Outcome of Liver Transplant Patients with High Urgent Priority
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Transplantation Direct Original Clinical Science—Liver TP Outcome of Liver Transplant Patients With High TPA Urgent Priority: Are We Doing the Right Thing? Jacob D. de Boer, MD,1,2 Andries E. Braat, MD, PhD,2 Hein Putter, PhD,3 Erwin de Vries, MSc,1 Christian H. 0041-1337/18/10306-1181 Strassburg, MD, PhD,4 Zoltán Máthé, MD, PhD,5 Bart van Hoek, MD, PhD,6 Felix Braun, MD, PhD,7 Aad P. van den Berg, MD, PhD,8 Danko Mikulic, MD, PhD,9 Peter Michielsen, MD, PhD,10 Blaz Trotovsek, MD, 2373-8731 PhD,11 Heinz Zoller, MD, PhD,12 Jan de Boer, MD,1 Marieke D. van Rosmalen, MD,1 Undine Samuel, MD, 13 14 15 Lippincott Williams & WilkinsHagerstown, MD PhD, Gabriela Berlakovich, MD, and Markus Guba, MD, PhD ; on behalf of the Eurotransplant Liver and Intestine Advisory Committee (ELIAC) 10.1097/TP.0000000000002526 Background. About 15% of liver transplantations (LTs) in Eurotransplant are currently performed in patients with a high- de Boer et al urgency (HU) status. Patients who have acute liver failure (ALF) or require an acute retransplantation can apply for this status. This study aims to evaluate the efficacy of this prioritization.Methods. Patients who were listed for LT with HU xxxJune status from January 1, 2007, up to December 31, 2015, were included. Waiting list and posttransplantation outcomes were evaluated and compared with a reference group of patients with laboratory Model for End-Stage Liver Disease xxxMonth2019 (MELD) score (labMELD) scores ≥40 (MELD 40+). Results. In the study period, 2299 HU patients were listed for LT. Ten days after listing, 72% of all HU patients were transplanted and 14% of patients deceased. Patients with HU status 6 for primary ALF showed better patient survival at 3 years (69%) when compared with patients in the MELD 40+ group 2019 (57%). HU patients with labMELD ≥45 and patients with HU status for acute retransplantation and labMELD ≥35 have significantly inferior survival at 3-year follow-up of 46% and 42%, respectively. Conclusions. Current prioritization for patients with ALF is highly effective in preventing mortality on the waiting list. Although patients with HU status for ALF have good outcomes, survival is significantly inferior for patients with a high MELD score or for retransplantations. With the current scarcity of livers in mind, we should discuss whether potential recipients for a second or even third retrans- plantation should still receive absolute priority, with HU status, over other recipients with an expected, substantially better prognosis after transplantation. (Transplantation 2019;103:1181–1190) Received 12 July 2018. Revision received 2 October 2018. 12 Klinik für Innere Medizin II–Hepatologie, Tirol Kliniken GmbH, Innsbruck, Austria. Accepted 29 October 2018. 13 Eurotransplant International Foundation, Leiden, The Netherlands. 1 14 Eurotransplant International Foundation, Leiden, The Netherlands. Division of Transplantation, Department of Surgery, Medical University of 2 Vienna, Austria. Division of Transplantation, Department of Surgery, Leiden University Medical 15 Center, Leiden, The Netherlands. Department of General-, Visceral-, and Transplant Surgery, University of Munich, Munich, Germany. 3 Department of Biomedical Data Sciences, Leiden University Medical Center, The authors declare no funding or conflicts of interest. Leiden, The Netherlands. J.D.d.B., A.v.d.B., A.B., and M.G. conceptualized and designed the study. Jan de 4 Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik, Bonn, Boer, M.v.R., E.d.V., C.H.S., Z.M., B.v.H., F.B., D.M., P.M., B.T., G.B., and M.G. Germany. acquired the data. Jacob de Boer, E.d.V., and H.P. statistically analyzed the data. 5 Department of Transplantation and Surgery, Semmelweis Medical University, Jacob de Boer, E.d.V., A.B., A.v.d.B., G.B., and M.G. analyzed and interpreted the Budapest, Hungary. data. Jacob de Boer, U.S., A.B., A.v.d.B., and M.G. drafted the manuscript. Jacob 6 Department of Gastroenterology and Hepatology, Leiden University Medical de Boer, M.G., A.B., H.P., A.v.d.B., E.d.V., C.H.S., Z.M., B.v.H., F.B., D.M., P.M., B.T., G.B., H.Z., J.d.B., M.v.R., and U.S. critically revised the manuscript. U.S., Center, Leiden, The Netherlands. A.B., and M.G. supervised the study. 7 Klinik fur Allgemeine, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Correspondence: Jacob de Boer, MD, Eurotransplant International Foundation, Universitätsklinikum Schleswig-Holstein Campus Kiel, Kiel, Germany. P.O. Box 2304, NL - 2301 CH Leiden, The Netherlands. (jacob.deboer@ 8 Department of Gastroenterology, University Medical Center Groningen, eurotransplant.org). Groningen, The Netherlands. Supplemental digital content (SDC) is available for this article. Direct URL cita- 9 Department of Surgery, Clinical Hospital Merkur, Zagreb, Croatia. tions appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com). 10 Department of Gastroenterology and Hepatology, University Hospital Antwerp, Antwerpen, Belgium. © 2019 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc. 11 Department of Abdominal Surgery, University Medical Center Ljubljana, ISSN: 0041-1337/18/10306-1181 Ljubljana, Slovenia. DOI: 10.1097/TP.0000000000002526 Transplantation ■ June 2019 ■ Volume 103 ■ Number 6 www.transplantjournal.com 1181 Copyright © 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. <zdoi;10.1097/TP.0000000000002526> LWW 1182 Transplantation ■ June 2019 ■ Volume 103 ■ Number 6 www.transplantjournal.com INTRODUCTION antibodies (HCVAb) status, hepatitis B antibodies status, Patients who present with acute liver failure (ALF) have type of donation (donation after determination of circu- a high risk of mortality because no bridging options are latory death [DCD]/donation after brain death [DBD]), available for severe liver dysfunction. With the introduc- cause of death, body mass index (BMI), history of diabetes tion of liver transplantation (LT), their chances for survival (y/n), and recipient information on age at delisting, cause have increased significantly.1,2 of liver disease, BMI, HCVAb status, number of previous To increase the chance of a timely, suitable donor liver, 8 LTs, labMELD category, sex, split (y/n), allocation region countries in Europe cooperate within Eurotransplant. This (local, regional, extraregional), simultaneous liver and kid- cooperation covers Germany, The Netherlands, Belgium, ney, rescue allocation, and total ischemic time. Austria, Croatia, Luxemburg, Hungary, and Slovenia and Data were checked for outliers and were set at missing or has a total population of around 136 million inhabit- corrected when appropriate (length/weight switch). Recipient ants. Patients from these countries with primary ALF and BMI was missing for 1 patient, and donor last GGT was patients who require an acute retransplantation (<14 days) missing for 58 donors (0.02%). For both recipient BMI and can apply for a high-urgency (HU) status.3 The HU status donor last GGT, median values were imputed as 25.4 kg/m2 gives the patient international priority within all participat- and 32 U/L, respectively. Total ischemic time was defined as ing countries. When a suitable organ becomes available, HU time between starting time of cold perfusion of the aorta in patients are the first to receive an offer for that organ, cross- the donor and time of reperfusion in the recipient. In case border.3,4 Patients can receive this status when they fulfill of missing values (27 transplantations, 0.01%), median value standard criteria or when accepted by an individual audit of 8.35 hours was imputed. Donor hepatitis B antibodies, of 2 members of the Eurotransplant Liver and Intestine HCVAb, and recipient HCVAb were considered as present Advisory Committee (ELIAC) (Definitions; Methods).3 when Yes and not present when otherwise. Primary ALF Over the last years (2012–2016), about 15% of all LTs diagnoses were categorized as Budd-Chiari, viral hepatitis, within Eurotransplant were performed in patients with an toxin/drug induced, Wilson’s disease, paracetamol, and other. HU status.5 HU status prioritization is currently consid- Viral hepatitis comprised hepatitis A, B, C, D, E; cytomeg- ered justified because these patients are at imminent risk of alovirus; herpes simplex virus; and other unspecified viruses. death. It is primarily based on the urgency for LT, but to date, The category “Other” comprised causes as autoimmune dis- outcome of this allocation mode has been disregarded. The eases, postoperative liver failure, (liver) trauma, anhepatic group of patients with HU status is heterogeneous, and there state, Osler’s disease, Still’s disease, Weil’s disease, pregnancy- might be a (sub)group of patients with very poor prognosis related illnesses, and α-1-antitrypsin deficiency. Causes for even in case of an urgent LT. These HU patients are currently acute retransplantations were categorized as hepatic artery transplanted with priority over other critically ill patients thrombosis (HAT), biliary tract necrosis, portal vein throm- who face the risk of dying while on the waiting list, although bosis, primary nonfunction (PNF), and other. The other cate- they might have a significantly higher chance of survival. gory comprised acute cellular rejections, transmitted tumor in This study aims to evaluate the efficacy of the HU status a recently transplanted liver, infected biliomas, other unspeci- on waiting list outcome. Then, outcome after LT is ana- fied complications of the operation, rupture of a mycotic lyzed for transplanted HU patients to identify high-risk aneurysm, sinusoidal obstruction syndrome, ruptured and patients. These outcomes are compared with a reference bad perfused organs, risk of tumor transmission, liver necro- group of patients without HU status but with a Model for sis, and compartment syndrome due to bleeding. End-Stage Liver Disease (MELD) score of ≥40. For all transplantations, the Eurotransplant-Donor Risk Index,6 simplified Recipient Risk Index,7 and Donor and 7 METHODS Recipient Model were calculated.