Since the first clinical liver transplants were performed by Starzl at the University of Colorado in 1963,1 there have been several watershed moments in the field, beyond which liver transplantation has transformed:
- - A definition of irreversible coma was provided by the Ad Hoc Committee at Harvard Medical School in 1968 setting the stage for the recovery of organs from donation after brain death donors, with the donor heart still beating;2
- - Cyclosporine was introduced by Calne at the University of Cambridge/Kings College in the late 1970s.3 Its clinical application offered hither too unparalleled improvement in posttransplant survival that liver transplantation passed from the realm of experimental surgery to that of routine clinical practice. This was followed by the establishment of numerous programs and exponential expansion in the number of liver transplants performed worldwide;
- - Static cold storage with University of Wisconsin solution was introduced in late 1980s4,5 and remains the basis of organ preservation and the standard against which all other forms of preservation are currently compared;
- - Living donor liver transplantation was started for children in 19896 and adults in the 1990s7,8 and has allowed for the treatment of thousands of additional patients with end-stage liver disease and liver tumors, in particular in countries where deceased donation is limited.
Today, there is the potential of another watershed moment that will define the future of the field of liver transplantation. This watershed, however, involves reevaluating the origins of deceased organ donation where oxygenated blood circulation has ceased, representing a return to the very earliest days of deceased organ transplantation.
Out of necessity, donation after circulatory death (DCD) donors, the same donors from which the first livers for human transplantation were procured, have progressively moved from the realm of “niche” to the mainstream. Tagging on the heels of marginal DCD livers is perfusion preservation—first studied in the 1920s,9,10 applied when clinical transplant activity began in the 1960s,11,12 largely abandoned with the rise of donation after brain death and “modern” static cold preservation solutions, and finally resurrected by perseverant surgeon-scientists over the course of the past 2 decades to recondition and study and ultimately recover more marginal liver grafts.
In recognition of this growing importance of DCD and liver perfusion, the International Liver Transplantation Society (ILTS) in early 2019 tasked the Special Interest Group on DCD, Liver Preservation and Machine Perfusion to create working groups to perform systematic literature reviews and create a set of consensus statements to help guide clinicians and scientists working in liver DCD, preservation, and perfusion. The working groups were comprised of a total of 41 experts (38 surgeons, 1 hepatologist, 1 intensivist, and 1 nephrologist) and were tasked with addressing the following topics:
- - Donor warm ischemia times in DCD;
- - Liver donor and recipient selection and risk prediction in DCD;
- - Liver early allograft dysfunction and complications in DCD;
- - Regulations and liver procurement surgery in DCD;
- - Role and types of liver machine perfusion;
- - Clinical trial design in liver machine perfusion.
The groups worked on literature review and drafting of initial statements. A total of 151 professionals from 25 countries met on January 31, 2020, at the San Servolo Convention Center in Venice, Italy, to review and discuss the topics and statements. Despite the worst global pandemic in a century, the ILTS consensus statements were developed and finalized during 2020. Statements were classified according to the GRADE system,13 which reflects both the level of supporting evidence and the strength of the recommendations based on the degree of agreement among experts. After external review, the final results of this work are now being published in sequential issues of Transplantation, the first of which is published in this issue.14
As a final comment, we want to make special mention of the fact that these ILTS Consensus Statements are not only the fruit of over a year of international collaboration but also pay homage to our predecessors who persevered over the course of almost 6 decades to allow DCD and organ perfusion to provide an expanded future for liver transplantation.
1. Starzl TE, Marchioro TL, Vonkaulla KN, et al. Homotransplantation of the liver in humans. Surg Gynecol Obstet. 1963; 117:659–676
2. A definition of irreversible Coma. JAMA. 1968; 205:337–340
3. Calne RY, Rolles K, White DJ, et al. Cyclosporin A initially as the only immunosuppressant in 34 recipients of cadaveric organs: 32 kidneys, 2 pancreases, and 2 livers. Lancet. 1979; 2:1033–1036
4. Yoglu M, Stratta R, Hoffmann R, et al. Extended preservation of the liver for clinical transplantation. Lancet. 1988; 331:617–619
5. Todo S, Nery J, Yanaga K, et al. Extended preservation of human liver grafts with UW solution. JAMA. 1989; 261:711–714
6. Strong RW, Lynch SV, Ong TH, et al. Successful liver transplantation from a living donor to her son. N Engl J Med. 1990; 322:1505–1507
7. Yamaoka Y, Washida M, Honda K, et al. Liver transplantation using a right lobe graft from a living related donor. Transplantation. 1994; 57:1127–1130
8. Wachs ME, Bak TE, Karrer FM, et al. Adult living donor liver transplantation using a right hepatic lobe. Transplantation. 1998; 66:1313–1316
9. Verney EB, Starling EH.On secretion by the isolated kidney. J Physiol. 1922; 56:353–358
10. Eichholtz F.On some conditions affecting the perfusion of isolated mammalian organs. J Physiol. 1924; 59:340–344
11. Humphries AL Jr, Russell R, Gregory J, et al. Hypothermic perfusion of the canine kidney for 48 hours followed by reimplantation. Am Surg. 1964; 30:748–752
12. Belzer F, Ashby BS, Dunphy JE.24-hour and 72-hour preservation of canine kidneys. Lancet. 1967; 290:536–539
13. Atkins D, Eccles M, Flottorp S, et al. GRADE Working GroupSystems for grading the quality of evidence and the strength of recommendations I: critical appraisal of existing approaches The GRADE Working Group. BMC Health Serv Res. 2004; 4:38
14. Martins PN, Rizzari MD, Ghinolfi D, et al. Design, analysis, and pitfalls of clinical trials using ex situ liver machine perfusion: the International Liver Transplantation Society (ILTS) consensus guidelines I. Transplantation. 2021; 105:796–815