Three way liver exchange in Pakistan, reported in JAMA Surgery by Salman, Arsalan, and Dar, in collaboration with economist Alex Chan

 Here's an exciting account, just published in JAMA Surgery, of a three way liver exchange in Pakistan, achieved in part by collaboration with economist and market designer Alex Chan (who is on the job market this year).

Launching Liver Exchange and the First 3-Way Liver Paired Donation by Saad Salman, MD, MPH1; Muhammad Arsalan, MBBS2; Faisal Saud Dar, MBBS2, JAMA Surg. Published online December 7, 2022. doi:10.1001/jamasurg.2022.5440 (pdf)

Here are the first paragraphs:

"There is a shortage of transplantable organs almost everywhere in the world. In the US, about 6000 transplant candidates die waiting each year.1 In Pakistan, 30% to 50% of patients who needed a liver transplant are unable to secure a compatible donor, and about 10 000 people die each year waiting for a liver.2 Kidney paired donations, supported by Nobel Prize–winning kidney exchange (KE) algorithms,3 have enabled living donor kidneys to become an important source of kidneys. Exchanges supported by algorithms that systematically identify the optimal set of paired donations has yet to take hold for liver transplant.

"The innovation reported here is the successful implementation of a liver exchange mechanism4 that also led to 3 liver allotransplants and 3 hepatectomies between 3 incompatible patient-donor pairs with living donor–patient ABO/size incompatibilities. These were facilitated by one of the world’s first documented 3-way liver paired donations (LPD) between patient-donor pairs.

"Since 2018 and 2019, we have explored LPD as a strategy to overcome barriers for liver failure patients in Pakistan in collaboration with economist Alex Chan, MPH.2 With LPD, the incompatibility issues with relative donors can be solved by exchanging donors. The Pakistan Kidney and Liver Institute (PKLI) adopted a liver exchange algorithm developed by Chan4 to evaluate LPD opportunities that prioritizes clinical urgency (Model for End-stage Liver Disease [MELD] scores) while maximizing transplant-enabling 2-way or 3-way swaps that ensures that hepatectomies for every donor within each swap has comparable ex ante risk (to ensure fairness). As of March 2022, 20 PKLI liver transplant candidates had actively coregistered living and related but incompatible liver donors. Evaluating these 20 incompatible patient-donor pairs with the algorithm,4 we found 7 potential transplants by two 2-way swaps and the 3-way swap reported. In contrast to ad hoc manual identification of organ exchange opportunities, the hallmark of a scalable organ exchange program is the regular deployment of algorithms to systematically identify possible exchanges. Regular deployment of LPD algorithms is novel.

"A total of 6 procedures took place on March 17, 2022. Patient 1, a 57-year-old man, received a right liver lobe from donor 2, a 28-year-old coregistered donor of patient 2 (56-year-old man), who in turn received a right liver lobe from donor 3, a 35-year-old woman who was a coregistered donor of patient 3. Patient 3, a 46-year-old man, received a right liver lobe from donor 1, a 22-year-old woman who was a coregistered donor of patient 1, completing the cycle (Figure). Five PKLI consultant surgeons and 7 senior registrars led the hepatectomies and liver allotransplants; 6 operating rooms were used simultaneously. One month postsurgery, all patients and donors are robust with no graft rejection. All the donors are doing well in the follow-up visits and have shown no psychological issues."

Here's a sentence in the acknowledgements:

"We thank Alex Chan, MPH (Stanford University, Palo Alto, California), whose initiative and expertise in economics were the key driving forces for launching liver exchange."

*********

NB: this is a "Surgical Innovation" article, for which the journal requires that there be no more than three authors.

And here are the references cited:

1.

Chan  A, Roth  AE. Regulation of organ transplantation and procurement: a market design lab experiment. Accessed April 28, 2022. https://www.alexchan.net/_files/ugd/a47645_99b1d4843f2f42beb95b94e43547083b.pdf

2.

Salman  S, Gurev  S, Arsalan  M, Dar  F, Chan  A. Liver exchange: a pathway to increase access to transplantation. Accessed April 1, 2022. http://www.hhpronline.org/articles/2021/1/14/liver-exchange-a-pathway-to-increase-access-to-transplantation

3.

Henderson  D. On marriage, kidneys and the Economics Nobel. Wall Street Journal. October 15, 2012. Accessed March 5, 2022. https://www.wsj.com/articles/SB10000872396390443675404578058773182478536

4.

Chan  A. Optimal liver exchange with equipoise. Accessed April 23, 2022. https://www.alexchan.net/_files/ugd/a47645_36e252f4df0c4707b6431b0559b03143.pdf

5.

Hwang  S, Lee  SG, Moon  DB,  et al.  Exchange living donor liver transplantation to overcome ABO incompatibility in adult patients.   Liver Transpl. 2010;16(4):482-490. doi:10.1002/lt.22017PubMedGoogle ScholarCrossref

6.

Patel  MS, Mohamed  Z, Ghanekar  A,  et al.  Living donor liver paired exchange: a North American first.   Am J Transplant. 2021;21(1):400-404. doi:10.1111/ajt.16137PubMedGoogle ScholarCrossref

7.

Braun  HJ, Torres  AM, Louie  F,  et al.  Expanding living donor liver transplantation: report of first US living donor liver transplant chain.   Am J Transplant. 2021;21(4):1633-1636. doi:10.1111/ajt.16396

 ********

Here's a Stanford story on this collaboration:

Stanford student devises liver exchange, easing shortage of organs. A rare three-way exchange of liver transplants in Pakistan was made possible with a new algorithm developed by a Stanford Medicine student.  by Nina Bai

"The liver exchange idea actually came out of a term paper in a first-year market design class at Stanford," Chan said.

"As he learned more about liver transplants, Chan realized there were important biological and ethical differences from kidney transplants. 

...

"Instead of just finding compatible swaps, we want to find swaps that prioitize the most urgent patients first in order to prevent the most deaths," Chan said.

*******

Here are some contemporaneous stories from March in the newspaper Dawn (now that the JAMA embargo on the story is lifted):

Liver transplants at PKLI under 'swap' plan - Newspaper - Dawn

Mar 18, 2022 — A highly-trained team of the surgeons headed by PKLI Dean Prof Faisal Dar had performed liver transplants at the institute and other members ...

• First swap liver transplant surgeries at PKLI today - Dawn

  
  

  Mar 17, 2022 — An official told Dawn on Wednesday the treating doctors had recommended liver transplant of all the three patients due to their end-stage ...

Liver exchange--a review by Agrawal, Gupta and Saigal

 

 Here's a review of liver exchange in the transplant literature, with some comparisons to kidney exchange.

Paired exchange Living donor Liver Transplantation: Indications, stumbling blocks, and future considerations by Dhiraj Agrawal, Subhash Gupta,  and Sanjiv Saigal, Journal of Hepatology, In Press,  Pre-proof https://doi.org/10.1016/j.jhep.2022.10.019 

Abstract: "The last decade has seen Liver Paired exchange (LPE) as an increasingly used modality across the transplant community by which pairs of incompatible living Liver donors and their intended recipients swap Livers resulting in compatible transplants. The feasibility and benefit of LPE in providing excellent recipient outcomes and robust donor safety have been proven in uncomplicated swaps. Began initially as single-centre two-way or three-way exchanges, LPE has tremendous potential to grow into more complicated chains over days and over multiple centres. Also, LPE is associated with unique technical, logistical, ethical and legislative challenges. This review discusses the indications, potential types of LPE, unique solutions to stumbling blocks in performing LPE, and future considerations on how LPE can expand the living donor liver pool and the armamentarium of living donor liver transplantation (LDLT)".

"The published literature on LPE has nine reports (5 original articles and 4 case reports), including 74 LPEs from Asia and North America.1), 2), 3), 4), 5), 6), 7), 8), 9) LPE constitutes approximately 1.2 to 8.3 % of the total LDLTs performed at the individual centre1), 2), 3), 4), signifying a substantial potential of this form of LDLT to mitigate the liver allograft shortage."

...

1. D. Agrawal, S. Saigal, S.S. Jadaun, S.A. Singh, S. Agrawal, S. Gupta

Paired Exchange Living Donor Liver Transplantation: A Nine-year Experience From North India

Transplantation (2022 Jun 30), 10.1097/TP.0000000000004210

Epub ahead of print. PMID: 35777310

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2)

S. Hwang, S.G. Lee, D.B. Moon, G.W. Song, C.S. Ahn, K.H. Kim, et al.

Exchange living donor liver transplantation to overcome ABO incompatibility in adult patients

Liver Transpl, 16 (4) (2010 Apr), pp. 482-490, 10.1002/lt.22017

PMID: 20222052

 View PDF

View Record in ScopusGoogle Scholar

3)

D.H. Jung, S. Hwang, C.S. Ahn, K.H. Kim, D.B. Moon, S.G. Lee, et al.

Section 16. Update on experience in paired-exchange donors in living donor liver transplantation for adult patients at ASAN Medical Center

Transplantation, 97 (Suppl 8) (2014 Apr 27), pp. S66-S69, 10.1097/01.tp.0000446280.81922.bb

PMID: 24849838

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V. Gunabushanam, S. Ganesh, K. Soltys, G. Mazariegos, A. Ganoza, M. Molinari, et al.

Increasing Living Donor Liver Transplantation Using Liver Paired Exchange

J Am Coll Surg, 234 (2) (2022 Feb 1), pp. 115-120, 10.1097/XCS.0000000000000036

PMID: 35213430

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5)

A. Kaplan, R. Rosenblatt, W. Jackson, B. Samstein, R.S. Brown Jr.

Practices and Perceptions of Living Donor Liver Transplantation, Non-directed Donation, and Liver Paired Exchange: A National Survey

Liver Transpl, 28 (5) (2022 May), pp. 774-781, 10.1002/lt.26384

Epub 2021 Dec 26. PMID: 34862704; PMCID: PMC9018478

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6)

H.J. Braun, A.M. Torres, F. Louie, S.D. Weinberg, S.M. Kang, N.L. Ascher, et al.

Expanding living donor liver transplantation: Report of first US living donor liver transplant chain

Am J Transplant, 21 (4) (2021 Apr), pp. 1633-1636, 10.1111/ajt.16396

Epub 2020 Dec 8. PMID: 33171017; PMCID: PMC8016700

 View PDF

This article is free to access.

View Record in ScopusGoogle Scholar

7)

M.S. Patel, Z. Mohamed, A. Ghanekar, G. Sapisochin, I. McGilvray, N. Selzner, et al.

Living donor liver paired exchange: A North American first

Am J Transplant, 21 (1) (2021 Jan), pp. 400-404, 10.1111/ajt.16137

Epub 2020 Jul 10. PMID: 32524750

 View PDF

This article is free to access.

View Record in ScopusGoogle Scholar

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S.C. Chan, C.M. Lo, B.H. Yong, W.J. Tsui, K.K. Ng, S.T. Fan

Paired donor interchange to avoid ABO-incompatible living donor liver transplantation

Liver Transpl, 16 (4) (2010 Apr), pp. 478-481, 10.1002/lt.21970

PMID: 20373459

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S.C. Chan, Chok KSh, W.W. Sharr, A.C. Chan, S.H. Tsang, W.C. Dai, et al.

Samaritan donor interchange in living donor liver transplantation

Hepatobiliary Pancreat Dis Int, 13 (1) (2014 Feb), pp. 105-109, 10.1016/s1499-3872(14)60016-3

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Kidney exchange collaboration between Stanford and APKD

 I recently had occasion to review the long collaboration between my Stanford colleagues and Mike Rees and the Alliance for Paired Kidney Donation. It turns out that, together with other coauthors, Mike and his APKD colleagues have written well over a dozen papers with me and my colleagues at Stanford.  (My own collaboration with Mike and APKD goes back to when Itai Ashlagi and I were still in Boston, where my earliest papers on kidney exchange were with  Tayfun Sönmez and Utku Ünver, and with Frank Delmonico and his colleagues at the New England Program for Kidney Exchange.)

Here's the list I came up with, probably not exhaustive:

Mike Rees/APKD collaborations with Stanford scholars (Ashlagi, Melcher, Roth, Somaini)

 1. Rees, Michael A., Jonathan E. Kopke, Ronald P. Pelletier, Dorry L. Segev, Matthew E. Rutter, Alfredo J. Fabrega, Jeffrey Rogers, Oleh G. Pankewycz, Janet Hiller, Alvin E. Roth, Tuomas Sandholm, Utku Ünver, and Robert A. Montgomery, “A Non-Simultaneous Extended Altruistic Donor Chain,” New England Journal of Medicine, 360;11, March 12, 2009, 1096-1101. https://www.nejm.org/doi/full/10.1056/NEJMoa0803645

2.     Ashlagi, Itai, Duncan S. Gilchrist, Alvin E. Roth, and Michael A. Rees, “Nonsimultaneous Chains and Dominos in Kidney Paired Donation – Revisited,” American Journal of Transplantation, 11, 5, May 2011, 984-994 http://www.stanford.edu/~alroth/papers/Nonsimultaneous%20Chains%20AJT%202011.pdf

3.     Ashlagi, Itai, Duncan S. Gilchrist, Alvin E. Roth, and Michael A. Rees, “NEAD Chains in Transplantation,” American Journal of Transplantation, December 2011; 11: 2780–2781. http://web.stanford.edu/~iashlagi/papers/NeadChains2.pdf

4.     Wallis, C. Bradley, Kannan P. Samy, Alvin E. Roth, and Michael A. Rees, “Kidney Paired Donation,” Nephrology Dialysis Transplantation, July 2011, 26 (7): 2091-2099 (published online March 31, 2011; doi: 10.1093/ndt/gfr155, https://academic.oup.com/ndt/article/26/7/2091/1896342/Kidney-paired-donation

5.     Rees, Michael A.,  Mark A. Schnitzler, Edward Zavala, James A. Cutler,  Alvin E. Roth, F. Dennis Irwin, Stephen W. Crawford,and Alan B.  Leichtman, “Call to Develop a Standard Acquisition Charge Model for Kidney Paired Donation,” American Journal of Transplantation, 2012, 12, 6 (June), 1392-1397. (published online 9 April 2012 http://onlinelibrary.wiley.com/doi/10.1111/j.1600-6143.2012.04034.x/abstract )

6.     Anderson, Ross, Itai Ashlagi, David Gamarnik, Michael Rees, Alvin E. Roth, Tayfun Sönmez and M. Utku Ünver, " Kidney Exchange and the Alliance for Paired Donation: Operations Research Changes the Way Kidneys are Transplanted," Edelman Award Competition, Interfaces, 2015, 45(1), pp. 26–42. http://pubsonline.informs.org/doi/pdf/10.1287/inte.2014.0766

7.     Fumo, D.E., V. Kapoor, L.J. Reece, S.M. Stepkowski,J.E. Kopke, S.E. Rees, C. Smith, A.E. Roth, A.B. Leichtman, M.A. Rees, “Improving matching strategies in kidney paired donation: the 7-year evolution of a web based virtual matching system,” American Journal of Transplantation, October 2015, 15(10), 2646-2654 http://onlinelibrary.wiley.com/enhanced/doi/10.1111/ajt.13337/ (designated one of 10 “best of AJT 2015”)

8.     Melcher, Marc L., John P. Roberts, Alan B. Leichtman, Alvin E. Roth, and Michael A. Rees, “Utilization of Deceased Donor Kidneys to Initiate Living Donor Chains,” American Journal of Transplantation, 16, 5, May 2016, 1367–1370. http://onlinelibrary.wiley.com/doi/10.1111/ajt.13740/full

9.     Michael A. Rees, Ty B. Dunn, Christian S. Kuhr, Christopher L. Marsh, Jeffrey Rogers, Susan E. Rees, Alejandra Cicero, Laurie J. Reece, Alvin E. Roth, Obi Ekwenna, David E. Fumo, Kimberly D. Krawiec, Jonathan E. Kopke, Samay Jain, Miguel Tan and Siegfredo R. Paloyo, “Kidney Exchange to Overcome Financial Barriers to Kidney Transplantation,” American Journal of Transplantation, 17, 3, March 2017, 782–790. http://onlinelibrary.wiley.com/doi/10.1111/ajt.14106/full  

a.     M. A. Rees, S. R. Paloyo, A. E. Roth, K. D. Krawiec, O. Ekwenna, C. L. Marsh, A. J. Wenig, T. B. Dunn, “Global Kidney Exchange: Financially Incompatible Pairs Are Not Transplantable Compatible Pairs,” American Journal of Transplantation, 17, 10, October 2017, 2743–2744. http://onlinelibrary.wiley.com/doi/10.1111/ajt.14451/full

b.     A. E. Roth, K. D. Krawiec, S. Paloyo, O. Ekwenna, C. L. Marsh, A. J. Wenig, T. B. Dunn, and M. A. Rees, “People should not be banned from transplantation only because of their country of origin,” American Journal of Transplantation, 17, 10, October 2017, 2747-2748. http://onlinelibrary.wiley.com/doi/10.1111/ajt.14485/full

c.      Ignazio R. Marino, Alvin E. Roth, Michael A. Rees; Cataldo Doria, “Open dialogue between professionals with different opinions builds the best policy, American Journal of Transplantation, 17, 10, October 2017, 2749. http://onlinelibrary.wiley.com/doi/10.1111/ajt.14484/full

10.  Danielle Bozek, Ty B. Dunn, Christian S. Kuhr, Christopher L. Marsh, Jeffrey Rogers, Susan E. Rees, Laura Basagoitia, Robert J. Brunner, Alvin E. Roth, Obi Ekwenna, David E. Fumo, Kimberly D. Krawiec, Jonathan E. Kopke, Puneet Sindhwani, Jorge Ortiz, Miguel Tan, and Siegfredo R. Paloyo, Michael A. Rees, “The Complete Chain of the First Global Kidney Exchange Transplant and 3-yr Follow-up,” European Urology Focus, 4, 2, March 2018, 190-197. https://www.sciencedirect.com/science/article/pii/S2405456918301871

11.  Itai Ashlagi, Adam Bingaman, Maximilien Burq, Vahideh Manshadi, David Gamarnik, Cathi Murphey, Alvin E. Roth,  Marc L. Melcher, Michael A. Rees, ”The effect of match-run frequencies on the number of transplants and waiting times in kidney exchange,” American Journal of Transplantation, 18, 5, May 2018,  1177-1186, https://onlinelibrary.wiley.com/doi/full/10.1111/ajt.14566

12.   Stepkowski, S. M., Mierzejewska, B., Fumo, D., Bekbolsynov, D., Khuder, S., Baum, C. E., Brunner, R. J., Kopke, J. E., Rees, S. E., Smith, C. E., Ashlagi, I., Roth, A. E., Rees, M. A., “The 6-year clinical outcomes for patients registered in a multiregional United States Kidney Paired Donation program- a retrospective study,” Transplant international 32: 839-853. 2019. https://onlinelibrary.wiley.com/doi/10.1111/tri.13423

13.   Roth, Alvin E., Ignazio R. Marino, Obi Ekwenna, Ty B. Dunn, Siegfredo R. Paloyo, Miguel Tan, Ricardo Correa-Rotter, Christian S. Kuhr, Christopher L. Marsh, Jorge Ortiz, Giuliano Testa, Puneet Sindhwani, Dorry L. Segev, Jeffrey Rogers, Jeffrey D. Punch, Rachel C. Forbes, Michael A. Zimmerman, Matthew J. Ellis, Aparna Rege, Laura Basagoitia, Kimberly D. Krawiec, and Michael A. Rees, “Global Kidney Exchange Should Expand Wisely, Transplant International, September 2020, 33, 9,  985-988. https://onlinelibrary.wiley.com/doi/full/10.1111/tri.13656

14.  Vivek B. Kute, Himanshu V. Patel, Pranjal R. Modi, Sayyad J. Rizvi, Pankaj R. Shah, Divyesh P Engineer, Subho Banerjee, Hari Shankar Meshram, Bina P. Butala, Manisha P. Modi, Shruti Gandhi, Ansy H. Patel, Vineet V. Mishra, Alvin E. Roth, Jonathan E. Kopke, Michael A. Rees, “Non-simultaneous kidney exchange cycles in resource-restricted countries without non-directed donation,” Transplant International,  Volume 34, Issue 4, April 2021,  669-680  https://doi.org/10.1111/tri.13833

15.   Afshin Nikzad, Mohammad Akbarpour, Michael A. Rees, and Alvin E. Roth “Global Kidney Chains,” Proceedings of the National Academy of Sciences, September 7, 2021 118 (36) e2106652118; https://doi.org/10.1073/pnas.2106652118 .

16.    Alvin E. Roth, Ignazio R. Marino, Kimberly D. Krawiec, and Michael A. Rees, “Criminal, Legal, and Ethical Kidney Donation and Transplantation: A Conceptual Framework to Enable Innovation,” Transplant International  (2022), 35: doi: 10.3389/ti.2022.10551, https://www.frontierspartnerships.org/articles/10.3389/ti.2022.10551/full

17.   Ignazio R. Marino, Alvin E. Roth, and Michael A. Rees, “Living Kidney Donor Transplantation and Global Kidney Exchange,” Experimental and Clinical Transplantation (2022), Suppl. 4, 5-9. http://www.ectrx.org/class/pdfPreview.php?year=2022&volume=20&issue=8&supplement=4&spage_number=5&makale_no=0

18.  Agarwal, Nikhil, Itai Ashlagi, Michael A. Rees, Paulo Somaini, and Daniel Waldinger. "Equilibrium allocations under alternative waitlist designs: Evidence from deceased donor kidneys." Econometrica 89, no. 1 (2021): 37-76.

And here’s a report of work in progress:

The First 52 Global Kidney Exchange Transplants: overcoming multiple barriers to transplantation by MA Rees, AE Roth , IR Marino, K Krawiec, A Agnihotri, S Rees, K Sweeney, S Paloyo, T Dunn, M Zimmerman, J Punch, R Sung, J Leventhal, A Alobaidli, F Aziz, E Mor, T Ashkenazi, I Ashlagi, M Ellis, A Rege, V Whittaker, R Forbes, C Marsh, C Kuhr, J Rogers, M Tan, L Basagoitia, R Correa-Rotter, S Anwar, F Citterio, J Romagnoli, and O Ekwenna.  Transplantation: September 2022 - Volume 106 - Issue 9S - p S469 doi: 10.1097/01.tp.0000887972.53388.77  https://journals.lww.com/transplantjournal/Fulltext/2022/09001/423_9__The_First_52_Global_Kidney_Exchange.697.aspx