Live Donor Liver Transplantation: Is It Better Than Waiting?

Abstract

See “Improvement in survival associated with adult-to-adult living donor liver transplantation” by Berg CL, Gillespie BW, Merion RM, et al, on page 1806.Liver transplantation is a well accepted therapy for patients with liver failure. In 2006, 6650 liver transplants were performed in the United States.1The Organ Procurement and Transplantation Network, 2003. Available at: www.optn.org/latestData/rptData.asp. Accessed October 13, 2007.Google Scholar Tragically, many more patients are in need, with >17,000 patients currently on the waiting list. Indeed, the field is a victim of its own success. As success rates have improved and awareness has increased, it is rare that patients with acute or chronic liver failure are not discussed with the local transplant center. Unfortunately, some patients die before a transplant can be performed.The risk of death on the wait list has not been ignored. In an attempt to allocate donor organs to the sickest patients first, the Organ and Procurement Transplantation Network changed its allocation system for livers from one based on a combination of the Child–Turcotte–Pugh score and time on the waiting list to the current Model for End-Stage Liver Disease (MELD). MELD is the complex mathematical formula used to establish the likelihood of 3-month mortality using easily obtainable values for total bilirubin, serum creatinine, and International Normalized Ratio.2Malinchoc M. Kamath P.S. Gordon F.D. et al.A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts.Hepatology. 2000; 31: 864-871Crossref PubMed Scopus (2068) Google ScholarThe use of donor organs previously thought unfit for transplantation has increased the number of liver transplants. For example, hepatitis C-positive donors, hepatitis B core antibody–positive donors, and older donors have been used successfully in selected recipients. The approach to a liver transplant has evolved from the goal of transplanting the first patient on the wait list, to transplanting the right organ into the right recipient. But the evolution of matching donors and recipients above and beyond blood type and body size has not eliminated death on the waiting list, as the availability of deceased organ donors continues to lag behind the number of those waiting. Thus, the use of live organ donors has further expanded the donor pool.The use of an organ from a living donor has roots >50 years old. Doctor Joseph Murray performed a successful kidney transplant from 1 twin brother to another in 1954. In 2006, nearly 38% of all kidney transplants were from live donors.1The Organ Procurement and Transplantation Network, 2003. Available at: www.optn.org/latestData/rptData.asp. Accessed October 13, 2007.Google Scholar The use of live donors for liver transplants is a more recent, although less common, event. In 2006, 4.3% of liver transplants in this country were performed using a live donor.1The Organ Procurement and Transplantation Network, 2003. Available at: www.optn.org/latestData/rptData.asp. Accessed October 13, 2007.Google ScholarThree major questions regarding live donor liver transplantation (LDLT) must be the source of ongoing study (Table 1): (1) Will a recipient live after a live donor transplant? (2) Does living donor transplantation decrease the risk of death versus waiting for a deceased organ donor? (3) Can the procedure be performed to ensure the safety and well-being of the donor? Although each question is unique, these questions are nonetheless interrelated, particularly as a transplant recipient and a potential living donor consider the option of LDLT. For example, a potential recipient would likely not consider a LDLT if there were a significant risk to the life and health of the donor. Likewise, if the donor procedure was simple and safe, but posttransplant survival rates were significantly lower than those in deceased donor recipients, further discussion would be unnecessary.Table 1Key Issues for Live Donor Liver TransplantationRecipient survivalDecreased wait list mortalityDonor selectionDonor safetyDonor follow-up Open table in a new tab To answer questions regarding LDLT, the National Institutes of Health funded the Adult-to-Adult Living Donor Transplantation Retrospective Cohort Study (A2ALL) in 2002. Nine centers across the country were included with the primary objective of answering the question of survival benefit. In this issue of Gastroenterology, the A2ALL group presents data regarding the effect of living donor transplantation on wait list mortality.3Berg C.L. Gillespie B.W. Merion R.M. et al.Improvement in survival associated with adult-to-adult living donor liver transplantation.Gastroenterology. 2007; 133: 1806-1813Abstract Full Text Full Text PDF PubMed Scopus (152) Google Scholar The group studied 807 patients who presented with ≥1 potential living donor candidate. Patients with acute liver failure were not included in the study. The study followed those who ultimately received a LDLT and compared their survival with those who presented with a potential living donor candidate but did not receive a LDLT. Patients in the latter group subsequently received a deceased donor transplant, continued to wait for the appropriate deceased donor organ, or died on the waiting list.The study shows that those who received a LDLT had improved survival when compared with those presenting with a potential donor, but did not receive a LDLT. Survival rates in those receiving a LDLT were similar to those receiving a deceased donor transplant. Furthermore, early retransplants (<3 weeks after the initial transplant) were more common in the living donor recipients. Survival rates in the living donor recipients improved and early retransplants decreased when the transplant center volume exceeded 20 living donor transplants. Thus, center experience is a pivotal factor in survival after LDLT.Center experience may have had an effect on the volume of patients studied over time at the A2ALL centers. An increase in the percentage of patients studied was observed from 1998, the first year patients were enrolled, up to the implementation of MELD in 2002. After the implementation of MELD, the percentage of patients undergoing LDLT decreased from 35% to 19% of the total, and those presenting with a potential live donor, but not receiving a LDLT, decreased from 36% to 30%. One can only speculate about the reasons for this pattern. LDLT was a novel approach initially, and met with great enthusiasm; perhaps awareness led to more patients who presented with potential donors, more of whom were unacceptable. Perhaps this enthusiasm waned over time, particularly if donor complications occurred. The implementation of MELD led to allocation of deceased donor organs to sicker patients, possibly decreasing the need for LDLT. Finally, the effect of center experience cannot be discounted. Experience with technical issues and donor selection may have led to more stringent criteria for recipients and donors.One potential flaw in this study is selection bias. It should be borne in mind those patients investigated presented with ≥1 potential living donor. Many patients are never even considered as a living donor recipient for a variety of reasons. Prior operations with subsequent adhesions or anatomic variants that potentially increase the complexity of transplantation with a deceased donor, much less the added complexity of a live donor, can make LDLT untenable. Donor issues, such as underlying medical conditions, obesity with or without hepatic steatosis, and previous operations increase risk for both the donor and the recipient. Imagine the following scenario: a 60-year-old, 5’2” tall, 100-pound woman with primary biliary cirrhosis shows up with her “potential” donor, her 67-year-old, 5’3” tall, 220-pound, tobacco-dependent, diabetic sister with coronary artery disease. An appropriate live liver donor? No, but a “potential” donor, just the same. The point is that recipients and donors may be deemed inappropriate after a history and physical examination. The authors state this only accounted for 21% of those in the comparison group; however, this does raise the question of whether including these patients in the analysis is appropriate. Specifically, because the potential donor was unacceptable “at the door,” does this affect the comparison group by shifting patients who never really had a chance for LDLT into this group? Further interrogation of the comparison group reveals those receiving a LDLT had lower MELD scores, were significantly younger, had better occupational histories and functional status, and were more likely to be female. Although these issues may influence the analysis, perhaps the process of LDLT itself engenders selection bias. For example, only 10% of potential liver transplant recipients at these centers even had a potential liver donor. Previous studies have shown only 30% of donors are deemed acceptable,4Trotter J.F. Wachs M. Trouillot T. et al.Evaluation of 100 patients for living donor liver transplantation.Liver Transpl. 2000; 6: 290-295Crossref PubMed Scopus (110) Google Scholar although 48.2% received a LDLT in this study. With such a highly selected population, one would assume survival rates would be better than waiting for a deceased donor. Nevertheless, this study is the first to demonstrate data supporting such a conclusion.Unfortunately, LDLT accounts for only 3%–5% of all transplants. Does every organ help? Of course. However, more information is needed about the long-term outcomes of both recipients and donors before patients can accept this process as a safe and viable alternative to deceased donor transplantation. Although this study focused on the effect of LDLT on wait-list mortality, donor safety cannot be ignored. Such follow-up, ideally in the form of a national database, will likely require federal funding, owing to the enormity of the project. Many live donors move out of the area or refuse follow-up care owing to expense and the apparent lack of long-term complications. Only detailed follow-up and analysis, however, will answer the important questions regarding long-term complications.Data on donor safety are of paramount importance; however, many willing donors may not donate because of the financial disincentives associated with the procedure. Live liver donors frequently are away from work for 4–8 weeks. The Organ Donor Leave Act from 1999 guarantees pay for 30 days for federal employees after organ donation. Many states and corporations have similar programs. However, the potential salary loss surrounding donor surgery may not be the end of financial issues. After organ donation, many donors may become “uninsurable” owing to this new “preexisting” condition. As crucial as donor safety is, financial hardship interfering and even preventing live organ donation is absurd. Perhaps automatic eligibility for lifetime federal or state health care benefits, when needed, is required for these heroic efforts.The answers to these questions are not easy. This study shows, for the first time, that having a LDLT does lead to a survival advantage when compared with those with a potential living donor who do not have a LDLT. The transplant community, led by the A2ALL group, needs to continue to refine all aspects of LDLT, from donor and recipient selection to long-term follow-up, with the understanding that ongoing analysis is the only way important questions can be answered and those answers applied to the care of potential transplant recipients and live organ donors. See “Improvement in survival associated with adult-to-adult living donor liver transplantation” by Berg CL, Gillespie BW, Merion RM, et al, on page 1806. See “Improvement in survival associated with adult-to-adult living donor liver transplantation” by Berg CL, Gillespie BW, Merion RM, et al, on page 1806. See “Improvement in survival associated with adult-to-adult living donor liver transplantation” by Berg CL, Gillespie BW, Merion RM, et al, on page 1806. Liver transplantation is a well accepted therapy for patients with liver failure. In 2006, 6650 liver transplants were performed in the United States.1The Organ Procurement and Transplantation Network, 2003. Available at: www.optn.org/latestData/rptData.asp. Accessed October 13, 2007.Google Scholar Tragically, many more patients are in need, with >17,000 patients currently on the waiting list. Indeed, the field is a victim of its own success. As success rates have improved and awareness has increased, it is rare that patients with acute or chronic liver failure are not discussed with the local transplant center. Unfortunately, some patients die before a transplant can be performed. The risk of death on the wait list has not been ignored. In an attempt to allocate donor organs to the sickest patients first, the Organ and Procurement Transplantation Network changed its allocation system for livers from one based on a combination of the Child–Turcotte–Pugh score and time on the waiting list to the current Model for End-Stage Liver Disease (MELD). MELD is the complex mathematical formula used to establish the likelihood of 3-month mortality using easily obtainable values for total bilirubin, serum creatinine, and International Normalized Ratio.2Malinchoc M. Kamath P.S. Gordon F.D. et al.A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts.Hepatology. 2000; 31: 864-871Crossref PubMed Scopus (2068) Google Scholar The use of donor organs previously thought unfit for transplantation has increased the number of liver transplants. For example, hepatitis C-positive donors, hepatitis B core antibody–positive donors, and older donors have been used successfully in selected recipients. The approach to a liver transplant has evolved from the goal of transplanting the first patient on the wait list, to transplanting the right organ into the right recipient. But the evolution of matching donors and recipients above and beyond blood type and body size has not eliminated death on the waiting list, as the availability of deceased organ donors continues to lag behind the number of those waiting. Thus, the use of live organ donors has further expanded the donor pool. The use of an organ from a living donor has roots >50 years old. Doctor Joseph Murray performed a successful kidney transplant from 1 twin brother to another in 1954. In 2006, nearly 38% of all kidney transplants were from live donors.1The Organ Procurement and Transplantation Network, 2003. Available at: www.optn.org/latestData/rptData.asp. Accessed October 13, 2007.Google Scholar The use of live donors for liver transplants is a more recent, although less common, event. In 2006, 4.3% of liver transplants in this country were performed using a live donor.1The Organ Procurement and Transplantation Network, 2003. Available at: www.optn.org/latestData/rptData.asp. Accessed October 13, 2007.Google Scholar Three major questions regarding live donor liver transplantation (LDLT) must be the source of ongoing study (Table 1): (1) Will a recipient live after a live donor transplant? (2) Does living donor transplantation decrease the risk of death versus waiting for a deceased organ donor? (3) Can the procedure be performed to ensure the safety and well-being of the donor? Although each question is unique, these questions are nonetheless interrelated, particularly as a transplant recipient and a potential living donor consider the option of LDLT. For example, a potential recipient would likely not consider a LDLT if there were a significant risk to the life and health of the donor. Likewise, if the donor procedure was simple and safe, but posttransplant survival rates were significantly lower than those in deceased donor recipients, further discussion would be unnecessary. To answer questions regarding LDLT, the National Institutes of Health funded the Adult-to-Adult Living Donor Transplantation Retrospective Cohort Study (A2ALL) in 2002. Nine centers across the country were included with the primary objective of answering the question of survival benefit. In this issue of Gastroenterology, the A2ALL group presents data regarding the effect of living donor transplantation on wait list mortality.3Berg C.L. Gillespie B.W. Merion R.M. et al.Improvement in survival associated with adult-to-adult living donor liver transplantation.Gastroenterology. 2007; 133: 1806-1813Abstract Full Text Full Text PDF PubMed Scopus (152) Google Scholar The group studied 807 patients who presented with ≥1 potential living donor candidate. Patients with acute liver failure were not included in the study. The study followed those who ultimately received a LDLT and compared their survival with those who presented with a potential living donor candidate but did not receive a LDLT. Patients in the latter group subsequently received a deceased donor transplant, continued to wait for the appropriate deceased donor organ, or died on the waiting list. The study shows that those who received a LDLT had improved survival when compared with those presenting with a potential donor, but did not receive a LDLT. Survival rates in those receiving a LDLT were similar to those receiving a deceased donor transplant. Furthermore, early retransplants (<3 weeks after the initial transplant) were more common in the living donor recipients. Survival rates in the living donor recipients improved and early retransplants decreased when the transplant center volume exceeded 20 living donor transplants. Thus, center experience is a pivotal factor in survival after LDLT. Center experience may have had an effect on the volume of patients studied over time at the A2ALL centers. An increase in the percentage of patients studied was observed from 1998, the first year patients were enrolled, up to the implementation of MELD in 2002. After the implementation of MELD, the percentage of patients undergoing LDLT decreased from 35% to 19% of the total, and those presenting with a potential live donor, but not receiving a LDLT, decreased from 36% to 30%. One can only speculate about the reasons for this pattern. LDLT was a novel approach initially, and met with great enthusiasm; perhaps awareness led to more patients who presented with potential donors, more of whom were unacceptable. Perhaps this enthusiasm waned over time, particularly if donor complications occurred. The implementation of MELD led to allocation of deceased donor organs to sicker patients, possibly decreasing the need for LDLT. Finally, the effect of center experience cannot be discounted. Experience with technical issues and donor selection may have led to more stringent criteria for recipients and donors. One potential flaw in this study is selection bias. It should be borne in mind those patients investigated presented with ≥1 potential living donor. Many patients are never even considered as a living donor recipient for a variety of reasons. Prior operations with subsequent adhesions or anatomic variants that potentially increase the complexity of transplantation with a deceased donor, much less the added complexity of a live donor, can make LDLT untenable. Donor issues, such as underlying medical conditions, obesity with or without hepatic steatosis, and previous operations increase risk for both the donor and the recipient. Imagine the following scenario: a 60-year-old, 5’2” tall, 100-pound woman with primary biliary cirrhosis shows up with her “potential” donor, her 67-year-old, 5’3” tall, 220-pound, tobacco-dependent, diabetic sister with coronary artery disease. An appropriate live liver donor? No, but a “potential” donor, just the same. The point is that recipients and donors may be deemed inappropriate after a history and physical examination. The authors state this only accounted for 21% of those in the comparison group; however, this does raise the question of whether including these patients in the analysis is appropriate. Specifically, because the potential donor was unacceptable “at the door,” does this affect the comparison group by shifting patients who never really had a chance for LDLT into this group? Further interrogation of the comparison group reveals those receiving a LDLT had lower MELD scores, were significantly younger, had better occupational histories and functional status, and were more likely to be female. Although these issues may influence the analysis, perhaps the process of LDLT itself engenders selection bias. For example, only 10% of potential liver transplant recipients at these centers even had a potential liver donor. Previous studies have shown only 30% of donors are deemed acceptable,4Trotter J.F. Wachs M. Trouillot T. et al.Evaluation of 100 patients for living donor liver transplantation.Liver Transpl. 2000; 6: 290-295Crossref PubMed Scopus (110) Google Scholar although 48.2% received a LDLT in this study. With such a highly selected population, one would assume survival rates would be better than waiting for a deceased donor. Nevertheless, this study is the first to demonstrate data supporting such a conclusion. Unfortunately, LDLT accounts for only 3%–5% of all transplants. Does every organ help? Of course. However, more information is needed about the long-term outcomes of both recipients and donors before patients can accept this process as a safe and viable alternative to deceased donor transplantation. Although this study focused on the effect of LDLT on wait-list mortality, donor safety cannot be ignored. Such follow-up, ideally in the form of a national database, will likely require federal funding, owing to the enormity of the project. Many live donors move out of the area or refuse follow-up care owing to expense and the apparent lack of long-term complications. Only detailed follow-up and analysis, however, will answer the important questions regarding long-term complications. Data on donor safety are of paramount importance; however, many willing donors may not donate because of the financial disincentives associated with the procedure. Live liver donors frequently are away from work for 4–8 weeks. The Organ Donor Leave Act from 1999 guarantees pay for 30 days for federal employees after organ donation. Many states and corporations have similar programs. However, the potential salary loss surrounding donor surgery may not be the end of financial issues. After organ donation, many donors may become “uninsurable” owing to this new “preexisting” condition. As crucial as donor safety is, financial hardship interfering and even preventing live organ donation is absurd. Perhaps automatic eligibility for lifetime federal or state health care benefits, when needed, is required for these heroic efforts. The answers to these questions are not easy. This study shows, for the first time, that having a LDLT does lead to a survival advantage when compared with those with a potential living donor who do not have a LDLT. The transplant community, led by the A2ALL group, needs to continue to refine all aspects of LDLT, from donor and recipient selection to long-term follow-up, with the understanding that ongoing analysis is the only way important questions can be answered and those answers applied to the care of potential transplant recipients and live organ donors. Improvement in Survival Associated With Adult-to-Adult Living Donor Liver TransplantationGastroenterologyVol. 133Issue 6PreviewBackground & Aims: More than 2000 adult-to-adult living donor liver transplantations (LDLT) have been performed in the United States, yet the potential benefit to liver transplant candidates of undergoing LDLT compared with waiting for deceased donor liver transplantation (DDLT) is unknown. The aim of this study was to determine whether there is a survival benefit of adult LDLT. Methods: Adults with chronic liver disease who had a potential living donor evaluated from January 1998 to February 2003 at 9 university-based hospitals were analyzed. Full-Text PDF