Gastroenterology
Volume 135, Issue 5 , Pages 1452-1454, November 2008

Using Higher Risk Organs for Liver Transplantation: In Whom and at What Price?

  • Bilal Hameed
    • ,
  • John R. Lake

      Affiliations

    • Corresponding Author InformationAddress requests for reprints to John R. Lake, MD, Professor, University of Minnesota, Division of Gastroenterology & Hepatology, 420 Delaware Street SE MMC 36, Minneapolis, MN 55455. fax 612-625-5620

Division of Gastroenterology and Hepatology, University of Minnesota, Minneapolis, Minnesota

published online 13 October 2008.

Article Outline

 

See “The impact of MELD allocation policy on utilization of high risk organs for liver transplantation,” by Volk ML, Lok AS, Pelltier SJ, et al, on page 1568.

An ongoing challenge in liver transplantation is the shortage of donor organs.1 To address the imbalance between donor organ availability and the number of potential recipients, new approaches to expand the donor pool have included living donor liver transplantation, split or partial liver transplantation, donation after cardiac death (DCD), and utilization of extended donor criteria (ECD) organs.

Allocation of livers using the Model for End-Stage Liver Disease (MELD) score was introduced on February 27, 2002. This objective score,2 based on 3 laboratory parameters (total serum bilirubin, International Normalized Ratio, and serum creatinine), changed the priority criteria from waiting time to one based on disease severity. MELD predicts 3-month mortality accurately for patients on the a liver transplant waiting list and can be applied for allocation of donor livers.3 Patients having a MELD score <9 have a 1.9% 3-month mortality, whereas patients having a MELD score ≥40 have a mortality rate of 71.3%. In addition, MELD can be used to predict the mortality risk after liver transplantation.4

Organs are allocated to patients in descending order of MELD score within each specific donor service area (DSA). This prioritization is termed as “local” (within the DSA), “regional” (within a United Network for Organ Sharing [UNOS] region), and “national.” When an organ is available, it is first directed to centers within the area (local). Allocating organs to regional patients with MELD ≥15, if no local patient have a MELD score ≥15 (the Share-15 rule), is an additional measure that attempts to direct livers to those most in need.5

Both donor and recipient risk factors influence liver transplantation outcomes. Feng et al6 used the Scientific Registry of Transplant Recipients (SRTR) to develop the concept of a Donor Risk Index (DRI).6 The DRI is a continuous measure that reflects the risk of graft failure (including death). It is composed of 8 simple donor parameters, including 3 donor demographic characteristics (age, race and height), 3 donor operative metrics (cold ischemia time, DCD, split liver/transplantation), and 2 other parameters (donor cause of death and distance between donor and recipient hospitals). The index ranges from a score of 0 to >2. Organs with a DRI of <1.0 have on average 3-year graft survival rates of 81% compared with only 60% for organs with a DRI of >2.0. DRI is not only useful in decision making about organ acceptance, but in the future may also be used in an allocation system that takes into account both donor and recipient variables.

In this issue of Gastroenterology, Volk et al7 sought to determine whether the quality of organs being transplanted have been affected by the MELD allocation policy. They also examined the types of patients receiving high-risk organs, and the implications of these findings on posttransplant survival. They showed that mean DRI had increased by 0.08 (which is equivalent to an 8% increase risk of graft failure) over the last 10 years. In the pre-MELD era, mean DRI increased at a rate of 0.006/year. In the post-MELD era, the DRI increased at a rate of 0.013/year. This additional increase in DRI since MELD implementation is equivalent to a 4% increase risk of graft failure (P < .001). Moreover, since the introduction of MELD allocation, more high DRI livers are being steered to patients with low MELD scores. In the past 10 years, there has been an increase in DRI of 0.14 in patients transplanted with MELD score <20. By contrast, the increase in the DRI of organs used to transplant patients with MELD >20 was only 0.03. Patients more likely to receive high DRI organs in the post-MELD era include those with (1) low MELD score, (2) less ascites, (3) older age, (4) no hepatitis C, and (5) no MELD exception or who were rejected for MELD exception. Patients with a MELD score <20 transplanted in the post-MELD era showed a decreased posttransplant survival rate (hazard ratio, 1.015 per year; P = .005). This change in survival can be explained by the increased use of high DRI organs.

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Why Is Donor Organ Quality Worsening? 

We suggest that it is probably unfair to entirely blame the change in MELD allocation for the increasing use of high DRI livers. In fact, several things have occurred since the institution of MELD allocation that we believe have made a greater contribution toward the increased use of high DRI livers and are independent of MELD allocation. First, the initiative by the Department of Health and Human Services, termed the Organ Donation Breakthrough Collaborative, has indeed succeeded to increase the number of deceased donor organs available for all types of organ transplantation. In fact, the results have really been quite dramatic.8 However, most of the additional organs available for transplant have come through the increased use of ECD. In fact, many of the factors that have been used to define ECD in kidney transplantation are included in the DRI calculation. Thus, we have observed a continuous increase in the age of deceased donors and perhaps most importantly, an increase in the number of organs from DCD, both of which lead to significant increases in the DRI. One of the major initiatives of the collaborative has been to increase the number of organs from DCD donors. Indeed, the number of livers from DCD donors has increased dramatically in the post MELD era.9

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Why Are High DRI Livers Being Used More Commonly for Low MELD Recipients? 

Schaubel et al10 first showed that median DRI tended to decrease as MELD score at transplant increased. The highest median DRI (1.50) was observed among patients transplanted while in the lowest MELD categories (6–8 and 9–11). Median DRI was 1.22 for patients transplanted with a MELD of 40.7 Similarly, using DRI of ≥1.7 as the definition of ECD, Maluf et al11 showed that between June 1, 2002 and June 30, 2005, recipients with MELD scores <15 received the highest percentage (33%) of ECD livers, whereas recipients in the highest MELD category (≥27) received the lowest percentage (18%). ECD livers were associated with a significant increase in the relative risk of graft failure within each MELD category. However, this effect held within each of the 3 MELD categories.

We believe the reasons for this are 2-fold. First, before the seminal paper by Merion et al,12 there certainly was the attitude that all wait-listed patients would obtain a survival benefit from liver transplantation. Indeed, if one examines the initial attempt at developing minimal listing criteria for liver transplantation,13 it is now clear that a significant percentage of patients who met minimal listing criteria would likely have had a MELD score of <14, and thus, would be unlikely to derive a survival benefit from liver transplantation. At the time these criteria were developed, there were not good metrics to determine the risk of wait list mortality such as we now have.

Second, the liver transplant community believed that more critically ill patients would have worse outcomes using high DRI livers. In this regard, the community was not wrong. Ioannou et al14 proposed a model of matching donors and recipients based on 4 donor variables (age, ischemia time, gender, and ethnicity) and 9 recipient variables (age, body mass index, MELD score, UNOS priority status, gender, ethnicity, diabetes mellitus, liver disease, and albumin level).14 The authors studied 5 possible matches: baseline donor–baseline recipient; best donor–best recipient; average donor–average recipient; average donor–high-risk recipient; and high-risk donor–high-risk recipient. In hepatitis C virus (HCV)–negative recipients, 5-year graft survivals ranged from 92%, in the best donor–best recipient match, to 28% in the high-risk donor–high-risk recipient match. Patients transplanted for HCV showed slightly worse survival, ranging from 84% to 29%.

However, we were wrong to direct the high DRI livers to the lower MELD recipients. Amin et al15 used a Markovian model with SRTR data to define the risk and benefit considerations for accepting or declining a liver offer according to the organ's potential for failure and the candidate's disease severity, as specified by MELD. They determined the 1-year survival was higher using an expanded criteria graft (ECD) versus waiting for the ideal graft in patients with MELD score of ≥20.15

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How Should We Go Forward With the Study Results? 

First, independent of the conclusions of the study, we need to learn how to better use high DRI livers. We also need to improve the outcomes using livers from DCD donors, and we need to determine how to better use high DRI livers in all patients. We are never going to be able to adequately serve our patients with advanced liver disease unless we are able to do so.

Second, we believe we need to develop a system of organ allocation that includes transplant benefit and does not simply prioritize patients based on critical illness alone. This indeed is part of the mandate of the Final Rule and is already a major component of the lung allocation system.

Liver transplant survival benefit varies across the range of MELD scores. To introduce the concept of transplant survival benefit, Merion et al12 compared recipient survival with that of comparable candidates remaining on the wait list. Only transplant recipients with a MELD score of ≥18, on average, derived a significant survival benefit with transplantation. By contrast, patients with low MELD scores had a lower mortality rate on the waiting list as compared with that with transplant and hence did not derive a survival benefit. The main limitations of this study were the mainly short follow-up of only 2 years and the fact that donor characteristics were not considered.

Recently, Schaubel et al10 estimated the survival benefit of liver transplantation by cross-classifications defined by MELD and DRI. In this study, the lowest MELD category recipients (MELD 6–8) who received high DRI organs experienced significantly higher mortality (hazard ratio, 3.70; P < .0005) as compared with remaining on the wait list. In fact, the use of high DRI livers in low MELD recipients substantially amplified the survival disadvantage of liver transplantation. By contrast, recipients with MELD ≥20, on average, had a significant survival benefit from transplantation, regardless of DRI. Indeed, even recipients with very high MELD scores (>35) still enjoyed a substantial transplant benefit. Transplantation of high DRI organs is effective for high but not low MELD candidates.

By using transplant benefit to allocate livers, we would avoid transplanting patients who are unlikely to benefit from transplantation using high DRI livers—an unwise transplant—and we would avoid transplanting the critically ill patient who has a high likelihood of dying after transplantation—the futile transplant.

Finally, in many parts of the country, the number of deceased donors is decreasing. In our local OPO in the upper Midwest, we have witnessed a nearly 30% decrease in the number of deceased donors. This is not a function of underutilization of deceased donors. Rather, it reflects a decrease in the number of potential deceased donors. This is an ominous trend for the future of solid organ transplantation in the United States; the reasons for this are not entirely clear at this point in time. However, this will further increase pressure to utilize all organs from potential deceased donors and likely will increase the pressure to increasingly use living donors as well.

The group from the University of Michigan is to be congratulated. They have led the way in helping us to determine how optimally to allocate livers to a critically ill group of patients. MELD has been a major advance in the equitable allocation of livers. It serves as the model for other organ groups that have examined allocation of their deceased donor organs. Although MELD has had some unintended consequences, such as a marked increase in the number of simultaneous liver–kidney transplants, we do not believe that it should be blamed for increasing the percentage of high DRI livers used for liver transplantation nor for using high DRI livers in relatively healthy recipients. In fact, it is only because MELD scoring has provided us with a better understanding of the severity of illness in our transplant recipients that we are even able to address these critical issues and hopefully further refine our liver allocation system to optimally serve our patients.

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References 

  1. Organ Procurement and Transplantation Network. Homepage on the Internet. http://www.optn.org
  2. Malinchoc M, Kamath PS, Gordon FD, et al. A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology. 2000;30:864
  3. Wiesner R, Edwards E, Freeman R, et al. United network for organ sharing liver disease severity score committee (Model for end-stage liver disease (MELD) and allocation of donor livers). Gastroenterology. 2003;124:91–96
  4. Saab S, Wang V, Ibrahim AB, et al. MELD score predicts 1-year patient survival post-orthotopic liver transplantation. Liver Transplantation. 2003;9:473–476
  5. 2006 Annual Report of the U.S. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients: Transplant Data 1994–2006. Rockville, MD: Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation; Richmond, VA: United Network for Organ Sharing; Ann Arbor, MI: University Renal Research and Education Association; 2006.
  6. 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;6:783–789
  7. Volk ML, Lok AS, Pelltier SJ, et al. Impact of the model for end-stage liver disease allocation policy on the use of high-risk organs for liver transplantation. Gastroenterology. 2008;135:1568–1574
  8. Shafer TJ, Wagner D, Chessare J, et al. US organ donation breakthrough collaborative increases organ donation. Crit Care Nurs Q. 2008;31:190–210
  9. Freeman RB, Steffick DE, Guidinger MK, et al. Liver and intestine transplantation in the United States, 1997-2006. Am J Transplant. 2008;8:958–976
  10. Schaubel DE, Sima CS, Goodrich NP, et al. The survival benefit of deceased donor liver transplantation as a function of candidate disease severity and donor quality. Am J Transplant. 2008;8:419–425
  11. Maluf DG, Edwards EB, Kauffman HM. Utilization of extended donor criteria liver allograft: is the elevated risk of failure independent of the model for end-stage liver disease score of the recipient?. Transplantation. 2006;82:1653–1657
  12. Merion RM, Schaubel DE, Dykstra DM, et al. The survival benefit of liver transplantation. Am J Transplant. 2005;5:307–313
  13. Lucey MR, Brown KA, Everson GT, et al. Minimal criteria for placement of adults on the liver transplant waiting list: a report of a national conference organized by the American Society of Transplant Physicians and the American Association for the Study of Liver Diseases. Liver Transplant Surg. 1997;3:628–637
  14. Ioannou GN. Development and validation of a model predicting graft survival after liver transplantation. Liver Transpl. 2006;12:1594–1606
  15. Amin MG, Wolf MP, TenBrook JA, et al. Expanded criteria donor grafts for deceased donor liver transplantation under the MELD system: a decision analysis. Liver Transpl. 2004;10:1468–1475

 The authors disclose no conflicts.

PII: S0016-5085(08)01766-6

doi:10.1053/j.gastro.2008.09.036

Refers to article:

  • Editorial Accompanies Article Impact of the Model for End-Stage Liver Disease Allocation Policy on the Use of High-Risk Organs for Liver Transplantation

    Michael L. Volk, Anna S.F. Lok, Shawn J. Pelletier, Peter A. Ubel, Rodney A. Hayward
    Gastroenterology November 2008 (Vol. 135, Issue 5, Pages 1568-1574)

Gastroenterology
Volume 135, Issue 5 , Pages 1452-1454, November 2008

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