipients differed in the intra-graft expression of genes involved in the regulation of iron homeostasis. Furthermore, as compared with non-tolerant recipients, operationally tolerant patients exhibited higher serum levels of hepcidin and ferritin and increased hepatocyte iron deposition. Finally, liver tissue gene expression measurements accurately predicted the outcome of immunosuppressive withdrawal in an independent set of patients. These results point to a critical role for iron metabolism in the regulation of intra-graft alloimmune responses in humans and provide a set of biomarkers to conduct drug-weaning trials in liver transplantation.

Immunosuppression

Immunosuppressive drug

Drug withdrawal

Homeostasis

10.1172/jci59411

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Citations (197)

Superior Preservation of DCD Livers With Continuous Normothermic Perfusion

Annals of Surgery (2011)

Constantino Fondevila Amelia J. Hessheimer Mark-Hugo J. Maathuis Javier Muñoz Pilar Taurá

Unexpected donation after cardiac death (DCD) donors suffer cardiac arrest suddenly and are maintained with normothermic extracorporeal membrane oxygenation (NECMO) while consent for donation is obtained. The objective of this study was to determine whether ex vivo normothermic machine perfusion (NMP) improves upon the benefits of NECMO in a large-animal model of unexpected DCD liver transplant.Donor pigs underwent 90-minute cardiac arrest and were divided in to 3 groups. In the first, livers were preserved immediately with cold storage (CS, n = 6). In the other 2 groups, donors underwent 60-minute NECMO followed by CS (NECMO+CS, n = 6) or NMP (NECMO+NMP, n = 6). After 4-hour preservation, livers were transplanted into recipient pigs.Five-day survival was 0 in CS, 83% in NECMO+CS, and 100% in NECMO+NMP. After reperfusion, injury, and inflammatory markers rose significantly among CS grafts, all of which developed primary nonfunction. Sixty minutes of NECMO, however, resulted in only 1 death, whereas NECMO followed by NMP led to no deaths and significant improvements in injury, inflammation, and synthetic function in comparison to NECMO and CS.Although 60 minutes recuperative NECMO is better than CS alone, NMP improves further on NECMO and may have a role in preserving DCD livers in the clinical setting.

10.1097/sla.0b013e31822b8b2f

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Citations (176)

Steroids and Living Liver Donation Increase Tacrolimus Blood Levels in Living Donor Liver Transplantation

Transplantation Proceedings (2005)

R. Charco Antoni Rimola Juan Carlos García‐Valdecasas Josep Fuster Constantino Fondevila

Trough level

Immunosuppression

Trough Concentration

Cadaveric spasm

10.1016/j.transproceed.2005.10.082

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Citations (8)

Contents, Vol. 42, 1986

The Nephron journals/Nephron journals (1986)

Jürgen Merke Eberhard Ritz Ricardo Boland E. Heidbreder R. Götz

10.1159/000183687

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Citations (0)

Liver transplantation in patients with non-biliary cirrhosis

European Journal of Gastroenterology & Hepatology (1998)

Eleazar González Antoni Rimola Miquel Navasa Hernán Andreu Luís Grande

González, Eleazar; Rimola, Antoni; Navasa, Miquel; Andreu, Hernan; Grande, Luis; Garcia-Valdecasas, Juan-Carlos; Cirera, Isabel; Visa, Josep; Rodes, Juan

10.1097/00042737-199803000-00018

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Polyethylene glycol rinse solution: An effective way to prevent ischemia-reperfusion injury

World Journal of Gastroenterology (2014)

Mohamed Amine Zaoualí Mohamed Béjaoui Marı́a Calvo Emma Folch‐Puy Eirini Pantazi

AIM:To test whether a new rinse solution containing polyethylene glycol 35 (PEG-35) could prevent isch-emia-reperfusion injury (IRI) in liver grafts. METHODS:Sprague-Dawley rat livers were stored in University of Wisconsin preservation solution and then washed with different rinse solutions (Ringer's lactate solution and a new rinse solution enriched with PEG-35 at either 1 or 5 g/L) before ex vivo perfusion with Krebs-Heinseleit buffer solution.We assessed the following: liver injury (transaminase levels), mitochondrial damage (glutamate dehydrogenase activity), liver function (bile output and vascular resistance), oxidative stress (malondialdehyde), nitric oxide, liver autophagy (Beclin-1 and LCB3) and cytoskeleton integrity (filament and globular actin fraction); as well as levels of metalloproteinases (MMP2 and MMP9), adenosine monophosphate-activated protein kinase (AMPK), heat shock protein 70 (HSP70) and heme oxygenase 1 (HO-1). RESULTS:When we used the PEG-35 rinse solution, reduced hepatic injury and improved liver function were noted after reperfusion.The PEG-35 rinse solution prevented oxidative stress, mitochondrial damage, and liver autophagy.Further, it increased the expression of cytoprotective heat shock proteins such as HO-1 and HSP70, activated AMPK, and contributed to the restoration of cytoskeleton integrity after IRI. CONCLUSION:Using the rinse solution containing PEG-35 was effective for decreasing liver graft vulnerability to IRI.

10.3748/wjg.v20.i43.16203

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Citations (31)

A prospective randomized open study in liver transplant recipients: Daclizumab, mycophenolate mofetil, and tacrolimus versus tacrolimus and steroids

Liver Transplantation (2009)

Alejandra Otero Evaristo Varó J. Ortiz de Urbina R Martín-Vivaldi Valentín Cuervas‐Mons

This open-label, randomized study compared the efficacy of a regimen of corticosteroids and tacrolimus (standard therapy group, n = 79) with a regimen of daclizumab induction therapy in combination with mycophenolate mofetil and tacrolimus (modified therapy group, n = 78) in primary liver transplant recipients. The primary endpoint was biopsy-proven acute rejection (BPAR) at 24 weeks. Secondary endpoints included time to rejection and patient and graft survival. The incidence of BPAR was significantly reduced in the modified therapy group compared to the standard therapy group (11.5% versus 26.6%, respectively, P = 0.017). The time to rejection was significantly shorter in the standard therapy group compared with the modified therapy group (P = 0.044). There was no significant difference between groups in patient or graft survival. Hepatitis C virus–positive patients exhibited no differences from hepatitis C virus–negative patients with respect to the incidence of BPAR. A steroid-sparing regimen of daclizumab, mycophenolate mofetil, and tacrolimus was effective and well tolerated in the prevention of BPAR in adult liver transplant recipients in comparison with a standard regimen of tacrolimus and steroids. Liver Transpl 15:1542–1552, 2009. © 2009 AASLD.

Daclizumab

Regimen

Mycophenolate

10.1002/lt.21854

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Citations (34)

Optimization of liver grafts in liver retransplantation: A European single-center experience

Surgery (2008)

Josep Martí R. Charco Joana Ferrer David G. Calatayud Antoni Rimola

Single Center

Center (category theory)

10.1016/j.surg.2008.06.029

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Citations (39)