Removing Patients from the Liver Transplant Wait List: A Survey of US Liver Transplant Programs

Transcription

1 LIVER TRANSPLANTATION 14: , 2008 ORIGINAL ARTICLE Removing Patients from the Liver Transplant Wait List: A Survey of US Liver Transplant Programs Kevin P. Charpentier 1 and Arun Mavanur 2 1 Rhode Island Hospital, Department of Surgery, Division of Transplant Surgery, Providence, RI; and 2 Hartford Hospital, Department of Surgery, Division of General Surgery, Hartford, CT Guidelines are in place regarding who is a candidate for liver transplantation. Once a potential candidate is listed, there are no uniform guidelines indicating when he should be removed from the list because of a change in clinical status. A survey with 14 scenarios was sent to the medical and surgical directors of all liver transplant programs in the United States. In each scenario, clinical information was provided about a patient active on the transplant wait list. Data regarding a clinical change were provided, and responders were questioned whether they would remove the patient from the wait list. The scenarios were designed to address the issues of age, etiology of liver disease, renal dysfunction, respiratory failure, infection, failure to thrive, and social support. Two hundred four questionnaires were mailed with 47 responses (23%): 8 return to sender, 24 surgeons, and 15 hepatologists. All 11 United Network for Organ Sharing regions were represented. The responders were well distributed among university programs (n 28), private practice programs (n 10), and health maintenance organization programs (n 1). Nine responses were from small-volume programs ( 25 transplants), 12 were from medium-volume programs (26-50 transplants), and 18 were from large-volume programs ( 51 transplants). There was wide variability between responders regarding which patients should be removed from the transplant wait list. Patient age and etiology of liver disease led to the greatest discordance among responders. In conclusion, there is a lack of agreement and standardization among US liver transplant programs regarding who should be removed from the wait list for a change in clinical status. Liver Transpl 14: , AASLD. Received May 1, 2007; accepted August 20, Once activated on the liver transplant wait list, most patients are removed for 1 of 3 reasons: transplantation, death, or change in clinical status. Although transplantation and death are objective endpoints, change in clinical status is subjective, and its implications may vary between regions, centers, or even physicians within a center. Because of the progressive nature of many diseases serving as the indication for liver transplantation, mortality without transplantation is usually considered a forgone conclusion. Is anyone too sick to transplant? If so, who should proceed to transplantation and who should be removed from the liver transplant wait list either temporarily or permanently? To understand current practices for removing patients from the liver transplant wait list, we performed a survey of liver transplant programs in the United States. PATIENTS AND METHODS A questionnaire was sent to the medical and surgical directors of all liver transplant programs in the United States as listed in Clinical Transplants (Fig. 1). The questionnaire included 14 clinical scenarios. In Abbreviations: Cr, creatinine; CVVH, continuous venovenous hemofiltration; INR, international normalized ratio; MAP, mean arterial pressure; MELD, Model for End-Stage Liver Disease; PELD, pediatric end-stage liver disease; UNOS, United Network for Organ Sharing. Address reprint requests to Kevin P. Charpentier, M.D., Rhode Island Hospital, 593 Eddy Street, APC 921, Providence, RI Telephone: ; FAX: ; kcharpentier@lifespan.org DOI /lt Published online in Wiley InterScience ( American Association for the Study of Liver Diseases.

2 304 CHARPENTIER AND MAVANUR Figure 1. Questionnaire sent to the medical and surgical directors of all liver transplant programs in the United States describing a patient active on the liver transplant waiting list who experiences a change in clinical status. Abbreviations: Cr, creatinine; CVVH, continuous venovenous hemofiltration; INR, international normalized ratio; MAP, mean arterial pressure; MELD, Model for End-Stage Liver Disease. each scenario, a patient active on the liver transplant wait list is described. A change in clinical status is then described, and responders are asked if they would proceed with transplantation or remove the patient from the liver transplant wait list, either permanently or temporarily. For the purpose of this study, it was assumed that all relevant clinical information was provided in the scenarios. Scenarios 1 and 11 are ideal candidates for liver transplantation in the Model for End-Stage Liver Disease (MELD) system and are designed to test the validity of the questionnaire. Scenarios 1-4 address the issue of recipient age. Scenarios 3, 4, 7, and 11 address the issue of worsening renal function. Scenario 5 addresses the issue of social support. Scenario 6 addresses the issue of general deconditioning. Scenarios 8 and 12 address the issue of hemodynamic instability. Scenarios 9 and 13 address the issue of worsening respiratory failure. Scenarios 10 and 14 address the issue of infection in the recipient. Cumulatively, scenarios 7-10 and are designed to address the combined issues of age and etiology of liver disease. A chi-square test was used to determine the statistical significance of response differences between surgeons and hepatologists. RESULTS Two hundred three questionnaires were mailed. We received 47 (23%) responses: 8 return to sender and 39 (19%) completed surveys. The 39 responders represented 35 transplant centers and all 11 United Network for Organ Sharing (UNOS) regions. Twenty-three surgeons, 15 hepatologists, and

3 REMOVING PATIENTS FROM THE LIVER WAIT LIST 305 Figure 2. Responses to proceed with transplantation or remove the patient from the liver transplant waiting list due to a change in clinical status as detailed in the clinical scenarios in Fig transplant coordinator responded. The coordinator responded to a survey mailed to a surgeon; therefore, that questionnaire was grouped together with those of the other surgeons for analysis. The responders were well distributed among university programs (n 28), private practice programs (n 10), and health maintenance organization programs (n 1). Nine responses were from small-volume programs ( 25 transplants in 2004), 12 were from medium-volume programs (26-50 transplants in 2004), and 18 were from large-volume programs ( 51 transplants in 2004). Only 6 of 37 responders reported having a protocol in place for how patients are removed from the liver transplant list once activated. Responders reported average MELD scores of (n 7), (n 26), and (n 5). Individuals polled were queried as to whether they would remove a patient from the liver transplant wait list on the basis of a change in clinical status that occurred after the time of listing. The responses are summarized in Fig. 2. The breakdown of responses by hepatologists and surgeons is summarized in Table 1. Only scenarios 1 and 11 had 100% agreement among responders to proceed with transplantation. In all other scenarios, there were varying degrees of discordance between the decision to transplant or remove from the list. Areas of greatest discordance included renal failure in an older patient (scenario 4), recipient deconditioning determined by inability to ambulate (scenario 6), and rising vasopressor requirements or progressive respiratory failure in a young female with autoimmune hepatitis (scenarios 12 and 13, respectively). Four transplant centers submitted more than 1 completed survey; 3 centers submitted 2 surveys, and 1 center submitted 3 surveys. Answers varied between responders from within the same institution with a range of 3/14 (21%) to 8/14 (57%). Nine of 11 UNOS regions had more than 1 completed survey. Data from each region were analyzed separately and compared to the national response. Several interesting trends were noted. Region 1 centers unanimously agreed to remove the patient in case 6 from the list when he became nonambulatory. Region 1 programs also exhibited a trend to remove patients from the wait list when they became dependent on Neosynephrine for blood pressure support (cases 8 and 12). Responders from regions 2 and 5 trended toward exhibiting less variation between responders (more interresponder agreement). Additionally, responders from regions 2 and 5 appeared less influenced by advancing recipient age and were more likely to proceed with transplantation despite variations in age (cases 1-4). Finally, responders from region 8 were more likely to remove patients from the wait list because of advancing age (cases 1-4 and 7-14). Centers performing more than 10 living donor liver transplants annually had 100% agreement not to proceed with transplantation in patients requiring Neosynephrine for blood pressure support (cases 8 and 12). Centers without a competing liver transplant center in their donor service area were more likely to remove patients from the wait list because of advancing age (cases 1-4). DISCUSSION Indications for listing for liver transplantation are generally well accepted. Once a patient is listed, however, no uniform guidelines exist to determine when he should be removed from the liver transplant wait list because of a change in clinical status. We performed a survey of liver transplant programs throughout the United States. Nineteen percent of the medical and/or surgical directors surveyed responded. The response is a representative sample, as all 11 UNOS regions were represented with an adequate mix of large-volume and small-volume programs, university and private practice programs, and surgeons and hepatologists. Scenarios 1 and 11 represented ideal candidates for liver transplantation in the MELD era. One hundred percent agreement to proceed with transplantation in these scenarios helps to validate our questionnaire. There was wide variability in the decision to proceed with transplantation or remove patients from the liver transplant wait list for all other clinical scenarios, as depicted in Fig. 2 and Table 1. These data show that there is not uniform agreement among physicians in US transplant centers regarding when a patient becomes too sick for liver transplantation. With many patients awaiting liver transplantation facing nearly 100% predicted mortality over the short term, the question of being too sick for transplantation becomes challenging. What is acceptable perioperative mortality for liver transplantation? What is acceptable long-term survival post transplantation? The issue of acceptable risk must be considered in the context of either maximal patient benefit or maximal benefit to society. A model favoring maximum patient benefit would likely view high-risk patients, MELD 40, as those patients with the most perceived benefit. In the most extreme example, a predicted survival of 10% with transplantation is superior to 100% mortality for the individual patient. Although patients

4 306 CHARPENTIER AND MAVANUR TABLE 1. A Comparison of Responses of Hepatologists and Surgeons Regarding the Decision To Proceed with Transplantation or Remove the Patient from the Liver Transplant Waiting List due to a Change in Clinical Status as Detailed in the Clinical Scenarios in Fig. 1 Hepatologist Surgeon Case Transplant (n) Remove from List (n) Transplant (n) Remove from List (n) P Value with the highest MELD scores derive the most predicted benefit from liver transplantation, they are at the highest risk for being removed from the wait list for worsening clinical status. 2 Serial MELD scores and MELD have been suggested as means of minimizing wait-list mortality and dropout. 3 Our decisions are necessarily clouded by the organ shortage. In a utopia in which we had an unlimited supply of liver grafts, the decisions regarding candidacy for transplantation would clearly be broadened; however, reality is such that the organ shortage remains a major problem and concern for both transplant professionals and potential recipients. Pretransplant factors affecting patient survival following liver transplantation have been previously described and include donor age, recipient age, donor sodium, recipient creatinine, need for dialysis pretransplant, recipient ventilator requirement pre-transplant, and retransplantation. 4,5 In 1999, Rosen et al. 6 and Markmann et al. 6 independently published reports describing models to predict survival following retransplantation. There has not been universal agreement regarding how to apply these criteria to eliminate or exclude patients from the liver transplant wait list on the basis of expected outcomes In 2004, Olthoff et al. 10 issued a summary report of a national conference on the evolving concepts in liver allocation in the MELD and pediatric end-stage liver disease (PELD) era. Although the group endorsed the principle of transplant survival benefit as a major criteria for liver allocation, they did not feel that predictors of posttransplant survival were adequately defined to be incorporated into the allocation scheme at the time. With respect to the issue of removal of patients from the liver transplant wait list, the group suggested that an acceptable posttransplant survival rate should be targeted between 40% and 60%. Many questions were raised, illustrating the complexity of trying to standardize the process of removal of patients from the liver transplant wait list. 10 Freeman et al. 12 reported a trend toward fewer waitlist removals for the indications of death or too sick to transplant after the first year of the implementation of the MELD/PELD allocation system. This trend reached statistical significance for Hispanic and Asian candidates. Desai et al. 13 analyzed registry data from UNOS and found that MELD was a poor predictor of posttransplant survival for the majority of patients awaiting liver transplantation. They identified 4 preoperative variables independently associated with posttransplant survival: recipient age, mechanical ventilation, dialysis, and retransplantation. They reported a 57% 1-year survival strike (87% overall population) when patients had 2 of the following 3 preoperative variables: dialysis, mechanical ventilation, and retransplantation. On the basis of their results, the authors question the appropriateness of liver transplantation in patients meeting these criteria. Although this report confirms that there is wide variability in how physicians and transplant centers decide to remove patients from the liver transplant wait list for the indication of too sick to transplant, we are unable to make specific recommendations from the data because of the relatively small sample size of responders. In order to draw more substantial conclusions about how decisions to remove patients from the liver transplant wait list impact recipient outcomes and liver graft utilization, a larger, prospective, multicenter study would be necessary. In conclusion, there is no consensus opinion among US transplant professionals regarding who should be removed from the liver transplant wait list because of deterioration in clinical status. The challenge of determining who is too sick for liver transplantation continues to plague transplant professionals and likely will

5 REMOVING PATIENTS FROM THE LIVER WAIT LIST 307 remain at the forefront of our field for some time. Selection of the sickest candidates for liver transplantation relies on the art of surgery equally as much as the science of surgery. REFERENCES 1. Cecka JM, Terasaki PI, eds. Clinical Transplants Los Angeles, CA: UCLA Immunogenetics Center, 2003: Merion RM. When is a patient too well and when is a patient too sick for a liver transplant. Liver Transpl 2004; 10:S69-S Merion R, Wolfe RA, Dykstra DM, Leichtman AB, Gillespie B, Held PJ. Longitudinal assessment of mortality risk among candidates for liver transplantation. Liver Transpl 2003;9: Markmann JF, Markmann JW, Markmann DA, Bacquerizo A, Singer J, Holt CD, et al. Preoperative factors associated with outcome and their impact on resource use in 1148 consecutive primary liver transplants. Transplantation 2001;72: Gayowski T, Marino IR, Singh N, Doyle H, Wagener M, Fung J, et al. Orthotopic liver transplantation in high-risk patients: risk factors associated with mortality and infectious morbidity. Transplantation 1998;65: Rosen HR, Madden JP, Martin P. A model to predict survival following liver retransplantation. Hepatology 1999; 29: Markmann JF, Gornbein J, Markowitz JS, Levy M, Klintmalm G, Yersiz H, et al. A simple model to estimate survival after retransplantation of the liver. Transplantation 1999;67: Delmonico FL, Jenkins RL, Freeman R, Vacanti J, Bradley J, Dienstag JL, et al. The high-risk liver allograft recipient: should allocation policy consider outcome? Arch Surg 1992;127: Muto P, Freeman RB, Haug CE, Lu A, Rohrer R. Transplantation 1993;57: Euckhoff DE, Pirsch JD, D Alessandro AM, Knechtle SJ, Young CJ, Geffner SR, et al. Pretransplant status and patient survival following liver transplantation. Transplantation 1995;60: Olthoff KM, Brown RS Jr, Delmonico FL, Freeman R, McDiarmid J, Merion RM, et al. Summary report of a national conference: evolving concepts in liver allocation in the MELD/PELD era. Liver Transpl 2004;10:A6- A Freeman RB, Wiesner RH, Harper A, Edwards EB, Merion RB, Wolfe R. Results of the first year of the new liver allocation plan. Liver Transpl 2004;10: Desai NM, Mange KC, Crawford MD, Abt PL, Frank AM, Markmann JW, et al. Predicting outcome after liver transplantation: utility of the model for end-stage liver disease and a newly derived discrimination function. Transplantation 2004;77: