Prädiktoren für erfolgreiche Lebertransplantationen und Risikofaktoren

Zusammenfassung

Die Lebertransplantation ist die einzige kurative Therapieoption einer chronischen Leberinsuffizienz im Endstadium. Daneben stellen onkologische Lebererkrankungen wie das HCC eine weitere Indikation für die Lebertransplantation dar, ebenso wie das akute Leberversagen.

Seit der ersten erfolgreichen Lebertransplantation durch Professor Thomas E. Starzl im Jahr 1967 haben sich nicht nur die chirurgischen, immunologischen und anästhesiologischen Techniken und Möglichkeiten geändert, sondern auch die Indikationen und das Patientengut. Hinzu kommt, dass die Empfänger ein zunehmendes Lebensalter und damit einhergehend mehr Begleiterkrankungen aufweisen.

Die Zahl an Lebertransplantationen ist weltweit weiter ansteigend. Es benötigen aber mehr Menschen eine Lebertransplantation, als Organe zur Verfügung stehen. Dies liegt am zunehmenden Bedarf an Spenderorganen bei gleichzeitig weiter rückläufiger Zahl postmortaler Organspenden.

Diese Diskrepanz zwischen Spenderorganen und Empfängern kann nur zu einem kleinen Teil durch Split-Lebertransplantationen oder die Leberlebendspende kompensiert werden.

Um den Spenderpool zu erweitern, werden zunehmend auch marginale Organe, die nur die erweiterten Spenderkriterien („extended donor criteria [EDC]“) erfüllen, allokiert. In manchen Ländern zählen hierzu auch die sogenannten DCD-Organe (DCD: „donation after cardiac death“), d. h. Organe, die erst nach dem kardiozirkulatorischen Tod des Spenders entnommen werden.

Es ist bekannt, dass marginale Spenderorgane mit einem erhöhten Risiko für ein schlechteres Transplantat- und Patientenüberleben nach Lebertransplantation einhergehen.

Um die Qualität marginaler Spenderorgane zu verbessern, hat sich eine rasante Entwicklung der Techniken der Organkonservierung über die letzten Jahre gezeigt. Mit der maschinellen Organperfusion besteht beispielsweise die Möglichkeit, die Organqualität deutlich zu verbessern. Insgesamt haben sich die Risikokonstellationen von Spenderorgan und Transplantatempfänger deutlich geändert.

Aus diesem Grunde ist es von großer Bedeutung, spezifische Prädiktoren für eine erfolgreiche Lebertransplantation sowie die entsprechenden Risikofaktoren für einen schlechten postoperativen Verlauf zu kennen, um das bestmögliche Transplantat- und Patientenüberleben nach Lebertransplantation zu ermöglichen.

Diese Einflussfaktoren, inklusive möglicher Risiko-Scores, sollen hier ebenso wie die neuen technischen Möglichkeiten in der Lebertransplantation beleuchtet werden.

Abstract

Liver transplantation is the only curative treatment option for end stage liver disease. Moreover, oncological liver disease (hepatocellular carcinoma) is an important relevant indication for liver transplantation, together with acute liver failure.

Since the first successful liver transplantation by Professor Thomas Starzl in 1967, liver transplantation has changed in many aspects. This concerns not only surgical, anaesthesiological and immunological improvements and further technical developments, but also altered patient characteristics. Patients undergoing liver transplantation are nowadays often more challenging, due to their age and relevant comorbidities.

The number of liver transplantations is constantly rising. However, there are more patients in need of liver transplantation than donor grafts are available. Discrepancies between liver transplant candidates and organ supply can only partially be compensated by split liver transplantation and liver transplantation from living donors.

To boost the pool of donor grafts, even marginal organs within the extended donor criteria (EDC) are being increasingly allocated. In some countries, even “donation after cardiac death (DCD) organs” are allocated as well.

Marginal donor grafts are often associated with reduced graft and patient survival after liver transplantation. To improve the quality of poor liver grafts, innovations in organ conservation with development of new techniques as the machine perfusion techniques have been established in recent years.

In summary, the constellation of risk factors of donor grafts as well as transplant recipients has become more challenging in recent decades. It is important to know the specific risk factors and predictors for liver transplantation, in order to obtain the best possible graft and patient survival after liver transplantation.

This review gives an overview of predictors for liver transplantation, specific risk scores and indices for donor/recipient match as well as new technical devices in liver transplantation.

Schlüsselwörter

Leberchirurgie - Leberversagen - Risikofaktor - Transplantation

Keywords

liver failure - liver surgery - risk factor - transplantation surgery

Publication History

Received: 23 March 2022

Accepted after revision: 26 May 2022

Article published online:
21 July 2022

• Literatur

• 1 Manns M, Samuel D, Gane EJ. et al. Ledipasvir and sofosbuvir plus ribavirin in patients with genotype 1 or 4 hepatitis C virus infection and advanced liver disease: a multicentre, open-label, randomised, phase 2 trial. Lancet Infect Dis 2016; 16: 685-697 DOI: 10.1016/S1473-3099(16)00052-9. (PMID: 26907736)
• 2 Cotter TG, Charlton M. Nonalcoholic Steatohepatitis After Liver Transplantation. Liver Transpl 2020; 26: 141-159 DOI: 10.1002/lt.25657. (PMID: 31610081)
• 3 Adam R, Karam V, Cailliez V. et al. 2018 Annual Report of the European Liver Transplant Registry (ELTR) – 50-year evolution of liver transplantation. Transpl Int 2018; 31: 1293-1317 DOI: 10.1111/tri.13358. (PMID: 30259574)
• 4 Calzadilla Bertot L, Adams LA. The Natural Course of Non-Alcoholic Fatty Liver Disease. Int J Mol Sci 2016; 17: 774 DOI: 10.3390/ijms17050774. (PMID: 27213358)
• 5 Allemani C, Matsuda T, Di Carlo V. et al. Global surveillance of trends in cancer survival 2000–14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet 2018; 391: 1023-1075 DOI: 10.1016/S0140-6736(17)33326-3. (PMID: 29395269)
• 6 Durand F, Levitsky J, Cauchy F. et al. Age and liver transplantation. J Hepatol 2019; 70: 745-758 DOI: 10.1016/j.jhep.2018.12.009. (PMID: 30576701)
• 7 Shaw jr. BW. Transplantation in the elderly patient. Surg Clin North Am 1994; 74: 389-400 (PMID: 8165474)
• 8 Schwartz JJ, Pappas L, Thiesset HF. et al. Liver transplantation in septuagenarians receiving model for end-stage liver disease exception points for hepatocellular carcinoma: the national experience. Liver Transpl 2012; 18: 423-433 DOI: 10.1002/lt.23385. (PMID: 22250078)
• 9 Bilbao I, Dopazo C, Lazaro JL. et al. Our experience in liver transplantation in patients over 65 yr of age. Clin Transplant 2008; 22: 82-88 DOI: 10.1111/j.1399-0012.2007.00749.x. (PMID: 18251043)
• 10 Nagai S, Collins K, Chau LC. et al. Increased Risk of Death in First Year After Liver Transplantation Among Patients With Nonalcoholic Steatohepatitis vs Liver Disease of Other Etiologies. Clin Gastroenterol Hepatol 2019; 17: 2759-2768 e2755 DOI: 10.1016/j.cgh.2019.04.033. (PMID: 31004758)
• 11 Thoefner LB, Rostved AA, Pommergaard HC. et al. Risk factors for metabolic syndrome after liver transplantation: A systematic review and meta-analysis. Transplant Rev (Orlando) 2018; 32: 69-77 DOI: 10.1016/j.trre.2017.03.004. (PMID: 28501338)
• 12 Zhou J, Zhang X, Lyu L. et al. Modifiable risk factors of acute kidney injury after liver transplantation: a systematic review and meta-analysis. BMC Nephrol 2021; 22: 149 DOI: 10.1186/s12882-021-02360-8. (PMID: 33888081)
• 13 Baliga P, Merion RM, Turcotte JG. et al. Preoperative risk factor assessment in liver transplantation. Surgery 1992; 112: 704-710 (PMID: 1411941)
• 14 Feng S, Goodrich NP, Bragg-Gresham JL. et al. Characteristics associated with liver graft failure: the concept of a donor risk index. Am J Transplant 2006; 6: 783-790 DOI: 10.1111/j.1600-6143.2006.01242.x. (PMID: 16539636)
• 15 Jay CL, Lyuksemburg V, Ladner DP. et al. Ischemic cholangiopathy after controlled donation after cardiac death liver transplantation: a meta-analysis. Ann Surg 2011; 253: 259-264 DOI: 10.1097/SLA.0b013e318204e658. (PMID: 21245668)
• 16 Hoofnagle JH, Lombardero M, Zetterman RK. et al. Donor age and outcome of liver transplantation. Hepatology 1996; 24: 89-96 DOI: 10.1002/hep.510240116. (PMID: 8707288)
• 17 Berenguer M, Prieto M, San Juan F. et al. Contribution of donor age to the recent decrease in patient survival among HCV-infected liver transplant recipients. Hepatology 2002; 36: 202-210 DOI: 10.1053/jhep.2002.33993.
• 18 Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 2002; 287: 356-359 DOI: 10.1001/jama.287.3.356. (PMID: 11790215)
• 19 Pratschke S, Bender A, Boesch F. et al. Association between donor age and risk of graft failure after liver transplantation: an analysis of the Eurotransplant database. Transpl Int 2019; 32: 270-279 DOI: 10.1111/tri.13357. (PMID: 30260509)
• 20 Aloia TA, Knight R, Gaber AO. et al. Analysis of liver transplant outcomes for United Network for Organ Sharing recipients 60 years old or older identifies multiple model for end-stage liver disease-independent prognostic factors. Liver Transpl 2010; 16: 950-959 DOI: 10.1002/lt.22098. (PMID: 20589647)
• 21 Dutkowski P, Schlegel A, Slankamenac K. et al. The use of fatty liver grafts in modern allocation systems: risk assessment by the balance of risk (BAR) score. Ann Surg 2012; 256: 861-868 DOI: 10.1097/SLA.0b013e318272dea2. (PMID: 23095632)
• 22 Andert A, Ulmer TF, Schoning W. et al. Grade of donor liver microvesicular steatosis does not affect the postoperative outcome after liver transplantation. Hepatobiliary Pancreat Dis Int 2017; 16: 617-623 DOI: 10.1016/S1499-3872(17)60064-X. (PMID: 29291781)
• 23 Han S, Ko JS, Kwon G. et al. Effect of pure microsteatosis on transplant outcomes after living donor liver transplantation: a matched case-control study. Liver Transpl 2014; 20: 473-482 DOI: 10.1002/lt.23824. (PMID: 24425681)
• 24 Croome KP, Lee DD, Croome S. et al. The impact of postreperfusion syndrome during liver transplantation using livers with significant macrosteatosis. Am J Transplant 2019; 19: 2550-2559 DOI: 10.1111/ajt.15330. (PMID: 30821923)
• 25 Doyle MB, Vachharajani N, Wellen JR. et al. Short- and long-term outcomes after steatotic liver transplantation. Arch Surg 2010; 145: 653-660 DOI: 10.1001/archsurg.2010.119. (PMID: 20644128)
• 26 Croome KP, Lee DD, Perry DK. et al. Comparison of longterm outcomes and quality of life in recipients of donation after cardiac death liver grafts with a propensity-matched cohort. Liver Transpl 2017; 23: 342-351 DOI: 10.1002/lt.24713. (PMID: 28027600)
• 27 Schlegel A, Muiesan P. Can we minimize wait-list mortality in young children with Biliary atresia?. Liver Transpl 2018; 24: 731-732 DOI: 10.1002/lt.25190. (PMID: 29704300)
• 28 Walcott J, Fink M, Ealing I. et al. Procurement-related liver injury for transplantation: an analysis of the risk factors and consequences in an Australian transplant centre. ANZ J Surg 2021; 91: 2669-2674 DOI: 10.1111/ans.17285. (PMID: 34723420)
• 29 Addeo P, Schaaf C, Noblet V. et al. The learning curve for piggyback liver transplantation: identifying factors challenging surgery. Surgery 2021; 169: 974-982 DOI: 10.1016/j.surg.2020.09.036. (PMID: 33143932)
• 30 Domagala P, Takagi K, Porte RJ. et al. Order of liver graft revascularization in deceased liver transplantation: A systematic review and meta-analysis. Surgery 2019; 166: 237-246 DOI: 10.1016/j.surg.2019.03.024. (PMID: 31085045)
• 31 Pinto LEV, Coelho GR, Coutinho MMS. et al. Risk Factors Associated with Hepatic Artery Thrombosis: Analysis of 1050 Liver Transplants. Arq Bras Cir Dig 2021; 33: e1556 DOI: 10.1590/0102-672020200004e1556. (PMID: 33503116)
• 32 Buchholz BM, Gerlach UA, Chandrabalan VV. et al. Revascularization Time in Liver Transplantation: Independent Prediction of Inferior Short- and Long-term Outcomes by Prolonged Graft Implantation. Transplantation 2018; 102: 2038-2055 DOI: 10.1097/TP.0000000000002263. (PMID: 29757901)
• 33 Hackl C, Schmidt KM, Susal C. et al. Split liver transplantation: Current developments. World J Gastroenterol 2018; 24: 5312-5321 DOI: 10.3748/wjg.v24.i47.5312. (PMID: 30598576)
• 34 Boillot O, Delafosse B, Mechet I. et al. Small-for-size partial liver graft in an adult recipient; a new transplant technique. Lancet 2002; 359: 406-407 DOI: 10.1016/S0140-6736(02)07593-1. (PMID: 11844516)
• 35 Reyes J, Perkins J, Kling C. et al. Size mismatch in deceased donor liver transplantation and its impact on graft survival. Clin Transplant 2019; 33: e13662 DOI: 10.1111/ctr.13662. (PMID: 31283049)
• 36 Masuda Y, Yoshizawa K, Ohno Y. et al. Small-for-size syndrome in liver transplantation: Definition, pathophysiology and management. Hepatobiliary Pancreat Dis Int 2020; 19: 334-341 DOI: 10.1016/j.hbpd.2020.06.015. (PMID: 32646775)
• 37 Yan Y, Zheng DF, Pu JL. et al. Outcomes of adult patients adopting small-for-size grafts in living donor liver transplantation: A systematic review and meta-analysis. Hepatobiliary Pancreat Dis Int 2019; 18: 206-213 DOI: 10.1016/j.hbpd.2019.03.007. (PMID: 30952435)
• 38 Ivanics T, Abreu P, De Martin E. et al. Changing Trends in Liver Transplantation: Challenges and Solutions. Transplantation 2021; 105: 743-756 DOI: 10.1097/TP.0000000000003454. (PMID: 32910093)
• 39 Ravikumar R, Jassem W, Mergental H. et al. Liver Transplantation After Ex Vivo Normothermic Machine Preservation: A Phase 1 (First-in-Man) Clinical Trial. Am J Transplant 2016; 16: 1779-1787 DOI: 10.1111/ajt.13708. (PMID: 26752191)
• 40 Nasralla D, Coussios CC, Mergental H. et al. A randomized trial of normothermic preservation in liver transplantation. Nature 2018; 557: 50-56 DOI: 10.1038/s41586-018-0047-9. (PMID: 29670285)
• 41 Bral M, Dajani K, Leon Izquierdo D. et al. A Back-to-Base Experience of Human Normothermic Ex Situ Liver Perfusion: Does the Chill Kill?. Liver Transpl 2019; 25: 848-858 DOI: 10.1002/lt.25464. (PMID: 30938039)
• 42 Laing RW, Mergental H, Yap C. et al. Viability testing and transplantation of marginal livers (VITTAL) using normothermic machine perfusion: study protocol for an open-label, non-randomised, prospective, single-arm trial. BMJ Open 2017; 7: e017733 DOI: 10.1136/bmjopen-2017-017733. (PMID: 29183928)
• 43 Dondossola D, Lonati C, Zanella A. et al. Preliminary Experience With Hypothermic Oxygenated Machine Perfusion in an Italian Liver Transplant Center. Transplant Proc 2019; 51: 111-116 DOI: 10.1016/j.transproceed.2018.04.070. (PMID: 30736971)
• 44 Schlegel A, Muller X, Kalisvaart M. et al. Outcomes of DCD liver transplantation using organs treated by hypothermic oxygenated perfusion before implantation. J Hepatol 2019; 70: 50-57 DOI: 10.1016/j.jhep.2018.10.005. (PMID: 30342115)
• 45 Quillin 3rd RC, Guarrera JV. Hypothermic machine perfusion in liver transplantation. Liver Transpl 2018; 24: 276-281 DOI: 10.1002/lt.25004. (PMID: 29278454)
• 46 Kron P, Schlegel A, Mancina L. et al. Hypothermic oxygenated perfusion (HOPE) for fatty liver grafts in rats and humans. J Hepatol 2017; DOI: 10.1016/j.jhep.2017.08.028. (PMID: 28870676)
• 47 de Vries Y, Berendsen TA, Fujiyoshi M. et al. Transplantation of high-risk donor livers after resuscitation and viability assessment using a combined protocol of oxygenated hypothermic, rewarming and normothermic machine perfusion: study protocol for a prospective, single-arm study (DHOPE-COR-NMP trial). BMJ Open 2019; 9: e028596 DOI: 10.1136/bmjopen-2018-028596. (PMID: 31420387)
• 48 Asrani SK, Kim WR, Edwards EB. et al. Impact of the center on graft failure after liver transplantation. Liver Transpl 2013; 19: 957-964 DOI: 10.1002/lt.23685. (PMID: 23784730)
• 49 Wong NZ, Schaubel DE, Reddy KR. et al. Transplant center experience influences spontaneous survival and waitlist mortality in acute liver failure: An analysis of the UNOS database. Am J Transplant 2021; 21: 1092-1099 DOI: 10.1111/ajt.16234. (PMID: 32741074)
• 50 Loosen SH, Bock HH, Hellmich M. et al. Hospital Mortality and Current Trends in Liver Transplantation in Germany-a Systematic Analysis of Standardized Hospital Discharge Data, 2008–2017. Dtsch Arztebl Int 2021; 118: 497-502 DOI: 10.3238/arztebl.m2021.0210. (PMID: 33888199)
• 51 Flores A, Asrani SK. The donor risk index: A decade of experience. Liver Transpl 2017; 23: 1216-1225 DOI: 10.1002/lt.24799. (PMID: 28590542)
• 52 Briceno J, Ayllon MD, Ciria R. Machine-learning algorithms for predicting results in liver transplantation: the problem of donor-recipient matching. Curr Opin Organ Transplant 2020; 25: 406-411 DOI: 10.1097/MOT.0000000000000781. (PMID: 32487891)
• 53 Wiesner RH, McDiarmid SV, Kamath PS. et al. MELD and PELD: application of survival models to liver allocation. Liver Transpl 2001; 7: 567-580 DOI: 10.1053/jlts.2001.25879. (PMID: 11460223)
• 54 Blok JJ, Braat AE, Adam R. et al. Validation of the donor risk index in orthotopic liver transplantation within the Eurotransplant region. Liver Transpl 2012; 18: 112-119 DOI: 10.1002/lt.22447. (PMID: 21987454)
• 55 Goldberg DS, French B, Abt PL. et al. Superior survival using living donors and donor-recipient matching using a novel living donor risk index. Hepatology 2014; 60: 1717-1726 DOI: 10.1002/hep.27307. (PMID: 25042283)
• 56 Dutkowski P, Oberkofler CE, Slankamenac K. et al. 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. Ann Surg 2011; 254: 745-753 DOI: 10.1097/SLA.0b013e3182365081. (PMID: 22042468)
• 57 Rana A, Hardy MA, Halazun KJ. et al. Survival outcomes following liver transplantation (SOFT) score: a novel method to predict patient survival following liver transplantation. Am J Transplant 2008; 8: 2537-2546 DOI: 10.1111/j.1600-6143.2008.02400.x. (PMID: 18945283)
• 58 Ruf AE, Kremers WK, Chavez LL. et al. Addition of serum sodium into the MELD score predicts waiting list mortality better than MELD alone. Liver Transpl 2005; 11: 336-343 DOI: 10.1002/lt.20329. (PMID: 15719386)
• 59 Barber K, Madden S, Allen J. et al. Elective liver transplant list mortality: development of a United Kingdom end-stage liver disease score. Transplantation 2011; 92: 469-476 DOI: 10.1097/TP.0b013e318225db4d. (PMID: 21775931)
• 60 Artru F, Samuel D. Approaches for patients with very high MELD scores. JHEP Rep 2019; 1: 53-65 DOI: 10.1016/j.jhepr.2019.02.008. (PMID: 32039352)
• 61 Wiesner RH, Demetris AJ, Belle SH. et al. Acute hepatic allograft rejection: incidence, risk factors, and impact on outcome. Hepatology 1998; 28: 638-645 DOI: 10.1002/hep.510280306. (PMID: 9731552)
• 62 Dogan N, Husing-Kabar A, Schmidt HH. et al. Acute allograft rejection in liver transplant recipients: Incidence, risk factors, treatment success, and impact on graft failure. J Int Med Res 2018; 46: 3979-3990 DOI: 10.1177/0300060518785543. (PMID: 29996675)
• 63 Lee EC, Kim SH, Park SJ. Outcomes after liver transplantation in accordance with ABO compatibility: A systematic review and meta-analysis. World J Gastroenterol 2017; 23: 6516-6533 DOI: 10.3748/wjg.v23.i35.6516. (PMID: 29085201)
• 64 Charlton M, Levitsky J, Aqel B. et al. International Liver Transplantation Society Consensus Statement on Immunosuppression in Liver Transplant Recipients. Transplantation 2018; 102: 727-743 DOI: 10.1097/TP.0000000000002147. (PMID: 29485508)
• 65 De Simone P, Nevens F, De Carlis L. et al. Everolimus with reduced tacrolimus improves renal function in de novo liver transplant recipients: a randomized controlled trial. Am J Transplant 2012; 12: 3008-3020 DOI: 10.1111/j.1600-6143.2012.04212.x. (PMID: 22882750)
• 66 Campsen J, Zimmerman MA, Mandell S. et al. A Decade of Experience Using mTor Inhibitors in Liver Transplantation. J Transplant 2011; 2011: 913094 DOI: 10.1155/2011/913094. (PMID: 21461386)
• 67 Haddad EM, McAlister VC, Renouf E. et al. Cyclosporin versus tacrolimus for liver transplanted patients. Cochrane Database Syst Rev 2006; (04) CD005161 DOI: 10.1002/14651858.CD005161.pub2. (PMID: 17054241)
• 68 Evans MD, Diaz J, Adamusiak AM. et al. Predictors of Survival After Liver Transplantation in Patients With the Highest Acuity (MELD >/= 40). Ann Surg 2020; 272: 458-466 DOI: 10.1097/SLA.0000000000004211. (PMID: 32740239)
• 69 Amin A, Molina A, Quach L. et al. Liver Transplantation in Patients With Pretransplant Aspergillus Colonization: Is It Safe to Proceed?. Transplantation 2021; 105: 586-592 DOI: 10.1097/TP.0000000000003276. (PMID: 32301905)
• 70 Lerut J, Reding R, de Ville de Goyet J. et al. Technical problems in shipped hepatic allografts: the UCL experience. Transpl Int 1994; 7: 297-301 DOI: 10.1007/BF00327160. (PMID: 7916932)