Regarding “Compared Efficacy of Preservation Solutions in Liver Transplantation: A Long-Term Graft Outcome Study From the European Liver Transplant Registry”

To the Editor: With great interest, we read the paper by Adam et al (1.Adam R Delvart V Karam V Compared efficacy of preservation solutions in liver transplantation: A long-term graft outcome study from the European Liver Transplant Registry.Am J Transplant. 2015; 15 (et al): 395-406Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar) analyzing the database of the European Liver Transplant Registry (ELTR) with regard to efficacy of different preservation solutions for preservation injury and graft survival after liver transplantation. This paper is noteworthy for its authentic reporting and thorough analysis. It is an important addition to the retrospective analysis of the United Network for Organ Sharing database by Stewart et al (2.Stewart ZA Cameron AM Singer AL Montgomery RA Segev DL. Histidine-tryptophan-ketoglutarate (HTK) is associated with reduced graft survival in deceased donor livers, especially those donated after cardiac death.Am J Transplant. 2009; 9: 286-293Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar). Not withstanding this powerful analysis, the results are highly controversial, especially in light of the current overhaul of the German transplant system. To date, prospective randomized trials have not been able to demonstrate different outcomes following the use of either perfusion solution (3.O’Callaghan JM Morgan RD Knight SR Morris PJ. The effect of preservation solutions for storage of liver allografts on transplant outcomes: A systematic review and meta-analysis.Ann Surg. 2014; 260: 46-55Crossref PubMed Scopus (38) Google Scholar). At the same time, registry data are subject to selection bias, even after careful correction for confounders (4.Schemmer P Fischer L Schmidt J Buchler MW. Intercontinental comparison of patient cohorts: What can we learn from it?.Gut. 2007; 56: 1500-1501Crossref PubMed Scopus (3) Google Scholar). The analysis by Adam et al, for example, presented a disparate portion of live liver donation between the study groups and a high proportion of incomplete data sets that were omitted from the survival analysis. Accordingly, we believe that this study has major flaws that should be addressed in sufficient detail. In the early 2000s, the Deutsche Stiftung Organtransplantation (German Organ Transplantation Foundation) introduced the exclusive use of histidine–tryptophan–ketoglutarate (HTK) solution for abdominal organ recovery due to safety and licensing concerns with University of Wisconsin (UW) solution. In particular, crystal formation clogging the flush-line filter, complicated cooling chain regulations, and repeated batch recalls by the European distributor had caused the depreciation of UW solution. This policy has been upheld ever since, and the vast majority of liver grafts recovered in Germany after 2004 were perfused with HTK solution. At the same time, cross-border exchange rates were low. Less than 15% of liver grafts transplanted annually in Germany were recovered abroad (mainly from countries cooperating through Eurotransplant, www.eurotransplant.org), whereas clearly <10% of grafts transplanted at ELTR centers outside Germany were recovered within Germany. Within the period of the analysis by Adam et al, approximately 9400 adult liver transplantations were performed at German transplant centers (5.Eurotransplant International Foundation. Annual reports. Available from: https://www.eurotransplant.org/cms/index.php?page=annual_reportsGoogle Scholar). Considering that all but three German transplant centers are registered with the ELTR, providing 98% of the liver transplantations (exceptions, according to the ELTR, are university medical centers at Aachen, Homburg, and Magdeburg), it appears likely that the majority of the 8696 HTK-preserved grafts analyzed by Adam et al were transplanted in Germany. At the same time, we have recognized that survival after liver transplantation has dropped significantly in Germany since 2006, after changing the allocation algorithm by implementation of the Model For End-Stage Liver Disease score (6.Weismuller TJ Fikatas P Schmidt J Multicentric evaluation of model for end-stage liver disease-based allocation and survival after liver transplantation in Germany–limitations of the ‘sickest first’-concept.Transpl Int. 2011; 24 (et al): 91-99Crossref PubMed Scopus (125) Google Scholar, 7.Schlitt HJ Loss M Scherer MN Current developments in liver transplantation in Germany: MELD-based organ allocation and incentives for transplant centres [in German].Z Gastroenterol. 2011; 49 (et al): 30-38Crossref PubMed Scopus (70) Google Scholar, 8.Weismuller TJ Negm A Becker T The introduction of MELD-based organ allocation impacts 3-month survival after liver transplantation by influencing pretransplant patient characteristics.Transpl Int. 2009; 22 (et al): 970-978Crossref PubMed Scopus (81) Google Scholar). In addition, several important risk factors for preservation injury and graft survival (e.g. donor graft steatosis, donor intensive care unit treatment) that might address varying national allocation policies were not considered by Adam et al. Consequently, we would like to raise for consideration whether German allocation policies significantly influenced the results presented by Adam et al rather than cold storage solutions, warranting additional analysis of the impact that German center data had on the overall outcome. Furthermore, we suggest an analysis of both demographic recipient and donor data excluding incomplete and live donation data sets. The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. P. Schemmer has received travel and research grants, and speaker fees from Dr. Franz Köhler Chemie GmbH (Bensheim, Germany). The other authors of this manuscript have no conflicts of interest to disclose.