Recent Advances in Liver Transplantation
2003; Elsevier BV; Volume: 78; Issue: 2 Linguagem: Inglês
10.4065/78.2.197
ISSN1942-5546
AutoresRussell H. Wiesner, Jorge Rakela, Michael B. Ishitani, David C. Mulligan, James R. Spivey, Jeffery L. Steers, Ruud A. F. Krom,
Tópico(s)Liver Disease Diagnosis and Treatment
ResumoAdvances in liver transplantation continue to evolve but are hampered by continued increasing shortages in donor organs. This has resulted in a high incidence of patients dying while on the United Network for Organ Sharing waiting list. Indeed, we continue to assess ways of expanding the donor pool by using marginal donors, living donor liver transplantation, split liver transplantation, domino transplantation, and hepatic support systems to prolong survival long enough for the patient to undergo liver transplantation. Changes in the liver allocation policy to reduce the number of people dying while waiting for an organ are discussed. Implementation of the model for endstage liver disease allocation system should help alleviate the problem of increasing deaths of patients while on the waiting list. Recurrent disease, particularly recurrent hepatitis C, continues to be a major problem, and effective therapy is needed to prevent both progression of hepatitis C and recurrence in the graft and avoid retransplantation. The use of pegylated interferon in combination with ribavirin holds promise for improving the success in overcoming recurrent hepatitis C. Finally, advances in immunosuppression have reduced the incidence of acute cellular rejection and chronic rejection. However, these therapies have been fraught with metabolic complications that are now affecting quality of life and long-term survival. Tailoring immunosuppressive regimens to the individual patient is discussed. Advances in liver transplantation continue to evolve but are hampered by continued increasing shortages in donor organs. This has resulted in a high incidence of patients dying while on the United Network for Organ Sharing waiting list. Indeed, we continue to assess ways of expanding the donor pool by using marginal donors, living donor liver transplantation, split liver transplantation, domino transplantation, and hepatic support systems to prolong survival long enough for the patient to undergo liver transplantation. Changes in the liver allocation policy to reduce the number of people dying while waiting for an organ are discussed. Implementation of the model for endstage liver disease allocation system should help alleviate the problem of increasing deaths of patients while on the waiting list. Recurrent disease, particularly recurrent hepatitis C, continues to be a major problem, and effective therapy is needed to prevent both progression of hepatitis C and recurrence in the graft and avoid retransplantation. The use of pegylated interferon in combination with ribavirin holds promise for improving the success in overcoming recurrent hepatitis C. Finally, advances in immunosuppression have reduced the incidence of acute cellular rejection and chronic rejection. However, these therapies have been fraught with metabolic complications that are now affecting quality of life and long-term survival. Tailoring immunosuppressive regimens to the individual patient is discussed. As we begin the 21st century, liver transplantation is the treatment of choice for patients with acute fulminant hepatic failure, end-stage chronic liver disease, and certain metabolic liver diseases for which no alternative therapies are available. One-year patient survival approaches 90%, and a 3-year survival of 80% is achieved at many leading medical centers in the United States. In addition to longer survival, many liver transplant recipients are now experiencing improved quality of life, including resumption of active employment and reproductive capacity.12001 Annual Report of the U.S. Organ Procurement and Transplantation Network and the Scientific Registry for Transplant Recipients: Transplant Data 1991-2000. Rockville, Md: Dept of Health and Human Services, Health Resources and Services Administration, Office of Special Programs, Division of Transplantation. United Network for Organ Sharing; and Ann Arbor, Mich: University Renal Research and Education Association, Richmond, Va2001Google Scholar, 2United Network for Organ Sharing. Policy 3.6. Allocation of livers.Available at: www.unos.org/Google Scholar, 3Gross CR Malinchoc M Kim WR et al.Quality of life before and after liver transplantation for cholestatic liver disease.Hepatology. 1999; 29: 356-364Crossref PubMed Scopus (105) Google Scholar, 4Ratcliffe J Longworth L Young T Bryan S Burroughs A Buxton M Cost-Effectiveness of Liver Transplantation Team Assessing health-related quality of life pre- and post-liver transplantation: a prospective multicenter trial.Liver Transpl. 2002; 8: 263-270Crossref PubMed Scopus (68) Google Scholar Despite these advances, liver transplantation faces several major challenges. The most important of these is dealing with the donor shortage.12001 Annual Report of the U.S. Organ Procurement and Transplantation Network and the Scientific Registry for Transplant Recipients: Transplant Data 1991-2000. Rockville, Md: Dept of Health and Human Services, Health Resources and Services Administration, Office of Special Programs, Division of Transplantation. United Network for Organ Sharing; and Ann Arbor, Mich: University Renal Research and Education Association, Richmond, Va2001Google Scholar As the hepatitis C virus (HCV) epidemic develops, the demand for liver transplants could increase as much as 5-fold. Furthermore, recurrent disease, in particular recurrent hepatitis C, has evolved as a leading cause of late graft failure and a major indication for retransplantation.5Testa G Crippin JS Netto GJ et al.Liver transplantation for hepatitis C: recurrence and disease progression in 300 patients.Liver Transpl. 2000; 6: 553-561Crossref PubMed Google Scholar, 6Berenguer M Ferrell L Watson J et al.HCV-related fibrosis progression following liver transplantation: increase in recent years.J Hepatol. 2000; 32: 673-684Abstract Full Text Full Text PDF PubMed Scopus (507) Google Scholar, 7Rosen HR Retransplantation for hepatitis C: implications of different policies.Liver Transpl. 2000; 6: S41-S46Crossref Google Scholar Complications related to prolonged immunosuppressive therapy have also occurred, with many patients developing diabetes, hypercholesterolemia, progressive renal insufficiency, hypertension, and osteoporosis. Furthermore, all liver transplant recipients remain at increased risk for major infections and development of de novo malignancies, the major causes of late death.8Abbasoglu O Levy MF Brkic BB et al.Ten years of liver transplantation: an evolving understanding of late graft loss.Transplantation. 1997; 64: 1801-1807Crossref PubMed Scopus (96) Google Scholar, 9Sheiner PA Magliocca JF Bodian CA et al.Long-term medical complications in patients surviving ≥ 5 years after liver transplant.Transplantation. 2000; 69: 781-789Crossref PubMed Google Scholar, 10Stegall MD Everson G Schroter G Bilir B Karrer F Kam I Metabolic complications after liver transplantation: diabetes, hypercholesterolemia, hypertension, and obesity.Transplantation. 1995; 60: 1057-1060PubMed Google Scholar, 11Canzanello VJ Schwartz L Taler SJ et al.Evolution of cardiovascular risk after liver transplantation: a comparison of cyclosporine A and tacrolimus (FK506).Liver Transpl Surg. 1997; 3: 1-9Crossref PubMed Google Scholar, 12Fisher NC Nightingale PG Gunson BK Lipkin GW Neuberger JM Chronic renal failure following liver transplantation: a retrospective analysis.Transplantation. 1998; 66: 59-66Crossref PubMed Scopus (216) Google Scholar, 13Gonwa TA Mai ML Melton LB et al.End-stage renal disease (ESRD) after orthotopic liver transplantation (OLTX) using calcineurin-based immunotherapy: risk of development and treatment.Transplantation. 2001; 72: 1934-1939Crossref PubMed Google Scholar Transplant centers encounter an increasing number of cases of hepatocellular cancer, particularly in patients who have chronic hepatitis C with cirrhosis. Recent studies have documented a marked increase in the incidence of hepato-cellular cancer during the past decade,14El-Serag HB Mason AC Rising incidence of hepatocellular carcinoma in the United States.N Engl J Med. 1999; 340: 745-750Crossref PubMed Scopus (2060) Google Scholar and we will almost certainly see a further increase in the next decade related to the HCV epidemic. Additionally, we are challenged by patients who present with acute fulminant hepatitis who have only hours to live and are in need of a lifesaving liver transplantation. The development of bioartificial liver support systems appears to have tremendous potential in providing a bridge to liver transplantation in this subgroup of patients.15Riordan SM Williams R Acute liver failure: targeted artificial and hepatocyte-based support of liver regeneration and reversal of multiorgan failure.J Hepatol. 2000; 32: 63-76Abstract Full Text PDF Google Scholar Today, more than 18,000 patients are on the United Network for Organ Sharing (UNOS) list waiting for a liver. However, in the past 5 years, the number of cadaver organs available for liver transplantation in the United States has remained stable at approximately 4600 per year (Figure 1).12001 Annual Report of the U.S. Organ Procurement and Transplantation Network and the Scientific Registry for Transplant Recipients: Transplant Data 1991-2000. Rockville, Md: Dept of Health and Human Services, Health Resources and Services Administration, Office of Special Programs, Division of Transplantation. United Network for Organ Sharing; and Ann Arbor, Mich: University Renal Research and Education Association, Richmond, Va2001Google Scholar With an ever-increasing number of patients on the waiting list and a stable number of available cadaver donors, the number of patients who die while on the waiting list had increased steadily but plateaued in recent years, with approximately 1800 potential liver recipients dying while on the waiting list in the year 2000.12001 Annual Report of the U.S. Organ Procurement and Transplantation Network and the Scientific Registry for Transplant Recipients: Transplant Data 1991-2000. Rockville, Md: Dept of Health and Human Services, Health Resources and Services Administration, Office of Special Programs, Division of Transplantation. United Network for Organ Sharing; and Ann Arbor, Mich: University Renal Research and Education Association, Richmond, Va2001Google Scholar In addition, numerous patients are removed from the UNOS waiting list because they become too ill or experience tumor growth or spread, making them ineligible for liver transplantation. Thus, the success of liver transplantation has increased the demand, which has resulted in a marked discrepancy between the number of patients waiting for a liver and the number of available organs. During the past several years, a number of innovative and creative techniques have been developed to deal with the donor shortage (Table 1). In the past, older donors (>55 years of age), those with fatty infiltration, those with diabetes mellitus, and those who were HCV or hepatitis B virus (HBV) positive were typically excluded but are now termed marginal donors. In more recent years, organs from marginal donors have been used with increasing success. Several studies have shown that organs from older donors (>50 years of age) or from those who have mild to moderate fatty infiltration can be used with good results if cold ischemia time is minimized.16Hoofnagle JH Lonbardero M Zetterman RK et al.Donor age and outcome of liver transplantation.Hepatology. 1996; 24: 89-96Crossref PubMed Google Scholar, 17Yersiz H Shaked A Olthoff K et al.Correlation between donor age and the pattern of liver graft recovery after transplantation.Transplantation. 1995; 60: 790-794PubMed Google Scholar, 18Washburn WK Johnson LB Lewis WD Jenkins RL Graft function and outcome of older (> or = 60 years) donor livers.Transplantation. 1996; 61: 1062-1066Crossref PubMed Scopus (66) Google Scholar, 19Emre S Schwartz ME Altaca G et al.Safe use of hepatic allografts from donors older than 70 years.Transplantation. 1996; 62: 62-65Crossref PubMed Scopus (109) Google Scholar, 20Jimenez Romero C Moreno Gonzalez E Colina Ruiz F et al.Use of octogenarian livers safely expands the donor pool.Transplantation. 1999; 68: 572-575Crossref PubMed Scopus (60) Google Scholar Organs from donors who are HBV or HCV positive are now used in recipients who have HBV or HCV, respectively, as their underlying liver disease. Recent studies have shown that transplanting organs from HCV-positive donors in patients with HCV does not appear to have an adverse effect.21Vargas HE Laskus T Wang LF et al.Outcome of liver transplantation in hepatitis C virus-infected patients who received hepatitis C virus-infected grafts.Gastroenterology. 1999; 117: 149-153Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar Similarly, studies have suggested that an organ from a hepatitis B core antibody-positive donor, which can subsequently cause de novo hepatitis B infection in the liver recipient, can be used if prophylactic treatment with lamivudine and hepatitis B immune globulin (HBIG) is administered.22Dodson SF Bonham CA Geller DA Cacciarelli TV Rakela J Fung JJ Prevention of de novo hepatitis B infection in recipients of hepatic allografts from anti-HBc positive donors.Transplantation. 1999; 68: 1058-1061Crossref PubMed Scopus (125) Google ScholarTable 1Resources Available for Expanding the Donor Pool Marginal donors Older donors (>50 y)Donors with fatty infiltrationHepatitis B and C virus-positive donorsSplit liver transplantsDomino transplantsLiving donorsXenografts Open table in a new tab Other ways to deal with the donor shortage include split liver transplantation in which a cadaver liver is split into 2 pieces, with the right lobe usually being used for an adult recipient and the left lobe or left lateral segment being used for a small adult or a pediatric recipient.23Rogiers X Malago M Gawad K et al.In situ splitting of cadaveric livers: the ultimate expansion of a limited donor pool.Ann Surg. 1996; 224: 331-339Crossref PubMed Scopus (225) Google Scholar, 24Busuttil RW Goss JA Split liver transplantation.Ann Surg. 1999; 229: 313-321Crossref PubMed Google Scholar, 25Rela M Vougas V Muiesan P et al.Split liver transplantation: King's College Hospital experience.Ann Surg. 1998; 227: 282-288Crossref PubMed Scopus (121) Google Scholar, 26Ghobrial RM Yersiz H Farmer DG et al.Predictors of survival after in vivo split liver transplantation: analysis of 110 consecutive patients.Ann Surg. 2000; 232: 312-323Crossref PubMed Scopus (89) Google Scholar, 27Sindhi R Rosendale J Mundy D et al.Impact of segmental grafts on pediatric liver transplantation—a review of the United Network for Organ Sharing Scientific Registry data (1990-1996).J Pediatr Surg. 1999; 34: 107-110Abstract Full Text PDF PubMed Scopus (64) Google Scholar, 28Sommacale D Farges O Ettorre GM et al.In situ split liver transplantation for two adult recipients.Transplantation. 2000; 69: 1005-1007Crossref PubMed Google Scholar However, the optimal technique used to split the liver is controversial. At least 1 center showed a marked advantage for in vivo splitting vs ex vivo splitting in regard to overall out-comes.28Sommacale D Farges O Ettorre GM et al.In situ split liver transplantation for two adult recipients.Transplantation. 2000; 69: 1005-1007Crossref PubMed Google Scholar, 29Azoulay D Castaing D Adam R et al.Split-liver transplantation for two adult recipients: feasibility and long-term outcomes.Ann Surg. 2001; 233: 565-574Crossref PubMed Scopus (86) Google Scholar The advantage of split liver transplantation is that 2 patients receive transplants from 1 donor. The disadvantage is that split liver transplantation appears to be associated with decreased graft survival and an increased number of biliary complications compared with whole liver transplantation. However, data are accumulating that show that split liver transplantation should be used for select patients who are UNOS 2B status (model for end-stage liver disease [MELD] score =24) (see subsequent section on liver allocation policy for further details) and should not be used or should be used cautiously in patients with more severe underlying liver diseases, such as those who are UNOS status 1 or those who have a MELD score of 25 or higher. Split liver transplantation is technically demanding, and the results vary widely among liver transplant centers, which may be related to a distinct learning curve. Nonetheless, split liver transplantation is an important option for expanding the donor pool, may be potentially beneficial for pediatric patients, and could potentially lead to decreased waiting times for both pediatric and adult recipients. Another means of increasing the donor pool is domino liver transplantation.30Dyer PA Bobrow M Unrelated Live Transplant Regulatory Authority (ULTRA). Domino hepatic transplantation using the liver from a patient with familial amyloid polyneuropathy [letter].Transplantation. 1999; 67: 1202Crossref PubMed Scopus (3) Google Scholar In this situation, a patient with familial amyloidosis (a disease in which the liver produces a mutated transthyretin gene molecule that accumulates in blood vessels, nerve tissue, and other organs) receives a liver transplant from a cadaver donor. This patient's liver in turn is procured and transplanted into an elderly recipient. Since symptoms related to familial amyloidosis develop over a period of 20 to 30 years, short-term follow-up data suggest that a liver from a patient with familial amyloid disease can be used for liver transplantation without early adverse effects. A major advance that has increased the donor pool is living donor liver transplantation.31Wachs ME Bak TE Karrer FM et al.Adult living donor liver transplantation using a right hepatic lobe.Transplantation. 1998; 66: 1313-1316Crossref PubMed Google Scholar, 32Marcos A Right-lobe living donor liver transplantation.Liver Transpl. 2000; 6: S59-S63Crossref Google Scholar Living donor liver transplantation was first reported in 1990.33Strong RW Lynch SV Ong TH Matsunami H Koido Y Balderson GA Successful liver transplantation from a living donor to her son.N Engl J Med. 1990; 322: 1505-1507Crossref PubMed Google Scholar A left lateral segment (segment 2-3) of an adult liver was resected and grafted into a child. This procedure has been tremendously successful, with patient and graft survival approaching that achieved with cadaver donor liver transplantation.34Reding R de Goyet Jde V Delbeke I et al.Pediatric liver transplantation with cadaveric or living related donors: comparative results in 90 elective recipients of primary grafts.J Pediatr. 1999; 134: 280-286Abstract Full Text Full Text PDF PubMed Google Scholar Adult to pediatric live donor liver transplantation is a standard of care at many pediatric liver transplant centers worldwide. Living donor adult-to-adult liver transplantation was first reported in 1994.35Trotter JF Wachs M Everson GT Kam I Adult-to-adult transplantation of the right hepatic lobe from a living donor.N Engl J Med. 2002; 346: 1074-1082Crossref PubMed Scopus (315) Google Scholar In this procedure, the right lobe (segment 5 and 8), representing 60% to 65% of the liver, is resected from the donor and grafted into the recipient. Because of the ever-increasing number of patients on the UNOS list waiting for a liver transplant, this procedure has evolved rapidly in the United States, with more than 500 adult-to-adult liver transplantations performed in 2001 (Figure 2).36Testa G Malago M Nadalin S et al.Right-liver living donor transplantation for decompensated end-stage liver disease.Liver Transpl. 2002; 8: 340-346Crossref PubMed Scopus (58) Google Scholar Adult-to-adult living donor liver transplantation is also popular in Japan because of the lack of cadaver donors due to cultural differences in the definition of brain death. Adult-to-adult live donor liver transplantation has been highly successful, particularly when used in nonurgent situations, such as in patients previously designated UNOS status 2B or 3 or those with a MELD score lower than 25. This procedure has also played an important role in transplant recipients with hepatocellular cancer who often wait 1 1/2 to 2 years designated as UNOS 2B status and then have disease progression and metastasis, eliminating them as candidates for a liver transplant. Results have been less favorable when used in urgent situations, such as in patients previously designated UNOS status 1 and 2A or those with a MELD score greater than 25. Although living donor liver transplantation in adults is attractive, the procedure is technically demanding and has several drawbacks.37Shiffman ML Brown Jr, RS Olthoff KM et al.Living donor liver transplantation: summary of a conference at The National Institutes of Health.Liver Transpl. 2002; 8: 174-188Crossref PubMed Scopus (97) Google Scholar, 38Beavers KL Sandler RS Shrestha R Donor morbidity associated with right lobectomy for living donor liver transplantation to adult recipients: a systematic review.Liver Transpl. 2002; 8: 110-117Crossref PubMed Scopus (137) Google Scholar, 39Surman OS The ethics of partial-liver donation.N Engl J Med. 2002; 346: 1038Crossref PubMed Scopus (120) Google Scholar First, at present, only one third of liver recipients can identify a potential donor who becomes a candidate after undergoing evaluation. Second, although the risk of death for the donor has not been defined, at least 2 deaths have been reported in living liver donors in the United States.39Surman OS The ethics of partial-liver donation.N Engl J Med. 2002; 346: 1038Crossref PubMed Scopus (120) Google Scholar Furthermore, a 20% to 30% morbidity rate has been experienced in living donors, directly related to the hepatic resection. A third drawback relates to potential coercion and the apparent conflict of interest.37Shiffman ML Brown Jr, RS Olthoff KM et al.Living donor liver transplantation: summary of a conference at The National Institutes of Health.Liver Transpl. 2002; 8: 174-188Crossref PubMed Scopus (97) Google Scholar, 39Surman OS The ethics of partial-liver donation.N Engl J Med. 2002; 346: 1038Crossref PubMed Scopus (120) Google Scholar Finally, many medical centers have reported substantial donor costs that appear to exceed the costs associated with procuring a cadaver donor. Despite these drawbacks, graft survival is comparable to that achieved with cadaver donors in younger recipients but is significantly decreased in older recipients (>50 years of age) (Figure 3, left).12001 Annual Report of the U.S. Organ Procurement and Transplantation Network and the Scientific Registry for Transplant Recipients: Transplant Data 1991-2000. Rockville, Md: Dept of Health and Human Services, Health Resources and Services Administration, Office of Special Programs, Division of Transplantation. United Network for Organ Sharing; and Ann Arbor, Mich: University Renal Research and Education Association, Richmond, Va2001Google Scholar Similarly, with use of living donors, graft survival decreases significantly with donor age compared with use of cadaver donors (Figure 3, right). Furthermore, most series report a modest increase in the number of biliary complications and a slightly increased retransplantation rate. In a recent survey, most US liver transplantation centers indicated that they have either done right lobe living donor transplantation or plan to perform this procedure in the future.37Shiffman ML Brown Jr, RS Olthoff KM et al.Living donor liver transplantation: summary of a conference at The National Institutes of Health.Liver Transpl. 2002; 8: 174-188Crossref PubMed Scopus (97) Google Scholar The overwhelming reason is the continued donor shortage and the ever-increasing number of patients on the UNOS liver waiting list. However, many believe that living donor transplantation may further expand indications for liver transplantation, thus nullifying some of its potential positive effect on the donor shortage. During the next several years, adult living donor liver transplantation should continue to evolve as it becomes more common. A further development that has helped in dealing with the donor shortage in patients who present with acute fulminant hepatitis is the use of hepatic support systems.15Riordan SM Williams R Acute liver failure: targeted artificial and hepatocyte-based support of liver regeneration and reversal of multiorgan failure.J Hepatol. 2000; 32: 63-76Abstract Full Text PDF Google Scholar These devices use either a dialysis-type method or columns of hepatocytes from pigs or humans. The major goal of treating patients with acute fulminant hepatitis is to prevent the development of cerebral edema and brainstem herniation, thus providing a bridge to liver transplantation. In addition, theoretically, a hepatic support device could allow time for hepatic regeneration, thus potentially excluding the need for liver transplantation. Finally, xenografting has received much press in recent years; however, clinical use of xenografts does not appear feasible at this time.40Lambrigts D Sachs DH Cooper DK Discordant organ xeno-transplantation in primates: world experience and current status.Transplantation. 1998; 66: 547-561Crossref PubMed Scopus (142) Google Scholar, 41Harland RC Platt JL Prospects for xenotransplantation of the liver.J Hepatol. 1996; 25: 248-258Abstract Full Text PDF PubMed Scopus (11) Google Scholar Gene therapy has been able to deal with hyperacute rejection in xenografts; however, vascular rejection has been difficult to control and is the major challenge facing xenotransplantation. In addition, transmission of infectious viruses across species remains a potential concern.41Harland RC Platt JL Prospects for xenotransplantation of the liver.J Hepatol. 1996; 25: 248-258Abstract Full Text PDF PubMed Scopus (11) Google Scholar, 42Allan JS Xenograft transplantation and the infectious disease conundrum.ILAR J. 1995; 37: 37-48Crossref Google Scholar, 43Michaels MG Simmons RL Xenotransplant-associated zoo-noses: strategies for prevention.Transplantation. 1994; 57: 1-7Crossref PubMed Google Scholar, 44Ye Y Niekrasz M Kosanke S et al.The pig as a potential organ donor for man: a study of potentially transferable disease from donor pig to recipient man.Transplantation. 1994; 57: 694-703Crossref PubMed Google Scholar, 45Patience C Takeuchi Y Weiss RA Infection of human cells by an endogenous retrovirus of pigs.Nat Med. 1997; 3: 282-286Crossref PubMed Scopus (765) Google Scholar An alternative approach to a decrease in the death of patients on the UNOS waiting list is to change the current allocation policy. A change in the liver allocation policy has been spurred by the Health and Human Services final rule mandate that provides the following guidelines: (1) organs should be allocated to transplant candidates in the order of medical urgency, (2) the role of waiting times should be minimized, and (3) attempts should be made to avoid futile transplantations and promote efficient use of the scarce donor organs.46Committee on Organ Procurement and Transplantation Policy Organ Procurement and Transplantation: Assessing Current Policies and the Potential Impact of the DHHS Final Rule. National Academy Press, Washington, DC1999: 61-90Google Scholar Previously, the UNOS liver allocation policy was based on the Child-Turcotte-Pugh (CTP) score and on waiting time.2United Network for Organ Sharing. Policy 3.6. Allocation of livers.Available at: www.unos.org/Google Scholar During the past few years, several limitations have been identified with both the UNOS allocation scheme and the CTP score. The most important shortcoming of the UNOS allocation policy was that it defined only 3 categories of disease severity for patients with chronic end-stage liver disease: status 3 (CTP score =7), status 2B (CTP score =10), and status 2A (CTP score >10) in the intensive care unit and less than 7 days to live.2United Network for Organ Sharing. Policy 3.6. Allocation of livers.Available at: www.unos.org/Google Scholar With only 3 categories of disease severity, waiting time had become an extremely important factor, serving as a tiebreaker within each category. This was particularly a problem for patients classified as status 2B, the largest group of patients waiting for liver transplantation, who had a broad range of liver disease severity.47Wiesner RH McDiarmid SV Kamath PS et al.MELD and PELD: application of survival models to liver allocation.Liver Transpl. 2001; 7: 567-580Crossref PubMed Scopus (416) Google Scholar This problem was further magnified by the fact that the waiting time accrued by patients classified as status 3 while on the waiting list was applied as they advanced to status 2B. Since waiting time was shown in 2 studies not to correlate with death while on the waiting list,2United Network for Organ Sharing. Policy 3.6. Allocation of livers.Available at: www.unos.org/Google Scholar, 48Freeman RB Rohrer RJ Katz E et al.Preliminary results of a liver allocation plan using a continuous medical severity score that de-emphasizes waiting time.Liver Transpl. 2001; 7: 173-178Crossref PubMed Scopus (54) Google Scholar deemphasizing waiting time as an organ allocation factor seemed appropriate. Although the UNOS allocation scheme clearly failed to prioritize liver allocation based on medical urgency, the CTP score itself was found to have limited usefulness as an index of disease severity. These drawbacks were primarily due to limited discriminant ability and variability of the CTP score. First, the CTP score has a limited number of disease categories. Second, the CTP score is limited by its inability to discriminate disease severity among the sickest patients. For example, patients with a bilir
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