96 results on '"Clavien, Pierre A."'
Search Results
2. Defining MoRAL After Liver Transplantation.
- Author
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Clavien PA, Dutkowski P, and Lillemoe KD
- Subjects
- Disease-Free Survival, Humans, Risk Assessment, Treatment Outcome, Carcinoma, Hepatocellular surgery, Decision Support Techniques, Health Status Indicators, Liver Neoplasms surgery, Liver Transplantation
- Published
- 2017
- Full Text
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3. Scorecard and insights from approaches to liver allocation around the world.
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Dutkowski P and Clavien PA
- Subjects
- Health Care Rationing, Humans, Tissue and Organ Procurement, Liver Transplantation
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- 2016
- Full Text
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4. Are there better guidelines for allocation in liver transplantation? A novel score targeting justice and utility in the model for end-stage liver disease era.
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Dutkowski P, Oberkofler CE, Slankamenac K, Puhan MA, Schadde E, Müllhaupt B, Geier A, and Clavien PA
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- Adult, Cold Ischemia, Female, Guidelines as Topic, Humans, Logistic Models, Male, Middle Aged, Risk Assessment, United States, Waiting Lists, End Stage Liver Disease surgery, Health Care Rationing standards, Liver Transplantation mortality, Resource Allocation standards, Severity of Illness Index, Tissue and Organ Procurement standards
- Abstract
Objectives: To design a new score on risk assessment for orthotopic liver transplantation (OLT) based on both donor and recipient parameters., Background: The balance of waiting list mortality and posttransplant outcome remains a difficult task in the era of the model for end-stage liver disease (MELD)., Methods: Using the United Network for Organ Sharing database, a risk analysis was performed in adult recipients of OLT in the United States of America between 2002 and 2010 (n = 37,255). Living donor-, partial-, or combined-, and donation after cardiac death liver transplants were excluded. Next, a risk score was calculated (balance of risk score, BAR score) on the basis of logistic regression factors, and validated using our own OLT database (n = 233). Finally, the new score was compared with other prediction systems including donor risk index, survival outcome following liver transplantation, donor-age combined with MELD, and MELD score alone., Results: Six strongest predictors of posttransplant survival were identified: recipient MELD score, cold ischemia time, recipient age, donor age, previous OLT, and life support dependence prior to transplant. The new balance of risk score stratified recipients best in terms of patient survival in the United Network for Organ Sharing data, as in our European population., Conclusions: The BAR system provides a new, simple and reliable tool to detect unfavorable combinations of donor and recipient factors, and is readily available before decision making of accepting or not an organ for a specific recipient. This score may offer great potential for better justice and utility, as it revealed to be superior to recent developed other prediction scores.
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- 2011
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5. Liver graft protection by antiapoptotic drugs: a step further.
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Georgiev P, Clavien PA, and Gores GJ
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- Animals, Caspase Inhibitors, Graft Rejection pathology, Humans, Liver Transplantation pathology, Organ Preservation methods, Organ Preservation Solutions pharmacology, Rats, Reperfusion Injury pathology, Reperfusion Injury prevention & control, Temperature, Treatment Outcome, Apoptosis drug effects, Enzyme Inhibitors pharmacology, Graft Rejection prevention & control, Liver Transplantation methods, Pentanoic Acids pharmacology
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- 2007
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6. Bile salt toxicity aggravates cold ischemic injury of bile ducts after liver transplantation in Mdr2+/- mice.
- Author
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Hoekstra H, Porte RJ, Tian Y, Jochum W, Stieger B, Moritz W, Slooff MJ, Graf R, and Clavien PA
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- ATP Binding Cassette Transporter, Subfamily B genetics, Animals, Bile Duct Diseases pathology, Bile Ducts pathology, Mice, Severity of Illness Index, ATP-Binding Cassette Sub-Family B Member 4, ATP Binding Cassette Transporter, Subfamily B physiology, Bile Acids and Salts physiology, Bile Duct Diseases etiology, Bile Ducts blood supply, Cold Ischemia adverse effects, Liver Transplantation adverse effects
- Abstract
Intrahepatic bile duct strictures are a serious complication after orthotopic liver transplantation (OLT). We examined the role of endogenous bile salt toxicity in the pathogenesis of bile duct injury after OLT. Livers from wild-type mice and mice heterozygous for disruption of the multidrug resistance 2 Mdr2 gene (Mdr2+/-) were transplanted into wild-type recipient mice. Mdr2+/- mice secrete only 50% of the normal amount of phospholipids into their bile, leading to an abnormally high bile salt/phospholipid ratio. In contrast to homozygous Mdr2-/- mice, the Mdr2+/- mice have normal liver histology and function under normal conditions. Two weeks after OLT, bile duct injury and cholestasis were assessed by light and electron microscopy, as well as through molecular and biochemical markers. There were no signs of bile duct injury or intrahepatic cholestasis in liver grafts from wild-type donors. Liver grafts from Mdr2+/- donors, however, had enlarged portal tracts with cellular damage, ductular proliferation, biliostasis, and a dense inflammatory infiltrate after OLT. Parallel to this observation, recipients of Mdr2+/- livers had significantly higher serum transaminases, alkaline phosphatase, total bilirubin, and bile salt levels, as compared with recipients of wild-type livers. In addition, hepatic bile transporter expression was compatible with the biochemical and histological cholestatic profile found in Mdr2+/- grafts after OLT. In conclusion, toxic bile composition, due to a high biliary bile salt/phospholipid ratio, acted synergistically with cold ischemia in the pathogenesis of bile duct injury after transplantation.
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- 2006
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7. Mycophenolate mofetil for renal dysfunction in liver transplant recipients on cyclosporine or tacrolimus: randomized, prospective, multicenter pilot study results.
- Author
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Reich DJ, Clavien PA, and Hodge EE
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- Adult, Aged, Cyclosporine administration & dosage, Cyclosporine therapeutic use, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug Therapy, Combination, Female, Glomerular Filtration Rate, Humans, Immunosuppressive Agents therapeutic use, Male, Middle Aged, Mycophenolic Acid administration & dosage, Mycophenolic Acid therapeutic use, Pilot Projects, Tacrolimus administration & dosage, Treatment Outcome, Liver Transplantation immunology, Mycophenolic Acid analogs & derivatives, Tacrolimus therapeutic use
- Abstract
Background: Liver transplantation (LTX) recipients with renal dysfunction may benefit from mycophenolate mofetil (MMF) and reduction or discontinuation of nephrotoxic calcineurin inhibitors (CNI). The authors report the first randomized, multicenter pilot studies of this approach (one study for patients on cyclosporine [CsA] and one for those on tacrolimus [Tac])., Methods: Patients 3 to 27 months post-LTX with greater than 20% reduced renal function since LTX, and creatinine 1.8 to 4.0 mg/dL, creatinine clearance 20 to 60 mL/min, or both, were randomized to discontinuation (group 1) or 50% reduction (group 2) of CNI dose, together with MMF 1.5 g administered twice daily and prednisone. Endpoints included measured glomerular filtration rate (GFR) 52 weeks after study entry and biopsy-proven rejection., Results: In the CsA and Tac trials, 15 and 12 patients, respectively, completed the 52-week follow-up. In the CsA trial, the mean GFR at baseline and week 52 were 35.0 and 57.8 mL/min (>15% improvement, five of six; unchanged, one of six) for group 1 and 46.0 and 63.8 mL/min (>15% improvement, four of nine; unchanged, three of nine; >15% deterioration, two of nine) for group 2. In the Tac trial, GFRs were 55.4 and 56.0 mL/min (>15% improvement, two of five; unchanged, three of five) for group 1 and 46.7 and 60.2 mL/min (>15% improvement, four of seven; unchanged, three of seven) for group 2. Mild or moderate rejection occurred in 38% and 9% of patients in groups 1 and 2 of the CsA trial and in 14% of each group of the patients in the Tac trial., Conclusions: These pilot studies show that in LTX recipients with renal dysfunction, MMF allows CNI dose reduction or discontinuation, improving or stabilizing GFR in most patients.
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- 2005
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8. Cost-effectiveness of cadaveric and living-donor liver transplantation.
- Author
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Sagmeister M, Mullhaupt B, Kadry Z, Kullak-Ublick GA, Clavien PA, and Renner EL
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- Adult, Aged, Cadaver, Cost-Benefit Analysis, Graft Survival, Humans, Liver Transplantation mortality, Liver Transplantation physiology, Middle Aged, Survival Rate, Switzerland, Time Factors, Liver Transplantation economics, Living Donors, Tissue Donors, Tissue and Organ Procurement economics
- Abstract
Background: Cadaveric liver transplantation (5-year survival >80%) represents the standard of care for end-stage liver disease (ESLD). Because the demand for cadaveric organs exceeds their availability, living-donor liver transplantation has gained increasing acceptance. Our aim was to assess the marginal cost-effectiveness of cadaveric and living-donor orthotopic liver transplantation (OLT) in adults with ESLD., Methods: Using a Markov model, outcomes and costs of ESLD treated (1) conservatively, (2) with cadaveric OLT alone, and (3) with cadaveric OLT or living-donor OLT were computed. The model was validated with published data. The case-based scenario consisted of data on all 15 ESLD patients currently on our waiting list (3 women, 12 men; median age, 48 years [range, 33-59 years]) and on the outcome of all OLT performed for ESLD at our institution since 1995 (n=51; actuarial 5-year survival 93%). Living-donor OLT was allowed in 15% during the first year of listing; fulminant hepatic failure and hepatocellular carcinoma were excluded., Results: Cadaveric OLT gained on average 6.2 quality-adjusted life-years (QALYs) per patient compared with conservative treatment, living-donor OLT, an additional 1.3 QALYs compared with cadaveric OLT alone. Marginal cost-effectiveness of a program with cadaveric OLT alone and a program with cadaveric and living-donor OLT combined were similar (E 22,451 and E 23,530 per QALY gained). Results were sensitive to recipient age and postoperative survival rate., Conclusions: Offering living-donor OLT in addition to cadaveric OLT improves survival at costs comparable to accepted therapies in medicine. Cadaveric OLT and living-donor OLT are cost-effective.
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- 2002
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9. Low‐dose aspirin confers protection against acute cellular allograft rejection after primary liver transplantation
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Oberkofler, Christian E, Raptis, Dimitri A, Müller, Philip C, da Silva, Richard X Sousa, Lehmann, Kuno, Ito, Takahiro, Owen, Timothy, Pollok, Joerg‐Matthias, Parente, Alessandro, Schlegel, Andrea, Peralta, Peregrina, Winter, Erin, Selzner, Markus, Fodor, Margot, Maglione, Manuel, Jaklitsch, Manuel, Marques, Hugo P, Chavez‐Villa, Mariana, Contreras, Alan, Kron, Philipp, Lodge, Peter, Alford, Scott, Rana, Abbas, Magistri, Paolo, Di Benedetto, Fabrizio, Johnson, Bethany, Kirchner, Varvara, Bauldrick, Francis, Halazun, Karim J, Ghamarnedjad, Omid, Mehrabi, Arianeb, Basto, Samanta Teixeira, Fernandes, Eduardo SM, Paladini, Jose, de Santibañes, Martin, Florman, Sander, Tabrizian, Parissa, Dutkowski, Philipp, Clavien, Pierre‐Alain, Busuttil, Ronald W, Kaldas, Fady M, and Petrowsky, Henrik
- Subjects
Digestive Diseases ,Liver Disease ,Clinical Research ,Transplantation ,Organ Transplantation ,Prevention ,Adult ,Humans ,Liver Transplantation ,Cohort Studies ,Graft Rejection ,Thrombosis ,Allografts ,Graft Survival ,Retrospective Studies ,Risk Factors ,Clinical Sciences ,Surgery - Abstract
This study investigated the effect of low-dose aspirin in primary adult liver transplantation (LT) on acute cellular rejection (ACR) as well as arterial patency rates. The use of low-dose aspirin after LT is practiced by many transplant centers to minimize the risk of hepatic artery thrombosis (HAT), although solid recommendations do not exist. However, aspirin also possesses potent anti-inflammatory properties and might mitigate inflammatory processes after LT, such as rejection. Therefore, we hypothesized that the use of aspirin after LT has a protective effect against ACR. This is an international, multicenter cohort study of primary adult deceased donor LT. The study included 17 high-volume LT centers and covered the 3-year period from 2013 to 2015 to allow a minimum 5-year follow-up. In this cohort of 2365 patients, prophylactic antiplatelet therapy with low-dose aspirin was administered in 1436 recipients (61%). The 1-year rejection-free survival rate was 89% in the aspirin group versus 82% in the no-aspirin group (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.63-0.94; p = 0.01). The 1-year primary arterial patency rates were 99% in the aspirin group and 96% in the no-aspirin group with an HR of 0.23 (95% CI, 0.13-0.40; p
- Published
- 2022
10. Surgical Complications After Liver Transplantation (Vascular and Biliary)
- Author
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Tschuor, Christoph, Dutkowski, Philipp, Clavien, Pierre-Alain, and Burra, Patrizia, editor
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- 2022
- Full Text
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11. Transplantation of a human liver following 3 days of ex situ normothermic preservation
- Author
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Clavien, Pierre-Alain, Dutkowski, Philipp, Mueller, Matteo, Eshmuminov, Dilmurodjon, Bautista Borrego, Lucia, Weber, Achim, Muellhaupt, Beat, Sousa Da Silva, Richard X, Burg, Brian R, Rudolf von Rohr, Philipp, Schuler, Martin J, Becker, Dustin, Hefti, Max, Tibbitt, Mark W, University of Zurich, and Clavien, Pierre-Alain
- Subjects
1502 Bioengineering ,Biomedical Engineering ,2204 Biomedical Engineering ,610 Medicine & health ,Bioengineering ,Organ Preservation ,Applied Microbiology and Biotechnology ,Liver Transplantation ,Perfusion ,10219 Clinic for Gastroenterology and Hepatology ,Liver ,10049 Institute of Pathology and Molecular Pathology ,1313 Molecular Medicine ,1305 Biotechnology ,Quality of Life ,2402 Applied Microbiology and Biotechnology ,Humans ,Molecular Medicine ,Biotechnology - Abstract
Current organ preservation methods provide a narrow window (usually12 hours) to assess, transport and implant donor grafts for human transplantation. Here we report the transplantation of a human liver discarded by all centers, which could be preserved for several days using ex situ normothermic machine perfusion. The transplanted liver exhibited normal function, with minimal reperfusion injury and the need for only a minimal immunosuppressive regimen. The patient rapidly recovered a normal quality of life without any signs of liver damage, such as rejection or injury to the bile ducts, according to a 1-year follow up. This inaugural clinical success opens new horizons in clinical research and promises an extended time window of up to 10 days for assessment of viability of donor organs as well as converting an urgent and highly demanding surgery into an elective procedure.
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- 2022
12. Liver Transplantation for Hepatocellular Carcinoma
- Author
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Györi, Georg, Clavien, Pierre-Alain, Lesurtel, Mickaël, Markman, Maurie, Series editor, and Carr, Brian I., editor
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- 2016
- Full Text
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13. Defatting of Human Livers During Long-Term ex situ Normothermic Perfusion: Novel Strategy to Rescue Discarded Organs for Transplantation.
- Author
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Silva, Richard X. Sousa Da, Borrego, Lucia Bautista, Lenggenhager, Daniela, Huwyler, Florian, Binz, Jonas, Mancina, Leandro, Breuer, Eva, Wernlé, Kendra, Hefti, Max, Mueller, Matteo, Cunningham, Leslie, De Oliveira, Michelle L., Petrowsky, Henrik, Weber, Achim, Dutkowski, Philipp, Hoffmann, Waldemar, Gupta, Anurag, Tibbitt, Mark W., Humar, Bostjan, and Clavien, Pierre-Alain
- Abstract
Objective: To develop a protocol for the defatting of steatotic liver grafts during long-term ex situ normothermic machine perfusion. Background: Despite the alarming increase in donor organ shortage, the highly prevalent fatty liver grafts are often discarded due to the risk of primary nonfunction. Effective strategies preventing such outcomes are currently lacking. An exciting new avenue is the introduction of ex situ normothermic machine perfusion (NMP), enabling a liver to remain fully functional for up to 2 weeks and providing a unique window of opportunity for defatting before transplantation. Methods: Over a 5-year period, 23 discarded liver grafts and 28 partial livers from our resection program were tested during ex situ normothermic machine perfusion. The steatosis degree was determined on serial biopsies by expert pathologists, and triglyceride contents were measured simultaneously. Results: Of 51 liver grafts, 20 were steatotic, with up to 85%macrovesicular steatosis, and were perfused for up to 12 days. Ten livers displayed marked (5 of which almost complete) loss of fat, while the other 10 did not respond to long-term perfusion. Successful defatting was related to prolonged perfusion, automated glucose control, circadian nutrition, and L-carnitine/ fenofibrate supplementation. Pseudopeliotic steatosis and the associated activation of Kupffer/stellate cells were unexpected processes that might contribute to defatting. Synthetic and metabolic functions remained preserved for most grafts until perfusion ended. Conclusion: Ex situ long-term perfusion effectively reduces steatosis while preserving organ viability and may in the future allow transplantation of primarily unusable high-risk grafts, significantly increasing the number of organs available for transplantation. [ABSTRACT FROM AUTHOR]
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- 2023
- Full Text
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14. Calpain is a Mediator of Preservation-Reperfusion Injury in Rat Liver Transplantation
- Author
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Kohli, Vivek, Gao, Wenshi, Camargo, Carlos A., and Clavien, Pierre Alain
- Published
- 1997
15. A Spectrofluorometric Method for Real-Time Graft Assessment and Patient Monitoring
- Author
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Huwyler, Florian, Eden, Janina, Binz, Jonas, Cunningham, Leslie, Sousa Da Silva, Richard X., Clavien, Pierre-Alain, Dutkowski, Philipp, Tibbitt, Mark, and Hefti, Max
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liver transplantation ,translational research ,biomarkers ,biomedical engineering ,biosensors - Abstract
Biomarkers are powerful clinical diagnostics and predictors of patient outcome. However, robust measurements often require time and expensive laboratory equipment, which is insufficient to track rapid changes and limits direct use in the operating room. Here, this study presents a portable spectrophotometric device for continuous real-time measurements of fluorescent and non-fluorescent biomarkers at the point of care. This study measures the mitochondrial damage biomarker flavin mononucleotide (FMN) in 26 extended criteria human liver grafts undergoing hypothermic oxygenated perfusion to guide clinical graft assessment. Real-time data identified seven organs unsuitable for transplant that are discarded. The remaining grafts are transplanted and FMN values correlated with post-transplant indicators of liver function and patient recovery. Further, this study shows how this device can be used to monitor dialysis patients by measuring creatinine in real-time. Our approach provides a simple method to monitor biomarkers directly within biological fluids to improve organ assessment, patient care, and biomarker discovery., Advanced Science, ISSN:2198-3844
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- 2023
- Full Text
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16. Circulatory Injury in Liver Transplantation
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El-Badry, Ashraf Mohammad, Dutkowski, Philipp, Clavien, Pierre-Alain, DeLeve, Laurie D., editor, and Garcia-Tsao, Guadalupe, editor
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- 2011
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17. Introduction: Liver
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Clavien, Pierre-Alain, Fong, Yuman, CLAVIEN, PIERRE-ALAIN, editor, Sarr, Michael G., editor, Fong, Yuman, editor, and Miyazaki, Masaru, editor
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- 2016
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18. Kupffer Cell-Dependent TNF-α Signaling Mediates Injury in the Arterialized Small-for-Size Liver Transplantation in the Mouse
- Author
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Tian, Yinghua, Jochum, Wolfram, Georgiev, Panco, Moritz, Wolfgang, Graf, Rolf, and Clavien, Pierre-Alain
- Published
- 2006
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19. Recurrence of primary sclerosing cholangitis after liver transplantation: Analysing the European Liver Transplant Registry and beyond
- Author
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Visseren, Thijmen, Erler, Nicole Stephanie, Polak, Wojciech Grzegorz, Adam, René, Karam, Vincent, Vondran, Florian Wolfgang Rudolf, Ericzon, Bo‐Goran, Thorburn, Douglas, IJzermans, Jan Nicolaas Maria, Paul, Andreas, Heide, Frans, Taimr, Pavel, Nemec, Petr, Pirenne, Jacques, Romagnoli, Renato, Metselaar, Herold Johnny, Darwish Murad, Sarwa, Vondran, Florian, Bergquist, Annika, Lindström, Lina, Snowdon, Victoria, van der Heide, Frans, Trunecka, Pavel, Salizzoni, Mauro, Arendtsen Rostved, Andreas, Arenga, Giuseppe, Berlakovich, Gabriela A, Candinas, Daniel, Markovic, Sasa, Troisi, Roberto, van Hoek, Bart, Kanmaz, Turan, Dayangac, Murat, Berney, Thierry, Sforza, Daniele, Gridelli, Bruno, Clavien, Pierre‐Alain, Hoppe‐Lotichius, Maria, Senninger, Norbert, Lorf, Thomas, Settmacher, Utz, Cuervas‐Mons, Valentín, Bacakoğlu, Aylin, Nadalin, Silvio, Serra, Valentina, Pacholczyk, Marek, Baccarani, Umberto, Dopazo Taboada, Cristina, Berenguer, Marina, San Juan, Fernando, Detry, Olivier, Stippel, Dirk, Evrard, Philippe, Gugenheim, Jean, Kiliç, Murat, Fernández Selles, Carlos, Norena, Luis Antonio Herrera, Melandro, Fabio, Gonzalez‐Pinto, Ignacio, Nicolini, Daniele, Pardo Sánchez, Fernando, Neumann‐Haefelin, Christoph, Gastroenterology & Hepatology, Surgery, Epidemiology, Visseren, T., Erler, N. S., Polak, W. G., Adam, R., Karam, V., Vondran, F. W. R., Ericzon, B. -G., Thorburn, D., Ijzermans, J. N. M., Paul, A., van der Heide, F., Taimr, P., Nemec, P., Pirenne, J., Romagnoli, R., Metselaar, H. J., Darwish Murad, S., Vondran, F., Bergquist, A., Lindstrom, L., Snowdon, V., Trunecka, P., Salizzoni, M., Arendtsen Rostved, A., Arenga, G., Berlakovich, G. A., Candinas, D., Markovic, S., Troisi, R., van Hoek, B., Kanmaz, T., Dayangac, M., Berney, T., Sforza, D., Gridelli, B., Clavien, P. -A., Hoppe-Lotichius, M., Senninger, N., Lorf, T., Settmacher, U., Cuervas-Mons, V., Bacakoglu, A., Nadalin, S., Serra, V., Pacholczyk, M., Baccarani, U., Dopazo Taboada, C., Berenguer, M., San Juan, F., Detry, O., Stippel, D., Evrard, P., Gugenheim, J., Kilic, M., Fernandez Selles, C., Norena, L. A. H., Melandro, F., Gonzalez-Pinto, I., Nicolini, D., Pardo Sanchez, F., and Neumann-Haefelin, C.
- Subjects
Registrie ,IMPACT ,medicine.medical_treatment ,Medizin ,030230 surgery ,Liver transplantation ,DISEASE ,0302 clinical medicine ,Risk Factors ,Recurrence ,Retrospective Studie ,EPIDEMIOLOGY ,Registries ,POPULATION ,bayesian statistics ,OUTCOMES ,disease recurrence ,liver transplantation ,patient and graft survival ,primary sclerosing cholangitis ,surgical procedures, operative ,Cohort ,primary sclerosing cholangiti ,030211 gastroenterology & hepatology ,Registry data ,Life Sciences & Biomedicine ,Human ,bayesian statistic ,medicine.medical_specialty ,Cholangitis, Sclerosing ,Detailed data ,Primary sclerosing cholangitis ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Retrospective Studies ,Transplantation ,Science & Technology ,Proportional hazards model ,business.industry ,Risk Factor ,Bayes Theorem ,Patient survival ,NATURAL-HISTORY ,medicine.disease ,RISK-FACTORS ,Graft survival ,Surgery ,business - Abstract
Liver transplantation for primary sclerosing cholangitis (PSC) can be complicated by recurrence of PSC (rPSC). This may compromise graft survival but the effect on patient survival is less clear. We investigated the effect of post-transplant rPSC on graft and patient survival in a large European cohort. Registry data from the European Liver Transplant Registry regarding all first transplants for PSC between 1980 and 2015 were supplemented with detailed data on rPSC from 48 out of 138 contributing transplant centres, involving 1,549 patients. Bayesian proportional hazards models were used to investigate the impact of rPSC and other covariates on patient and graft survival. Recurrence of PSC was diagnosed in 259 patients (16.7%) after a median follow-up of 5.0 years (quantile 2.5%-97.5%: 0.4-18.5), with a significant negative impact on both graft (HR 6.7; 95% CI 4.9-9.1) and patient survival (HR 2.3; 95% CI 1.5-3.3). Patients with rPSC underwent significantly more re-transplants than those without rPSC (OR 3.6, 95% CI 2.7-4.8). PSC recurrence has a negative impact on both graft and patient survival, independent of transplant-related covariates. Recurrence of PSC leads to higher number of re-transplantations and a 33% decrease in 10-year graft survival. ispartof: TRANSPLANT INTERNATIONAL vol:34 issue:8 pages:1455-1467 ispartof: location:Switzerland status: published
- Published
- 2021
20. Improved Survival in Liver Transplant Patients Receiving Prolonged-release Tacrolimus-based Immunosuppression in the European Liver Transplant Registry (ELTR): An Extension Study
- Author
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Adam, René, Karam, Vincent, Cailliez, Valérie, Trunečka, Pavel, Samuel, Didier, Tisone, Giuseppe, Němec, Petr, Soubrane, Olivier, Schneeberger, Stefan, Gridelli, Bruno, Bechstein, Wolf O., Risaliti, Andrea, Line, Pal-Dag, Vivarelli, Marco, Rossi, Massimo, Pirenne, Jacques, Klempnauer, Jurgen L., Rummo, Aleh, Di Benedetto, Fabrizio, Zieniewicz, Krzysztof, Troisi, Roberto, Paul, Andreas, Vali, Toomas, Kollmar, Otto, Boudjema, Karim, Hoti, Emir, Colledan, Michele, Pratschke, Johan, Lang, Hauke, Popescu, Irinel, Ericzon, Bo-Goran, Strupas, Kestutis, De Simone, Paolo, Kochs, Eberhard, Heyd, Bruno, Gugenheim, Jean, Pinna, Antonio D., Bennet, William, Kazimi, Mirjalal, Bachellier, Philippe, Wigmore, Stephen J., Rasmussen, Allan, Clavien, Pierre-Alain, Hidalgo, Ernest, O'Grady, John G., Zamboni, Frausto, Kilic, Murat, Duvoux, Christophe, O’Grady, John G., Adam, R, Karam, V, Cailliez, V, Trunecka, P, Samuel, D, Tisone, G, Nemec, P, Soubrane, O, Schneeberger, S, Gridelli, B, Bechstein, W, Risaliti, A, Line, P, Vivarelli, M, Rossi, M, Pirenne, J, Klempnauer, J, Rummo, A, Di Benedetto, F, Zieniewicz, K, Troisi, R, Paul, A, Vali, T, Kollmar, O, Boudjema, K, Hoti, E, Colledan, M, Pratschke, J, Lang, H, Popescu, I, Ericzon, B, Strupas, K, De Simone, P, Kochs, E, Heyd, B, Gugenheim, J, Pinna, A, Bennet, W, Kazimi, M, Bachellier, P, Wigmore, S, Rasmussen, A, Clavien, P, Hidalgo, E, O'Grady, J, Zamboni, F, Kilic, M, and Duvoux, C
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Graft Rejection ,Male ,medicine.medical_specialty ,Time Factors ,Drug Compounding ,medicine.medical_treatment ,Calcineurin Inhibitors ,Medizin ,MEDLINE ,chemical and pharmacologic phenomena ,Liver Transplant ,030230 surgery ,Liver transplantation ,Risk Assessment ,Tacrolimus ,all contributing centers (www.eltr.org) and the European Liver and Intestine Transplant Association (ELITA) ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Prolonged release ,Internal medicine ,medicine ,Humans ,Aged ,Delayed-Action Preparations ,Europe ,Female ,Graft Survival ,Immunosuppressive Agents ,Middle Aged ,Registries ,Retrospective Studies ,Treatment Outcome ,Liver Transplantation ,Transplantation ,business.industry ,Immunosuppression ,Retrospective cohort study ,Settore MED/18 ,3. Good health ,surgical procedures, operative ,030211 gastroenterology & hepatology ,Transplant patient ,business ,Risk assessment - Abstract
BACKGROUND: We compared, through the European Liver Transplant Registry, long-term liver transplantation outcomes with prolonged-release tacrolimus (PR-T) versus immediate-release tacrolimus (IR-T)-based immunosuppression. This retrospective analysis comprises up to 8-year data collected between 2008 and 2016, in an extension of our previously published study. METHODS: Patients with
- Published
- 2019
21. Response to the Comment on 'Injury or Function-What Is Best to Assess Organ Viability Before Liver Graft Implantation?'
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Muller Xavier, Philipp Dutkowski, Schlegel Andrea, Clavien Pierre-Alain, University of Zurich, and Dutkowski, Philipp
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Organ Viability ,Tissue Survival ,medicine.medical_specialty ,business.industry ,Urology ,610 Medicine & health ,Organ Preservation ,2746 Surgery ,Liver Transplantation ,Liver graft ,Liver ,Medicine ,Humans ,Surgery ,business ,Function (biology) ,10217 Clinic for Visceral and Transplantation Surgery - Published
- 2020
22. Control of severe portal bleeding by carrier-bound fibrin sealant
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Apestegui, Carlos, Breitenstein, Stefan, Dutkowski, Philipp, and Clavien, Pierre-Alain
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- 2009
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23. Induction of liver hypertrophy for extended liver surgery and partial liver transplantation: State of the art of parenchyma augmentation–assisted liver surgery.
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Müller, Philip C., Linecker, Michael, Kirimker, Elvan O., Oberkofler, Christian E., Clavien, Pierre-Alain, Balci, Deniz, and Petrowsky, Henrik
- Subjects
LIVER surgery ,LIVER transplantation ,LIVER ,HEPATIC veins ,PORTAL vein ,HYPERTROPHY - Abstract
Background: Liver surgery and transplantation currently represent the only curative treatment options for primary and secondary hepatic malignancies. Despite the ability of the liver to regenerate after tissue loss, 25–30% future liver remnant is considered the minimum requirement to prevent serious risk for post-hepatectomy liver failure. Purpose: The aim of this review is to depict the various interventions for liver parenchyma augmentation–assisting surgery enabling extended liver resections. The article summarizes one- and two-stage procedures with a focus on hypertrophy- and corresponding resection rates. Conclusions: To induce liver parenchymal augmentation prior to hepatectomy, most techniques rely on portal vein occlusion, but more recently inclusion of parenchymal splitting, hepatic vein occlusion, and partial liver transplantation has extended the technical armamentarium. Safely accomplishing major and ultimately total hepatectomy by these techniques requires integration into a meaningful oncological concept. The advent of highly effective chemotherapeutic regimen in the neo-adjuvant, interstage, and adjuvant setting has underlined an aggressive surgical approach in the given setting to convert formerly "palliative" disease into a curative and sometimes in a "chronic" disease. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
24. Automated Insulin Delivery - Continuous Blood Glucose Control During Ex Situ Liver Perfusion.
- Author
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Becker, Dustin, Eshmuminov, Dilmurodjon, Keller, Roman, Mueller, Matteo, Bautista Borrego, Lucia, Hagedorn, Catherine, Duskabilova, Muhayyo, Tibbitt, Mark W., Onder, Christopher, Clavien, Pierre-Alain, Rudolf von Rohr, Philipp, Schuler, Martin J., and Hefti, Max
- Subjects
BLOOD sugar ,PERFUSION ,INSULIN ,LIVER ,LIVER transplantation ,GLUCOSE analysis ,GLUCOSE - Abstract
Objective: With the growing demand for livers in the field of transplantation, interest in normothermic ex situ machine perfusion (NMP) has increased in recent years. This may open the door for novel therapeutic interventions such as repair of suboptimal grafts. For successful long-term NMP of livers, blood glucose (BG) levels need to be maintained in a close to physiological range. Methods: We present an “automated insulin delivery” (AID) system integrated into an NMP system, which automatically adjusts insulin infusion rates based on continuous BG measurements in a closed loop manner during ex situ pig and human liver perfusion. An online glucose sensor for continuous glucose monitoring was integrated and evaluated in blood. A model based and a proportional controller were implemented and compared in their ability to maintain BG within the physiological range. Results: The continuous glucose sensor is capable of measuring BG directly in human and pig blood for multiple days with an average error of 0.6 mmol/L. There was no significant difference in the performance of the two controllers in terms of their ability to keep BG in the physiological range. With the integrated AID, BG was controlled within the physiological range on average in 80% and 76% of the perfusion time for human and pig livers, respectively. Conclusion: The presented work offers a method and shows the feasibility to maintain BG in the physiological range for multiple (up to ten) days during ex situ liver perfusion with the help of an automated AID. Significance: Maintaining BG within the physiological range is required to enable long-term ex situ liver perfusion. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
25. Hypothermic Oxygenated Perfusion Versus Normothermic Regional Perfusion in Liver Transplantation From Controlled Donation After Circulatory Death: First International Comparative Study.
- Author
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Muller, Xavier, Mohkam, Kayvan, Mueller, Matteo, Schlegel, Andrea, Dondero, Federica, Sepulveda, Ailton, Savier, Eric, Scatton, Olivier, Bucur, Petru, Salame, Ephrem, Jeddou, Heithem, Sulpice, Laurent, Pittau, Gabriella, Allard, Marc-Antoine, Mabrut, Jean-Yves, Dutkowski, Philipp, Clavien, Pierre-Alain, and Lesurtel, Mickael
- Abstract
Objective: To compare HOPE and NRP in liver transplantation from cDCD. Summary of Background Data: Liver transplantation after cDCD is associated with higher rates of graft loss. Dynamic preservation strategies such as NRP and HOPE may offer safer use of cDCD grafts. Methods: Retrospective comparative cohort study assessing outcomes after cDCD liver transplantation in 1 Swiss (HOPE) and 6 French (NRP) centers. The primary endpoint was 1-year tumor-death censored graft and patient survival. Results: A total of 132 and 93 liver grafts were transplanted after NRP and HOPE, respectively. NRP grafts were procured from younger donors (50 vs 61 years, P < 0.001), with shorter functional donor warm ischemia (22 vs 31 minutes, P < 0.001) and a lower overall predicted risk for graft loss (UK-DCD-risk score 6 vs 9 points, P < 0.001). One-year tumor-death censored graft and patient survival was 93% versus 86% (P = 0.125) and 95% versus 93% (P = 0.482) after NRP and HOPE, respectively. No differences in non-anastomotic biliary strictures, primary nonfunction and hepatic artery thrombosis were observed in the total cohort and in 32 vs. 32 propensity score-matched recipients Conclusion: NRP and HOPE in cDCD achieved similar post-transplant recipient and graft survival rates exceeding 85% and comparable to the benchmark values observed in standard DBD liver transplantation. Grafts in the HOPE cohort were procured from older donors and had longer warm ischemia times, and consequently achieved higher utilization rates. Therefore, randomized controlled trials with intention-to-treat analysis are needed to further compare both preservation strategies, especially for high-risk donor-recipient combinations. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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26. Hypothermic Oxygenated Liver Perfusion (HOPE) Prevents Tumor Recurrence in Liver Transplantation From Donation After Circulatory Death.
- Author
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Mueller, Matteo, Kalisvaart, Marit, O‘Rourke, Joanne, Shetty, Shishir, Parente, Alessandro, Muller, Xavier, Isaac, John, Muellhaupt, Beat, Muiesan, Paolo, Shah, Tahir, Clavien, Pierre-Alain, Schlegel, Andrea, and Dutkowski, Philipp
- Abstract
Objective: The aim of this study was to investigate tumor recurrence after liver transplantation for hepatocellular carcinoma (HCC), with and without hypothermic oxygenated liver perfusion (HOPE) before transplantation. Patients and Methods: We analyzed all liver recipients with HCC, transplanted between January 2012 and September 2019 with donation after circulatory death (DCD) livers after previous end-ischemic HOPE-treatment (n = 70, Center A). Tumor parameters and key confounders were compared to consecutive recipients with HCC, transplanted during the same observation period with an unperfused DBD liver (n = 70). In a next step, we analyzed unperfused DCD (n = 70) and DBD liver recipients (n = 70), transplanted for HCC at an external center (Center B). Results: Tumor parameters were not significantly different between HOPE-treated DCD and unperfused DBD liver recipients at Center A. One-third of patients were outside established tumor thresholds, for example, Milan criteria, in both groups. Despite no difference in tumor load, we found a 4-fold higher tumor recurrence rate in unperfused DBD livers (25.7%, 18/70), compared to only 5.7% (n = 4/70) recipients with tumor recurrence in the HOPE-treated DCD cohort (P = 0.002) in Center A. The tumor recurrence rate was also twice higher in unperfused DCD and DBD recipients at the external Center B, despite significant less cases outside Milan. HOPE-treatment of DCD livers resulted therefore in a 5-year tumor-free survival of 92% in HCC recipients, compared to 73%, 82.7%, and 81.2% in patients receiving unperfused DBD or DCD livers, from both centers. Conclusion: We suggest that a simple machine liver perfusion approach appears advantageous to protect from HCC recurrence after liver transplantation, despite extended tumor criteria. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
27. Novel Real-time Prediction of Liver Graft Function During Hypothermic Oxygenated Machine Perfusion Before Liver Transplantation.
- Author
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Muller, Xavier, Schlegel, Andrea, Kron, Philipp, Eshmuminov, Dilmurodjon, Würdinger, Michael, Meierhofer, David, Clavien, Pierre-Alain, and Dutkowski, Philipp
- Abstract
Objective: The aim of this study was to determine the predictive value of machine perfusate analysis on graft outcome. Background: Ex situ machine perfusion (MP) is gaining increasing interest to potentially repair injured organs and to assess organ function. In the field of liver transplantation, however, no studies exist on reliable prediction of graft function during MP. Methods: We have used hypothermic oxygenated perfusion (HOPE) for donation after circulatory death (DCD) or extended criteria donation after brain death (DBD) human liver grafts during the last 7 years. Our series includes 100 HOPE-treated liver-transplanted patients with an overall tumor-censored 5-year graft survival of 89%. We monitored 54 livers during HOPE in terms of fluorometric analysis of released mitochondrial flavin (flavin mononucleotide, FMN) in the machine perfusate. Results: Real-time optical measurement of mitochondrial FMN release in machine perfusates of livers disclosed a strong correlation with lactate clearance and coagulation factors at day 1 and 2 after transplantation. Receiver-operating characteristic curve analysis revealed an area under the curve (AUROC) of 0.79 [95% confidence interval (CI), 0.62-0.97] for severe allograft dysfunction and for early graft loss (AUROC 0.93, 95% CI, 0.84-1.0). Conclusions: Assessment of flavin, a marker of mitochondrial complex I injury, in the perfusate provides a fast prediction of liver graft function and loss during ex situ MP before implantation. This finding may have high clinical relevance, as liver grafts from extended DBD or DCD donors carry considerable risks for recipients. On-line estimation of outcome before implantation would therefore substantially increase safe utilization of liver grafts. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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28. Exogenous melatonin protects small‐for‐size liver grafts by promoting monocyte infiltration and releases interleukin‐6.
- Author
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Song, Zhuolun, Humar, Bostjan, Gupta, Anurag, Maurizio, Eleonora, Borgeaud, Nathalie, Graf, Rolf, Clavien, Pierre‐Alain, and Tian, Yinghua
- Subjects
PHYSIOLOGICAL effects of melatonin ,LIVER transplantation ,MONOCYTES ,INTERLEUKIN-6 ,REGENERATION (Biology) - Abstract
Abstract: Defective regeneration of small‐for‐size (SFS) liver remnants and partial grafts remains a key limiting factor in the application of liver surgery and transplantation. Exogenous melatonin (MLT) has protective effects on hepatic ischemia‐reperfusion injury (IRI), but its influence on graft regeneration is unknown. The aim of the study is to investigate the role of MLT in IRI and graft regeneration in settings of partial liver transplantation. We established three mouse models to study hepatic IRI and regeneration associated with partial liver transplantation: (I) IR+PH group: 60 minutes liver ischemia (IR) plus 2/3 hepatectomy (PH); (II) IR+exPH group: 60 minutes liver IR plus extended hepatectomy (exPH) associated with the SFS syndrome; (III) SFS‐LT group: Arterialized 30% SFS liver transplant. Each group was divided into MLT or vehicle‐treated subgroups. Hepatic injury, inflammatory signatures, liver regeneration, and animal survival rates were assessed. MLT reduced liver injury, enhanced liver regeneration, and promoted interleukin (IL) 6, IL10, and tumor necrosis factor‐α release by infiltrating, inflammatory Ly6C+ F4/80+ monocytes in the IR+PH group. MLT‐induced IL6 significantly improved hepatic microcirculation and survival in the IR+exPH model. In the SFS‐LT group, MLT promoted graft regeneration and increased recipient survival along with increased IL6/GP130‐STAT3 signaling. In IL6
−/− mice, MLT failed to promote liver recovery, which could be restored through recombinant IL6. In the IR+exPH and SFS‐LT groups, inhibition of the IL6 co‐receptor GP130 through SC144 abolished the beneficial effects of MLT. MLT ameliorates SFS liver graft IRI and restores regeneration through monocyte‐released IL6 and downstream IL6/GP130‐STAT3 signaling. [ABSTRACT FROM AUTHOR]- Published
- 2018
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29. Liver transplantation for erythropoietic protoporphyria in Europe
- Author
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Wahlin, Staffan, Stal, Per, Adam, Rene, Karam, Vincent, Porte, Robert, Seehofer, Daniel, Gunson, Bridget K., Hillingsø, Jens, Klempnauer, Jürgen L., Schmidt, Jan, Alexander, Graeme, O'Grady, John, Clavien, Pierre-Alain, Salizzoni, Mauro, Paul, Andreas, Rolles, Keith, Ericzon, Bo-Göran, Harper, Pauline, University of Zurich, Wahlin, S, Faculteit Medische Wetenschappen/UMCG, and Groningen Institute for Organ Transplantation (GIOT)
- Subjects
Adult ,Male ,Risk ,Adolescent ,Protoporphyria, Erythropoietic ,2747 Transplantation ,Medizin ,610 Medicine & health ,PATIENT ,DISEASE ,Recurrence ,FAILURE ,Humans ,Child ,10217 Clinic for Visceral and Transplantation Surgery ,Demography ,Retrospective Studies ,COMPLICATIONS ,Middle Aged ,2746 Surgery ,Liver Transplantation ,Europe ,Treatment Outcome ,2721 Hepatology ,Female ,Liver Failure ,Stem Cell Transplantation - Abstract
Liver transplantation is an established lifesaving treatment for patients with severe protoporphyric liver disease, but disease recurrence in the graft occurs for the majority of recipients. Severe burn injuries may occur when protective light filters are not used with surgical luminaires. Motor neuropathy with an unclear pathogenesis is a frequent complication. We retrospectively studied 35 transplants performed for protoporphyric liver disease in 31 European patients between 1983 and 2008. Most of the patients were male (61.3%), and the mean age at the time of primary transplantation was 39 years (range = 9-60 years). The overall patient survival rates were 77% at 1 year and 66% at 5 and 10 years. The overall rate of disease recurrence in the graft was 69%. Forty-three percent of the patients experienced recurrence within a year, but this was often a transient finding that was associated with other graft complications. Phototoxic injuries due to surgical luminaires were seen in 25.0% of the patients who were not protected by filters, but these injuries were not seen in the 9 patients who were protected by filters. Significant motor neuropathies requiring prolonged ventilation complicated the postoperative course for 5 of the 31 patients (16.1%). Hematopoietic stem cell transplantation was performed for 3 patients to prevent graft loss due to disease recurrence. Prognostic markers are needed to identify patients prone to severe protoporphyric liver disease so that curative stem cell transplantation can be offered to select patients instead of liver transplantation. Liver Transpl 17: 1021-1026, 2011. (C) 2011 AASLD.
- Published
- 2011
30. Laparoscopic Living Donor Left Lateral Sectionectomy: A New Standard Practice for Donor Hepatectomy.
- Author
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Soubrane, Olivier, de Rougemont, Olivier, Ki-Hun Kim, Samstein, Benjamin, Mamode, Nizam, Boillot, Olivier, Troisi, Roberto I., Scatton, Olivier, Cauchy, François, Sung-Gyu Lee, Griesemer, Adam, Ahmed, Zubir, Clavien, Pierre-Alain, and Cherqui, Daniel
- Abstract
Objective: The aim of the study was to compare the short-term donor outcomes of laparoscopic left lateral sectionectomy (LLLS) for adult to child living donor liver transplantation (A-C LDLT) and laparoscopic donor nephrectomy (LDN). Background: Although laparoscopy has become the standard approach in kidney donors, its use remains limited and controversial in LLS for A-C LDLT due to the lack of conclusive assessment of procedure-related morbidity. Methods: From 2001 to 2014, 124 healthy donors undergoing laparoscopic LLLS for A-C LDLT at 5 tertiary referral centers in Europe, North America, and Asia, and 300 healthy donors undergoing LDN at 2 tertiary centers in Europe were retrospectively analyzed. The outcomes of LLLS were compared with those of LDN including the use of the comprehensive complication index (CCI). Results: Although liver donors experienced significantly less overall (16.9% vs 31.7%, P=0.002) and grade 1 to 2 (12.1% vs 24.7%, P=0.004) complications than kidney donors, the rates of major complication (⩾ grade 3) were similar between the 2 groups. In both groups, donors experiencing postoperative complications had similar CCI (19.3 vs 21.9 for liver and kidney donors, respectively, P=0.29). After propensity score analysis allowing for matching donors on age, sex, and body mass index, the postoperative outcomes remained comparable between the 2 groups. Conclusion: Laparoscopic LLS for A-C LDLT yields at least similar shortterm donor outcomes as LDN. These results provide the first validation for a laparoscopic donor hepatectomy and suggest that the laparoscopic approach should be considered a new standard practice for retrieval of left lateral section liver grafts as it is for kidney donation. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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- View/download PDF
31. Challenges to Liver Transplantation and Strategies to Improve Outcomes.
- Author
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Dutkowski, Philipp, Linecker, Michael, DeOliveira, Michelle L., Müllhaupt, Beat, and Clavien, Pierre-Alain
- Abstract
Liver transplantation (LT) is a highly successful treatment for many patients with nonmalignant and malignant liver diseases. However, there is a worldwide shortage of available organs; many patients deteriorate or die while on waiting lists. We review the important clinical challenges to LT and the best use of the scarce organs. We focus on changes in indications for LT and discuss scoring systems to best match donors with recipients and optimize outcomes, particularly for the sickest patients. We also cover controversial guidelines for the use of LT in patients with hepatocellular carcinoma and cholangiocarcinoma. Strategies to increase the number of functional donor organs involve techniques to perfuse the organs before implantation. Partial LT (living donor and split liver transplantation) techniques might help to overcome organ shortages, and we discuss small-for-size syndrome. Many new developments could increase the success of this procedure, which is already one of the major achievements in medicine during the second part of the 20th century. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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32. Novel rescue procedure for inferior vena cava reconstruction in living-donor liver transplantation using a vascular graft recovered 25 h after donors' circulatory death and systematic review.
- Author
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Palma, Adrian F., Oberkofler, Christian E., Raptis, Dimitri A., Eshmuminov, Dilmurodjon, Rougemont, Olivier, Schnyder, Aurelia, Dimitroulis, Dimitrios, Lesurtel, Mickael, Dutkowski, Philipp, and Clavien, Pierre-Alain
- Subjects
INFERIOR vena cava surgery ,LIVER transplantation ,VASCULAR grafts ,ANGIOSARCOMA ,ORGAN donors ,PATIENTS - Abstract
Liver transplantation is a lifesaving treatment for patients suffering from end-stage liver disease. Rarely, acute congestion of the inferior vena cava ( IVC) is being encountered because of tumor compression. MELD allocation does not reflect severity of this condition because of lack of organ failure. Herein, a patient is being presented undergoing urgent living-donor liver transplantation ( LDLT) with IVC reconstruction for a fast-growing hepatic epithelioid hemangioendothelioma ( HEH). IVC reconstruction using a venous graft recovered from a 25-h after circulatory-death prior transplantation became necessary to compensate severe venous congestion. Additionally, a systematic review of the literature searching MEDLINE/ Pub Med was performed. Protocol and eligibility criteria were specified in advance and registered at the PROSPERO registry ( CRD42013004827). Published literature of IVC reconstruction in LDLT was selected. Two reports describing IVC reconstruction with cryopreserved IVC grafts and one IVC reconstruction using a deceased after-circulatory-death-donor IVC graft were included. Follow-up was at 12 and 13 months, respectively. Regarding the graft recovery in the setting of living-related donation, this graft remained patent during the nine-month follow-up period. This is the first report on the use of a venous graft from a circulatory-death-donor, not eligible for whole organ recovery. We demonstrate in this study the feasibility of using a size and blood-group-compatible IVC graft from a cold-stored donor, which can solve the problem of urgent IVC reconstruction in patients undergoing LDLT. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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33. Multimodal Treatment Strategies in Patients Undergoing Surgery for Hepatocellular Carcinoma.
- Author
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Lurje, Georg, Lesurtel, Mickaël, and Clavien, Pierre-Alain
- Abstract
Hepatocellular carcinoma (HCC) is one of the major health problems worldwide, and continues to grow because of its association with hepatitis B and C viruses. In patients with HCC, liver transplantation (LT) and liver resection are the only two curative treatment options. LT remains the best option since it not only removes the tumor, but also the underlying disease. The prerequisite for long-term success of LT for HCC depends on the tumor load and strict selection criteria with regard to the size and number of existing HCC lesions. The need to obtain the optimal benefit from a limited number of grafts has prompted the implementation of well-defined selection criteria that identify patients with early HCC who may benefit from better long-term outcome after LT. Unfortunately, LT can only be proposed in approximately 30% of patients with HCC due to limitations in donor graft availability. In this particular setting, open and laparoscopic surgical resection represent reasonable treatment modalities in noncirrhotic HCC patients. The decision-making process for liver resection should integrate the tumor stage, quality and function of the underlying liver parenchyma, volume of the future liver remnant, and general condition of the patient. In patients with favorable features (solitary tumor, compensated Child-Pugh A cirrhosis, no portal hypertension), the reported 5-year survival rates range between 50 and 70%. In specific cases, liver resection and LT may be combined in the same patient. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
- Published
- 2013
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34. “State of the Art” in Liver Resection and Living Donor Liver Transplantation: A Worldwide Survey of 100 Liver Centers.
- Author
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Breitenstein, Stefan, Apestegui, Carlos, Petrowsky, Henrik, and Clavien, Pierre Alain
- Subjects
LIVER surgery ,SURGICAL excision ,LIVER biopsy ,LIVER transplantation ,MEDICAL care surveys - Abstract
New strategies have been developed to expand indications for liver surgery. The objective was to evaluate the current practice worldwide regarding critical liver mass and manipulation of the liver volume. A survey was sent to 133 liver centers worldwide, which focused on (a) critical liver volume, (b) preoperative manipulation of the liver mass, and (c) use of liver biopsy and metabolic tests. The overall response rate to the survey was 75%. Half of the centers performed more than 100 resections per year; 86% had an associated liver transplant program. The minimal remnant liver volume for resection was 25% (15–40%) in cases of normal liver parenchyma and 50% (25–90%) in the presence of underlying cirrhosis. The minimal remnant liver volume for living donors was 40% (30–50%), whereas the accepted graft body weight ratio was 0.8 (0.6–1.2). Portal vein occlusion to manipulate the liver volume before resection was performed in 89% of the centers. Limits of liver volume and the current practice of liver manipulation before resection were comparable among different centers and continents. The minimal remnant liver volume in normal liver was 25%, and more than 80% of the centers performed portal vein occlusion. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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- View/download PDF
35. Strategies for Safer Liver Surgery and Partial Liver Transplantation.
- Author
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Clavien, Pierre-Alain, Petrowsky, Henrik, DeOliveira, Michelle L., and Graf, Rolf
- Subjects
- *
LIVER transplantation , *LIVER regeneration , *REGENERATION (Biology) , *TRANSPLANTATION of organs, tissues, etc. , *LIVER surgery , *LIVER blood-vessels , *HEPATIC artery , *PORTAL vein - Abstract
The article discusses medical strategies that can ensure safer practices in liver surgery and partial liver transplantation. The ability of the liver to regenerate is discussed, as is the anatomy and physiology of the liver. The two major blood vessels of the liver are the hepatic artery and the portal vein. In a liver transplantation, a partial liver graft is obtained from a deceased or living donor. The preoperative evaluation of the potential liver donation is critical. Drugs that can be used to protect the liver during regeneration are discussed.
- Published
- 2007
36. Kupffer cell-dependent TNF-α signaling mediates injury in the arterialized small-for-size liver transplantation in the mouse.
- Author
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Yinghua Tian, Jochum, Wolfram, Georgiev, Panco, Moritz, Wolfgang, Graf, Roif, and Clavien, Pierre-Alain
- Subjects
LIVER transplantation ,TUMOR necrosis factors ,MICE ,REGENERATION (Biology) ,INTERLEUKIN-6 ,CELL adhesion - Abstract
Implantation of small liver grafts causes liver injury and defective regeneration leading to graft failure. We investigated whether Kupffer cell-dependent TNF-α signaling contributes to this poor outcome. Partial 30% liver transplantation was performed in C57BL/6 wild-type mice (control group), and in three groups with down-regulation of the TNF-α pathway: (i) TNF receptor 1 knock-out [TNFR-1(-/-)] mice, and mice pretreated with (ii) gadolinium chloride or (iii) pentoxifylline (PTX). Fifty-percent partial liver transplantation, a model associated with full recovery, and transplantation in IL-6 knockout [lL-6(-/-)] mice were performed in some experiments. Graft injury, regeneration, portal flow, liver microcirculation, leukocyte adhesion, and animal survival were assessed. Animal survival rates were 14% in the control group vs. 43% in the gadolinium chloride group, 57% for the TNFR-1(-/-) group, and 86% in the PTX group (P < 0.001). Markers of liver injury were reduced in all treated groups when compared with controls. Each treated group disclosed better portal flow and sinusoid perfusion, decreased leukocyte adherence, particularly in the PTX group. Liver regeneration occurred only in the treated groups. lL-6 and IL-b levels were dramatically up-regulated (50x) in the PTX group, and at lower levels in other experimental groups. The protective effect of PTX was lost in lL-6(-/-) mice and protection was restored by a single dose of r-IL-6. In conclusion, interruption of TNF-α signaling or depletion of Kupffer cells improves survival after 30% liver transplantation, reduces liver injury, and enhances regeneration. The superior effects of PTX are mediated by IL-6. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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- View/download PDF
37. Ribavirin/interferon-α sequential treatment of recurrent hepatitis C after liver transplantation.
- Author
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Giostra, Emiliano, Kullak-Ublick, Gerd A., Keller, Walter, Fried, Ronald, Vanlemmens, Claire, Kraehenbuhl, Stephan, Locher, Sandrine, Egger, Hans-Peter, Clavien, Pierre-Alain, Hadengue, Antoine, Mentha, Gilles, Morel, Philippe, and Negro, Francesco
- Subjects
HEPATITIS C ,LIVER transplantation ,RIBAVIRIN ,GENETIC polymorphisms ,INTERFERONS ,HEPATITIS C virus ,VIRAL hepatitis - Abstract
Hepatitis C virus (H CV) infection invariably recurs after liver transplantation (LT), and sequels of chronic hepatitis of the graft are a significant cause of morbidity and mortality. In an uncontrolled trial, 31 patients with histologically confirmed hepatitis C after LT received, sequentially, ribavirin (10 mg/kg body weight q.d.) for 12 weeks, followed by ribavirin at the same dose q.d. plus interferon-α (IFN-α) [3 million units three times a week (3 MU TIW)] for another 48 weeks. Based on an intent-to-treat analysis, the percentages of patients with undetectable HCV RNA in their serum were 0%, 38.7% and 45.2% after 12, 36 and 60 weeks of therapy, respectively. A sustained virological response, as defined by undetectable serum HCV RNA 24 weeks after the end of treatment, was observed in 9/31 patients (29%). Sustained responders had a significant improvement of their liver inflammatory activity score (P = 0.025), but not of their liver fibrosis score. The chances of sustained virological response correlated with the length of treatment, but not with the HCV genotype or baseline HCV RNA level. In conclusion, patients with recurrent hepatitis C after LT might benefit from ribavirin/IFN-α therapy, provided that the treatment is tolerated for a sufficient duration of time. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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- View/download PDF
38. Reply to "Ex situ normothermic machine perfusion of donor livers using a haemoglobin‐based oxygen carrier: a viable alternative to red blood cells".
- Author
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Eshmuminov, Dilmurodjon, Leoni, Filippo, Schneider, Marcel André, Becker, Dustin, Muller, Xavier, Hefti, Max, Schuler, Martin J., Onder, Christopher, Dutkowski, Philipp, Graf, Rolf, Rudolf von Rohr, Philipp, Clavien, Pierre‐Alain, and Bautista Borrego, Lucia
- Subjects
PERFUSION ,LIVER transplantation ,OXYGEN carriers - Published
- 2018
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39. A novel technique in mouse liver transplantation.
- Author
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Tian, Yinghua, Lesurtel, Mickael, Ungethuem, Udo, Song, Zhuolun, Maurizio, Eleonora, and Clavien, Pierre-Alain
- Subjects
LIVER transplantation ,BILE duct surgery ,SURGERY ,ISOFLURANE ,SURGICAL anastomosis - Abstract
The article reports a novel method of main bile duct reconstruction in a mouse liver transplantation (LT) using cholecystojejunostomy (CJ) anatomosis. Surgical procedure involves the mouse LT performed under a surgical microscope in mice anesthetized with isoflurane plus oxygen inhalation. It cites CJ as an easy alternative to the challenging end-to-end bile duct anastomosis in mouse LT which can be used in experiments where stent method is not feasible.
- Published
- 2016
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- View/download PDF
40. Are patients with hepatocellular carcinoma and portal vein tumour thrombosis candidates for liver transplantation?
- Author
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Soin, Arvinder, Lesurtel, Mickaël, Bhangui, Prashant, Cocchi, Lorenzo, Bouattour, Mohamed, and Clavien, Pierre-Alain
- Subjects
- *
PORTAL vein , *LIVER transplantation , *HEPATOCELLULAR carcinoma , *PATIENT portals , *THROMBOSIS - Abstract
In this debate, the authors consider whether patients with hepatocellular carcinoma (HCC) and portal vein tumour thrombosis are candidates for liver transplantation (LT). The argument for LT in this context is based on the premise that, following successful downstaging treatment, LT confers a much greater clinical benefit in terms of survival outcomes than the available alternative (palliative systemic therapy). A major argument against relates to limitations in the quality of evidence for LT in this setting – in relation to study design, as well as heterogeneity in patient characteristics and downstaging protocols. While acknowledging the superior outcomes offered by LT for patients with portal vein tumour thrombosis, the counterargument is that expected survival in such patients is still below accepted thresholds for LT and, indeed, the levels achieved for other patients who receive transplants beyond the Milan criteria. Based on the available evidence, it seems too early for consensus guidelines to recommend such an approach, however, it is hoped that with higher quality evidence and standardised downstaging protocols, LT may soon be more widely indicated, including for this population with high unmet clinical need. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
41. Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report
- Author
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Clavien, Pierre-Alain, Lesurtel, Mickael, Bossuyt, Patrick MM, Gores, Gregory J, Langer, Bernard, and Perrier, Arnaud
- Subjects
- *
LIVER cancer , *LIVER transplantation , *CONFERENCES & conventions , *CANCER patients , *GUIDELINES - Abstract
Summary: Although liver transplantation is a widely accepted treatment for hepatocellular carcinoma (HCC), much controversy remains and there is no generally accepted set of guidelines. An international consensus conference was held on Dec 2–4, 2010, in Zurich, Switzerland, with the aim of reviewing current practice regarding liver transplantation in patients with HCC and to develop internationally accepted statements and guidelines. The format of the conference was based on the Danish model. 19 working groups of experts prepared evidence-based reviews according to the Oxford classification, and drafted recommendations answering 19 specific questions. An independent jury of nine members was appointed to review these submissions and make final recommendations, after debates with the experts and audience at the conference. This report presents the final 37 statements and recommendations, covering assessment of candidates for liver transplantation, criteria for listing in cirrhotic and non-cirrhotic patients, role of tumour downstaging, management of patients on the waiting list, role of living donation, and post-transplant management. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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- View/download PDF
42. Ischemia/Reperfusion Injury in Liver Surgery and Transplantation.
- Author
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Schemmer, Peter, Lemasters, John J., and Clavien, Pierre-Alain
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LIVER surgery ,LIVER transplantation ,SURGICAL complications ,COMPLICATIONS from organ transplantation - Abstract
The authors discuss lack of guarantee for adequate liver function after liver resection and transplantation due to ischemia/reperfusion injury (IRI). They claim that IRI is unavoidable in liver transplantation (LT) and that up to 88% of patients report poor graft function after LT. The authors cite factors that contribute to IRI, which include preexisting damage and reperfusion.
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- 2012
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43. Hepcidin Expression Does Not Rescue the Iron-Poor Phenotype of Kupffer Cells in Hfe-Null Mice After Liver Transplantation.
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Garuti, Cinzia, Tian, Yinghua, Montosi, Giuliana, Sabelli, Manuela, Corradini, Elena, Graf, Rolf, Ventura, Paolo, Vegetti, Alberto, Clavien, Pierre–Alain, and Pietrangelo, Antonello
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HEMOCHROMATOSIS ,KUPFFER cells ,LIVER transplantation ,LABORATORY mice ,MICRONUTRIENTS ,POLYMERASE chain reaction ,STANDARD deviations ,HISTOPATHOLOGY - Abstract
Background & Aims: Hemochromatosis is a common hereditary disease caused by mutations in HFE and characterized by increased absorption of iron in the intestine. However, the intestine does not appear to be the site of mutant HFE activity in the disease; we investigated the role of the liver—the source of the iron regulatory hormone hepcidin—in pathogenesis in mice. Methods: We exchanged livers between Hfe wild-type (+/+) and Hfe null (−/−) mice by orthotopic liver transplantation (OLT) and assessed histopathology, serum and tissue iron parameters, and hepatic hepcidin messenger RNA expression. Results: At 6–8 months after OLT, Hfe
−/− mice that received Hfe−/− livers maintained the hemochromatosis phenotype: iron accumulation in hepatocytes but not Kupffer cells (KC), increased transferrin levels, and low levels of iron in the spleen. Hfe+/+ mice that received Hfe−/− livers had increased levels of iron in serum and liver and low levels of iron in spleen. However, they did not develop the iron-poor KCs that characterize hemochromatosis: KCs appeared iron rich, although hepatic hepcidin expression was low. Transplantation of Hfe+/+ livers into Hfe−/− mice prevented hepatic iron accumulation but did not return spleen and plasma levels of iron to normal; KCs still appeared to be iron poor, despite normal hepcidin expression. Conclusions: In Hfe−/− mice, transplantation of livers from Hfe+/+ mice reversed the iron-loading phenotype associated with hemochromatosis (regardless of Hfe expression in intestine). However, KCs still had low levels of iron that were not affected by hepatic hepcidin expression. These findings indicate an independent, iron-modifying effect of HFE in KCs. [Copyright &y& Elsevier]- Published
- 2010
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44. “State of the Art” in Liver Resection and Living Donor Liver Transplantation: A Worldwide Survey of 100 Liver Centers—Reply to Letter.
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Breitenstein, Stefan and Clavien, Pierre-Alain
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LETTERS to the editor , *LIVER transplantation - Abstract
A response by Stefan Breitenstein and Pierre-Alain Clavien to a letter to the editor about their article "State of the Art in Liver Resection and Living Donor Liver Transplantation: A Worldwide Survey of 100 Liver Centers," published in the previous issue is presented.
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- 2010
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45. Hypothermic oxygenated perfusion (HOPE) protects from biliary injury in a rodent model of DCD liver transplantation.
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Schlegel, Andrea, Graf, Rolf, Clavien, Pierre-Alain, and Dutkowski, Philipp
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CARDIAC arrest , *PERFUSION , *LIVER transplantation , *ORGAN donation , *ISCHEMIA , *REACTIVE oxygen species , *LABORATORY mice - Abstract
Background & Aims: The use of livers from donors after cardiac arrest (DCD) is increasing in many countries to overcome organ shortage. Due to additional warm ischemia before preservation, those grafts are at higher risk of failure and bile duct injury. Several competing rescue strategies by machine perfusion techniques have been developed with, however, unclear effects on biliary injury. We analyze the impact of an end-ischemic Hypothermic Oxygenated PErfusion (HOPE) approach applied only through the portal vein for 1h before graft implantation. Methods: Rat livers were subjected to 30-min in situ warm ischemia, followed by subsequent 4-h cold storage, mimicking DCD-organ procurement and conventional organ transport. Livers in the HOPE group underwent also passive cold storage for 4h, but were subsequently machine perfused for 1h before implantation. Outcome was tested by liver transplantation (LT) at 12h after implantation (n=10 each group) and after 4weeks (n=10 each group), focusing on early reperfusion injury, immune response, and later intrahepatic biliary injury. Results: All animals survived after LT. However, reperfusion injury was significantly decreased by HOPE treatment as tested by hepatocyte injury, Kupffer cell activation, and endothelial cell activation. Recipients receiving non-perfused DCD livers disclosed less body weight gain, increased bilirubin, and severe intrahepatic biliary fibrosis. In contrast, HOPE treated DCD livers were protected from biliary injury, as detected by cholestasis parameter and histology. Conclusions: We demonstrate in a DCD liver transplant model that end-ischemic hypothermic oxygenated perfusion is a powerful strategy for protection against biliary injury. [Copyright &y& Elsevier]
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- 2013
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46. Reply to: “The rescue of DCD rodent livers grafts: Is there HOPE?”.
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Schlegel, Andrea, Dutkowski, Philipp, and Clavien, Pierre-Alain
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- *
LIVER transplantation , *CARDIAC arrest , *ORGAN donors , *PERFUSION , *LIVER physiology , *HEPATOLOGY - Published
- 2015
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47. Allocation of liver grafts worldwide – Is there a best system?
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Tschuor, Christoph, Ferrarese, Alberto, Kuemmerli, Christoph, Dutkowski, Philipp, Burra, Patrizia, and Clavien, Pierre-Alain
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LIVER transplantation , *LIVER , *LIVER diseases - Abstract
• An optimal allocation system for scarce resources should simultaneously ensure maximal utility, but also equity. • Large differences exist between centers and countries for ethical and legislative reasons. • A future globally applicable strategy should combine donor and recipient factors. • This strategy must predict probability of death on the waiting list, post-transplant survival and morbidity, and costs. An optimal allocation system for scarce resources should simultaneously ensure maximal utility, but also equity. The most frequent principles for allocation policies in liver transplantation are therefore criteria that rely on pre-transplant survival (sickest first policy), post-transplant survival (utility), or on their combination (benefit). However, large differences exist between centers and countries for ethical and legislative reasons. The aim of this study was to report the current worldwide practice of liver graft allocation and discuss respective advantages and disadvantages. Countries around the world that perform 95 or more deceased donor liver transplantations per year were analyzed for donation and allocation policies, as well as recipient characteristics. Most countries use the model for end-stage liver disease (MELD) score, or variations of it, for organ allocation, while some countries opt for center-based allocation systems based on their specific requirements, and some countries combine both a MELD and center-based approach. Both the MELD and center-specific allocation systems have inherent limitations. For example, most countries or allocation systems address the limitations of the MELD system by adding extra points to recipient's laboratory scores based on clinical information. It is also clear from this study that cancer, as an indication for liver transplantation, requires special attention. The sickest first policy is the most reasonable basis for the allocation of liver grafts. While MELD is currently the standard for this model, many adjustments were implemented in most countries. A future globally applicable strategy should combine donor and recipient factors, predicting probability of death on the waiting list, post-transplant survival and morbidity, and perhaps costs. An optimal allocation system for scarce resources should simultaneously ensure maximal utility, but also equity. While the model for end-stage liver disease is currently the standard for this model, many adjustments were implemented in most countries. A future globally applicable strategy should combine donor and recipient factors predicting probability of death on the waiting list, post-transplant survival and morbidity, and perhaps costs. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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48. Outcomes of DCD liver transplantation using organs treated by hypothermic oxygenated perfusion before implantation.
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Schlegel, Andrea, Muller, Xavier, Kalisvaart, Marit, Muellhaupt, Beat, Perera, M. Thamara P.R., Isaac, John R., Clavien, Pierre-Alain, Muiesan, Paolo, and Dutkowski, Philipp
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- *
LIVER transplantation , *PERFUSION , *BRAIN death , *ISCHEMIA , *CANCER-related mortality - Abstract
Graphical abstract Highlights • End-ischemic HOPE protected against arterial and biliary complications, resulting in significantly less graft loss. • Equivalent outcomes were achieved with HOPE as with primary DBD liver transplants. • HOPE after cold storage is a simple and effective method to treat high-risk DCD livers prior to implantation. Background & Aims Donation after circulatory death (DCD) liver transplantation is known for potentially worse outcomes because of higher rates of graft non-function or irreversible cholangiopathy. The impact of machine liver perfusion techniques on these complications remains elusive. We aimed to provide data on 5-year outcomes in patients receiving DCD liver transplants, after donor organs had been treated by hypothermic oxygenated perfusion (HOPE). Methods Fifty HOPE-treated DCD liver transplants performed in Zurich between 2012 and 3/2017 were matched with 50 primary donation after brain death (DBD) liver transplants, and with 50 untreated DCD liver transplants in Birmingham. Match factors focussed on short cold ischaemia, comparable recipient age and low recipient laboratory model for end-stage liver disease scores. Primary endpoints were post-transplant complications, and non-tumour-related patient death or graft loss. Results Despite extended donor warm ischaemia, HOPE-treated DCD liver transplants achieved similar overall graft survival, compared to standard DBD liver transplants. Particularly, graft loss due to any non-tumour-related causes occurred in 8% (4/50) of cases. In contrast, untreated DCD livers resulted in non-tumour-related graft failure in one-third (16/50) of cases (p = 0.005), despite significantly (p <0.001) shorter functional donor warm ischaemia. Five-year graft survival, censored for tumour death, was 94% for HOPE-treated DCD liver transplants vs. 78% in untreated DCD liver transplants (p = 0.024). Conclusions The 5-year outcomes of HOPE-treated DCD liver transplants were similar to those of DBD primary transplants and superior to those of untreated DCD liver transplants, despite much higher risk. These results suggest that a simple end-ischaemic perfusion approach is very effective and may open the field for safe utilisation of extended DCD liver grafts. Lay summary Machine perfusion techniques are currently being introduced into the clinic, with the aim of optimising injured grafts prior to implantation. While short-term effects of machine liver perfusion have been frequently reported in terms of hepatocellular enzyme release and early graft function, the long-term benefit on irreversible graft loss has been unclear. Herein, we report on 5-year graft survival in donation after cardiac death livers, treated either by conventional cold storage, or by 1–2 h of hypothermic oxygenated perfusion (HOPE) after cold storage. Graft loss was significantly less in HOPE-treated livers, despite longer donor warm ischaemia times. Therefore, HOPE after cold storage appears to be a simple and effective method to treat high-risk livers before implantation. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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49. Potentially inappropriate liver transplantation in the era of the “sickest first” policy – A search for the upper limits.
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Linecker, Michael, Krones, Tanja, Berg, Thomas, Niemann, Claus U., Steadman, Randolph H., Dutkowski, Philipp, Clavien, Pierre-Alain, Busuttil, Ronald W., Truog, Robert D., and Petrowsky, Henrik
- Subjects
- *
LIVER transplantation , *TRANSPLANTATION of organs, tissues, etc. , *LIVER disease treatment , *MORTALITY , *DECISION making in clinical medicine - Abstract
Summary Liver transplantation has emerged as a highly efficient treatment for a variety of acute and chronic liver diseases. However, organ shortage is becoming an increasing problem globally, limiting the applicability of liver transplantation. In addition, potential recipients are becoming sicker, thereby increasing the risk of losing the graft during transplantation or in the initial postoperative period after liver transplantation (three months). This trend is challenging the model for end-stage liver disease allocation system, where the sickest candidates are prioritised and no delisting criteria are given. The weighting of the deontological demand for “equity”, trying to save every patient, regardless of the overall utility; and “efficiency”, rooted in utilitarianism, trying to save as many patients as possible and increase the overall quality of life of patients facing the same problem, has to be reconsidered. In this article we are aiming to overcome the widespread concept of futility in liver transplantation, providing a definition of potentially inappropriate liver transplantation and giving guidance on situations where it is best not to proceed with liver transplantation, to decrease the mortality rate in the first three months after transplantation. We propose “absolute” and “relative” conditions, where early post-transplant mortality is highly probable, which are not usually captured in risk scores predicting post-transplant survival. Withholding liver transplantation for listed patients in cases where liver transplant is not deemed clearly futile, but is potentially inappropriate, is a far-reaching decision. Until now, this decision had to be discussed extensively on an individual basis, applying explicit communication and conflict resolution processes, since the model for end-stage liver disease score and most international allocation systems do not include explicit delisting criteria to support a fair delisting process. More work is needed to better identify cases where transplantation is potentially inappropriate and to integrate and discuss these delisting criteria in allocation systems, following a societal debate on what we owe to all liver transplant candidates. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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50. Hypothermic oxygenated perfusion (HOPE) for fatty liver grafts in rats and humans.
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Kron, Philipp, Schlegel, Andrea, Mancina, Leandro, Clavien, Pierre-Alain, and Dutkowski, Philipp
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- *
FATTY liver , *ISOLATION perfusion , *THERAPEUTICS , *FATTY liver prevention , *LIVER disease treatment - Abstract
Background & Aims Pretreatment of marginal organs by perfusion is a promising opportunity to make more organs available for transplantation. Protection of human donation after cardiac death (DCD) livers by a novel machine perfusion technique, hypothermic oxygenated perfusion (HOPE), was recently established. Herein, we tested whether HOPE is also useful for fatty liver grafts, using a rodent transplant model. Methods Rats were fed over three weeks with a special methionine-choline-deficient diet (MCDD) to induce severe hepatic macrosteatosis (≥60%). Afterwards, livers were transplanted with either minimal or 12 h cold storage. Additional liver grafts were treated after 12 h cold storage with 1 h HOPE before transplantation. Graft injury after orthotopic liver transplantation (OLT) was assessed in terms of oxidative stress, damage-associated molecular patterns release, toll-like receptor-4 activation, cytokine release, endothelial activation, and the development of necrosis and fibrosis. Results Implantation of cold stored macrosteatotic liver grafts induced massive reperfusion injury after OLT, compared to controls (non-fatty livers). HOPE treatment after cold storage failed to change the degree of steatosis itself, but markedly decreased reperfusion injury after OLT, as detected by less oxidative stress, less nuclear injury, less Kupffer- and endothelial cell activation, as well as less fibrosis within one week after OLT. Protective effects were lost in the absence of oxygen in the HOPE perfusate. Conclusion HOPE after cold storage of fatty livers prevents significant reperfusion injury and improves graft function, comparable to the effects of HOPE in DCD livers and DCD kidneys. HOPE treatment is easy and may become a universal concept to further expand the donor pool. Lay summary An increasing number of donor livers contain fat. It is important to harness marginal livers, which may contain fat, as the stock of donor livers is limited. Hypothermic oxygenated perfusion (HOPE) prevents reperfusion injury and improves liver graft function. HOPE offers a simple and low-cost option for treating liver grafts in transplant centers, even after cold storage, instead of transporting machines to the place of procurement. HOPE could be used globally to expand the donor pool. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
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