Journal of Hepatology
Volume 51, Issue 4 , Pages 635-637, October 2009

Requiem for a champion? Living donor liver transplantation☆

  • Pierre-Alain Clavien

      Affiliations

    • Swiss HPB and Transplantation Centers, Department of Surgery, University Hospital of Zurich, Ramistrasse 100, 8091 Zurich, Switzerland
    • Corresponding Author InformationCorresponding author. Tel.: +41 1 2553300; fax: +41 1 2554449.
    • ,
  • Philipp Dutkowski

      Affiliations

    • Swiss HPB and Transplantation Centers, Department of Surgery, University Hospital of Zurich, Ramistrasse 100, 8091 Zurich, Switzerland
    • ,
  • James F. Trotter

      Affiliations

    • Baylor University Medical Center, 3500 Gaston Avenue, Dallas, TX 75246, USA

published online 05 August 2009.

Associate Editor: J.M. Llovet

Article Outline

Abbreviations: LDLT, living donor liver transplantation, MELD, model of end-stage liver disease

 

Since its widespread application in the late 90s, adult-to-adult LDLT has been the focus of many debates in Western countries. While the number of LDLT procedures peaked in 2001 in Europe and the USA, there has been, thereafter, a significant decrease of cases in the USA and no further increase in Europe (Fig. 1). For example, the number of patients undergoing LDLT dropped from 518 in 2001 to 318 in 2005 and to a projected figure of 168 in 2009, representing a 67% decrease, which currently represents only 3% of all adult liver transplantations performed in the USA.

The recent history of LDLT at the University of Pittsburgh has been the subject of considerable external scrutiny in the public press [1] and professional liver transplantation community. The manuscript by Marsh et al. [2] comprehensively describes the outcomes of right lobe LDLT donors and recipients at Pittsburgh since 2003, when the volumes of LDLT dramatically increased with the arrival of a new surgical team. While there are other single-center, retrospective studies from mature liver programs reporting complications, most of which were published 8–10 years ago, this manuscript is novel in at least three aspects compared to previous reports. First, it comes from Dr. Thomas E. Starzl, and every transplant physician would like to know his opinion on the procedure, because he has been uncharacteristically quiet with his written, public expression regarding LDLT during its expansive application in the past 20 years. Second, it is the most careful and timely analysis on this topic currently available and third it is a call for caution as complications may occur, even more frequently, after the learning curve is completed. Therefore, this publication from Pittsburgh, at this particular time, from this particular author with a strong statement about the safety and general application of LDLT is worthy of careful consideration.

The main message of this study is the high incidence of complications, particularly severe biliary complications, in recipients from LDLT, although one year patient/graft survival was, respectively, 91% and 84%. Those results for morbidity are somewhat alarming considering the elective nature of the procedure and the relatively low MELD scores (MELD<13 in most recipients) indicating a low risk of dying on the waiting list. Unexpectedly, the results even worsened during the last 2 years of the studied period, highlighting a potential risk for “relaxed vigilance once the procedure becomes routine”. While there was no donor death, a significant incidence of severe negative events was noted in the early postoperative period, mostly occurring in overweight living donors.

Acknowledging the unique relevance of this study, there are some criticisms, which must be discussed. The purpose of the study (as stated in the Introduction) is to clarify controversies surrounding LDLT simply by retrospectively reviewing 121 cases at their center over a 4-year period. Such a single-center study is not optimally configured to make this determination. Other series revealed a variety of results with usually lesser rates of postoperative negative events (Table 1). Noteworthy is the lower incidence of complications in the Asian series despite higher risk in recipients (MELD often>22). This better outcome is likely related to the use of thin donors and possibly better donor–recipient match. The results from a study recently published by the adult-to-adult living donor liver transplant study group (A2ALL) indicates a significant survival advantage from the selection of LDLT compared to remaining on the transplant list [3]. The A2ALL study is the largest analysis about recipient risk and benefit from the time of donor evaluation.

Table 1. Recipient outcome after right hemi-liver living donor liver transplantation.
AuthorPeriodnSurvivalMELDBiliary complicationsVascular complicationsNo serious complication
Marsh et al. [2]First half6095% (1y)1323 (38%)6 (10%)26 (43%)
Second half6187% (1y)1328 (46%)12 (20%)∗15 (25%)
Freise et al. [3]LDLT⩽20167#c1584 (50%)21 (13%)#c
LDLT>20217 77 (36%)∗15 (7%)
Chan et al. [6]Era Ia5086% (3y)29#c#c#c
Era II184 26
Shah et al. [7] 128#c1441 (32%)#c#c
Shah et al. [8] 15391% (1y)15#c#c#c
Hwang et al. [9] 215#c#c48 (21%)#c#c
Kokudo et al. [10] 11485% (3y)1731 (27%)8 (7%)#c
Icoz et al. [11] 5078% (1y)#c15 (30%)#c#c
Fan et al. [12] 100#c#c26 (26%)#c51 (51%)
Marcos et al. [13]Ab2080% (?)#c7 (35%)0#c
B2095% (?) 00
Testa et al. [14] 3080% (1y)#c8 (27%)#c#c

aLDLT between May 1996 and May 2006, Era I: first 50 cases, Era II: remaining 184 cases.

bA: LDLT between June and December 1998, B: LDLT between January and October 1999.

cNot reported.

∗p<0.05.

On the donor side, the statement in the Methods that there “are insurance-driven policies mandating prompt return of the donor to their primary care provider” is unusual in other areas in the US or elsewhere. Donors, can be, should be and, in fact, are seen or contacted at many centers for post-operative follow-up. We may suspect that in Pittsburgh the absence of such a protocol may likely lead to under-reporting of donor complications. Thus, the incidence of complications on the donor side might even be higher.

Despite those criticisms inherent in the study design, the conclusions drawn by the authors are critically important. For the first time, authors report an increasing incidence of complications in spite of increasing experience with better outcome (Table 1). This observation challenges the concept of the learning curve, as their incidence of complications increased with the number of cases performed, which is in contrast to every available report.

While this study does not offer the largest series of patients treated with this procedure, it is a most objective assessment of morbidity by the treatment based five-tier Clavien system [4], [5]. Logically, two questions arise consequently

•Are the results representative of the “real” world or are they more related to institutional problems of a single center?

•Is the data from other centers misleading because of less reported morbidity due to different and not comparable classification systems?

While many available studies provided a focus on donor morbidity, the data in terms of recipient outcome are mostly incomplete ([6], [7], [8], [9], [10], [11], [12], [13], [14], Table 1). Rarely standardized grading systems are applied and only limited series report on complication development over time. In addition, most single centers have yielded a lower incidence of biliary and vascular complications than reported here despite the use of higher MELD recipients. From that point of view, the answer to the above-mentioned questions will be decisive and will have a key impact on further policies to offer LDLT. The authors of this study provide new, objective and timely information which will be useful to better discuss LDLT. Of importance, they do not condemn right hemi-liver living donor liver transplantation, but make a call for appropriate monitoring of outcome, and a need for improvement to enable this approach to remain a viable option in some patients with cancer or end-stage liver diseases. The fact that complications increased over time within the same surgical team may serve as an alarming signal for all programs and help to ensure more accurate and continuous assessment of morbidity. Because the conclusions are those of the single most important liver transplant physician in the world, whose name is synonymous with the procedure, all LDLT physicians would be well-served by carefully reading the finale (the last four paragraphs) of this work as they continue their work in this important and ever-evolving field.

Back to Article Outline

References 

  1. Carreyrou J. Doing a volume business in liver transplants. Wall Street Journal; November 21, 2008.
  2. Marsh JW, Gray E, Ness R, Starzl TE. Complications of right lobe living donor liver transplantation. J Hepatol. 2009;51:715–724
  3. Freise CE, Gillespie BW, Koffron AJ, Lok ASF, Pruett TL, Emond JC, et al. Recipient morbidity after living and deceased donor liver transplantation: findings from the A2ALL retrospective cohort study. Am J Transplant. 2008;8:2569–2579
  4. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–213
  5. Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250:187–196
  6. Chan SC, Fan ST, Lo CM, Liu CL, Wei WI, Chik BHY, et al. A decade of right liver adult to adult living donor liver transplantation. Ann Surg. 2008;248:411–419
  7. Shah SA, Grant DR, McGilvray ID, Greig PD, Selzner M, Lilly LB, et al. Biliary strictures in 130 consecutive right lobe living donor liver transplant recipients: results of a western center. Am J Transplant. 2007;7:161–167
  8. Shah SA, Levy GA, Greig PD, Smith R, McGilvray ID, Lilly LB, et al. Reduced mortality with right lobe living donor compared to deceased donor liver transplantation when analyzed from the time of listing. Am J Transplant. 2007;7:998–1002
  9. Hwang S, Lee SG, Sung KB, Park KM, Kim KH, Ahn CS, et al. Long term incidence, risk factors, and management of biliary complications after adult living donor liver transplantation. Liver Transplant. 2006;12:831–838
  10. Kokudo N, Sugawara Y, Imamura H, Sano K, Makuuchi M. Tailoring the type of donor hepatectomy for adult living donor liver transplantation. Am J Transplant. 2005;5:1694–1703
  11. Icoz G, Kilic M, Zeytunlu M, Celebi A, Ersoz G, Killi R, et al. Biliary reconstructions and complications encountered in 50 consecutive right lobe living donor liver transplantations. Liver Transplant. 2003;9:575–580
  12. Fan ST, Lo CM, Liu CL, Yong BH, Wong J. Determinants of hospital mortality of adult recipients of right lobe live donor liver transplantation. Ann Surg. 2003;238:864–870
  13. Marcos A, Ham JM, Fisher RA, Olzinski AT, Posner MP. Single center analysis of the first 40 adult to adult living donor liver transplants using the right lobe. Liver Transplant. 2000;6:296–301
  14. Testa G, Malago M, Valentin-Gamazo C, Lindell G, Broelsch CE. Biliary anastomoses in living related liver transplantation using the right liver lobe: techniques and complications. Liver Transplant. 2000;6:710–714

☆ The authors declare that they do not have anything to disclose regarding funding from industries or conflict of interest with respect to this manuscript.

PII: S0168-8278(09)00521-2

doi:10.1016/j.jhep.2009.07.014

Refers to article:

  • Complications of right lobe living donor liver transplantation , 27 May 2009

    James W. Marsh, Edward Gray, Roberta Ness, Thomas E. Starzl
    Journal of Hepatology October 2009 (Vol. 51, Issue 4, Pages 715-724)

Journal of Hepatology
Volume 51, Issue 4 , Pages 635-637, October 2009

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