LIVER TRANSPLANTATION 20:1290–1292, 2014
EDITORIAL
Living Donor Liver Transplantation: Alive and Well Michael D. Leise Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN Received September 8, 2014; accepted September 10, 2014.
See Article on Page 1347 Deceased donor liver transplantation (DDLT) and living donor liver transplantation (LDLT) are thought to offer equivalent posttransplant survival, although, of course, there are no, nor will there ever be, randomized controlled trials to prove or disprove this point. The Adultto-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) consortium has played a pivotal role in advancing the knowledge base about risks, benefits, and outcomes for donors and recipients undergoing donation surgery and LDLT in North America.1 It has provided needed information that cannot be adequately gleaned from the North American single-center studies that preceded it. Outside a recent large United Network for Organ Sharing (UNOS) database study, contemporary data that directly compare outcomes for LDLT and DDLT are rare, especially when it comes to hospital-level metrics such as the length of admission, readmission, and costs.2 To answer the question of how real-world outcomes of adult LDLT compare with those of DDLT in contemporary patients, Hoehn et al.3 performed a retrospective analysis by linking data from the Scientific Registry of Transplant Recipients Standard Analysis File and the University HealthSystem Consortium. The University HealthSystem Consortium is an alliance of 118 academic medical centers that collects demographic, financial, International Classification of Diseases (9th edition), and procedural data. Between 2007 and 2012, 14,282 patients receiving DDLT at 62 centers and 715 LDLT recipients at 35 centers were identified. Propensity matching (1:1) by the variables
of age, Model for End-Stage Liver Disease (MELD) score, and pretransplant location (intensive care unit, ward, or outpatient) was used to adjust for the underlying variables that may factor into the decision for a particular patient to receive DDLT (n 5 708) versus LDLT (n 5 708). The LDLT recipients were more likely to be white females with a lower body mass index and a younger age ( 20 LDLT cases was associated with significantly lower graft failure; this is consistent with the recent 10-year UNOS analysis.1 The findings of marginally longer hospital stays and significantly higher readmission rates for LDLT recipients are novel for contemporary patients but are somewhat overshadowed by the survival outcomes. A higher likelihood of rehospitalization after LDLT was also noted in an older era.4 Direct costs for the 2 types of transplants were comparable (LDLT, $108,325; DDLT, $103,513). These novel hospital-level outcomes are an important contribution to the literature. There are several shortcomings to this analysis. The percentage of DDLT recipients who received deceased after circulatory determination of death (DCDD) organs was not stated, and results with and without DCDD would be important because of their inferior outcomes. Although the linkage of the 2 databases allows one to capture hospital-level outcomes, which is a worthy pursuit, the lack of complete data (43% of DDLTs and 63% of LDLTs performed during 20072012) jeopardizes the validity of the survival analysis. With respect to the propensity score, only a few variables were used in the propensity matching. Many other recipient factors (eg, serum sodium, ascites, hepatic encephalopathy, and life support) that reflect the severity of illness were not included in the propensity analysis, nor were positive prognostic factors such as cholestatic liver disease (diminished wait-list mortality and improved LDLT outcomes). Other important variables that were not included in the propensity analysis were the year of transplant, transplant center volume determined by volume of LDLT alone, donor age, and recipient height. Propensity scores should consider all potential confounding variables that could be related to the receipt of LDLT versus DDLT, and this was not the case for this analysis. It is likely that patients were intentionally selected to undergo LDLT on the basis of factors such as cholestatic liver disease (“other” category), better renal function, a lower likelihood of a MELD exception, and shorter height, and these factors were not captured in the propensity matching analysis. Another inherent limitation is the relative infrequency of high-MELD patients in the LDLT group, with only 17 having a MELD score 28. With these shortcomings in mind, the propensity score–matched cohort demonstrated that LDLT survival was comparable to DDLT survival, and this result is similar to findings by Goldberg et al.2 in the large 10-year UNOS/Organ Procurement and Transplantation Network analysis.
LEISE 1291
Additionally, it should be noted that this type of study does not fully capture any survival advantage for one type of transplant over the other. An analysis that evaluates all LDLT candidates for whom a potential donor has been worked up followed by a comparison of those who go on to receive LDLT versus DDLT is more appropriate.5 However, this was not the intent of the authors, and the data sets used do not allow for this type of analysis. Thus, conclusions can be drawn only about posttransplant survival. This contribution by Hoehn et al.3 adds credence to the notion that LDLT offers posttransplant survival outcomes similar to those of DDLT, but recipients may face higher 30-day readmission rates. It is known that LDLT recipients incur higher rates of biliary and vascular complications, so the higher readmission rate is not altogether surprising. For patients receiving LDLT at low-volume centers, mortality was significantly higher (12%-13%) than that for patients at high-volume centers (3%-5%), and high-volume centers had the lowest 30-day readmission rates, inhospital mortality, and total and intensive care unit lengths of stay. These results make a compelling case that liver transplant candidates who wish to pursue LDLT do so at high-volume centers. With the ever-increasing emphasis on value in health care, the LDLT-versus-DDLT cost differential is certainly an important consideration in the context of other important patient outcomes. It should be noted that, although costs are comparable for the 2 surgeries, the cost is reflective only of the index transplant recipient admission. Thus, the cost of living donor evaluations, surgery, and aftercare are not included in this analysis. Similarly, the organ acquisition costs are not included in this analysis. The cost of readmissions, given the difference in readmissions between the matched cohorts, is also an important aspect, as are the number of hospitalizations and other costs of pretransplant care for potential liver transplant recipients, which may be affected by access to LDLT. An evaluation that includes all of these costs would add to the discussion about value. In light of the continuously increasing median MELD score at transplant and these reassuring post-LDLT survival results, LDLT should be viewed as an essential option that can help to address organ scarcity and attenuate the morbidity with prolonged wait times.
REFERENCES 1. Olthoff KM, Merion RM, Ghobrial RM, Abecassis MM, Fair JH, Fisher RA, et al. Outcomes of 385 adult-toadult living donor liver transplant recipients: a report from the A2ALL consortium. Ann Surg 2005;242:314323. 2. Goldberg DS, French B, Abt PL, Olthoff K, Shaked A. Superior survival using living donors and donor-recipient matching using a novel living donor risk index. Hepatology; doi:10.1002/hep/27307. 3. Hoehn RS, Wilson GC, Wima K, Hohmann SF, Midura EF, Woodle ES, et al. Comparing living donor and deceased donor liver transplant: a matched national analysis from 2007-2012. Liver Transpl 2014;19.
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4. Merion RM, Shearon TH, Berg CL, Everhart JE, Abecassis MM, Shaked A, et al.; for A2ALL Study Group. Hospitalization rates before and after adult-to-adult living donor or deceased donor liver transplantation. Ann Surg 2010;251:542-549.
LIVER TRANSPLANTATION, November 2014
5. Berg CL, Gillespie BW, Merion RM, Brown RS Jr, Abecassis MM, Trotter JF, et al.; for A2ALL Study Group. Improvement in survival associated with adult-to-adult living donor liver transplantation. Gastroenterology 2007; 133:1806-1813.
EDITORIAL
Living Donor Liver Transplantation: Alive and Well Michael D. Leise Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN Received September 8, 2014; accepted September 10, 2014.
See Article on Page 1347 Deceased donor liver transplantation (DDLT) and living donor liver transplantation (LDLT) are thought to offer equivalent posttransplant survival, although, of course, there are no, nor will there ever be, randomized controlled trials to prove or disprove this point. The Adultto-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) consortium has played a pivotal role in advancing the knowledge base about risks, benefits, and outcomes for donors and recipients undergoing donation surgery and LDLT in North America.1 It has provided needed information that cannot be adequately gleaned from the North American single-center studies that preceded it. Outside a recent large United Network for Organ Sharing (UNOS) database study, contemporary data that directly compare outcomes for LDLT and DDLT are rare, especially when it comes to hospital-level metrics such as the length of admission, readmission, and costs.2 To answer the question of how real-world outcomes of adult LDLT compare with those of DDLT in contemporary patients, Hoehn et al.3 performed a retrospective analysis by linking data from the Scientific Registry of Transplant Recipients Standard Analysis File and the University HealthSystem Consortium. The University HealthSystem Consortium is an alliance of 118 academic medical centers that collects demographic, financial, International Classification of Diseases (9th edition), and procedural data. Between 2007 and 2012, 14,282 patients receiving DDLT at 62 centers and 715 LDLT recipients at 35 centers were identified. Propensity matching (1:1) by the variables
of age, Model for End-Stage Liver Disease (MELD) score, and pretransplant location (intensive care unit, ward, or outpatient) was used to adjust for the underlying variables that may factor into the decision for a particular patient to receive DDLT (n 5 708) versus LDLT (n 5 708). The LDLT recipients were more likely to be white females with a lower body mass index and a younger age ( 20 LDLT cases was associated with significantly lower graft failure; this is consistent with the recent 10-year UNOS analysis.1 The findings of marginally longer hospital stays and significantly higher readmission rates for LDLT recipients are novel for contemporary patients but are somewhat overshadowed by the survival outcomes. A higher likelihood of rehospitalization after LDLT was also noted in an older era.4 Direct costs for the 2 types of transplants were comparable (LDLT, $108,325; DDLT, $103,513). These novel hospital-level outcomes are an important contribution to the literature. There are several shortcomings to this analysis. The percentage of DDLT recipients who received deceased after circulatory determination of death (DCDD) organs was not stated, and results with and without DCDD would be important because of their inferior outcomes. Although the linkage of the 2 databases allows one to capture hospital-level outcomes, which is a worthy pursuit, the lack of complete data (43% of DDLTs and 63% of LDLTs performed during 20072012) jeopardizes the validity of the survival analysis. With respect to the propensity score, only a few variables were used in the propensity matching. Many other recipient factors (eg, serum sodium, ascites, hepatic encephalopathy, and life support) that reflect the severity of illness were not included in the propensity analysis, nor were positive prognostic factors such as cholestatic liver disease (diminished wait-list mortality and improved LDLT outcomes). Other important variables that were not included in the propensity analysis were the year of transplant, transplant center volume determined by volume of LDLT alone, donor age, and recipient height. Propensity scores should consider all potential confounding variables that could be related to the receipt of LDLT versus DDLT, and this was not the case for this analysis. It is likely that patients were intentionally selected to undergo LDLT on the basis of factors such as cholestatic liver disease (“other” category), better renal function, a lower likelihood of a MELD exception, and shorter height, and these factors were not captured in the propensity matching analysis. Another inherent limitation is the relative infrequency of high-MELD patients in the LDLT group, with only 17 having a MELD score 28. With these shortcomings in mind, the propensity score–matched cohort demonstrated that LDLT survival was comparable to DDLT survival, and this result is similar to findings by Goldberg et al.2 in the large 10-year UNOS/Organ Procurement and Transplantation Network analysis.
LEISE 1291
Additionally, it should be noted that this type of study does not fully capture any survival advantage for one type of transplant over the other. An analysis that evaluates all LDLT candidates for whom a potential donor has been worked up followed by a comparison of those who go on to receive LDLT versus DDLT is more appropriate.5 However, this was not the intent of the authors, and the data sets used do not allow for this type of analysis. Thus, conclusions can be drawn only about posttransplant survival. This contribution by Hoehn et al.3 adds credence to the notion that LDLT offers posttransplant survival outcomes similar to those of DDLT, but recipients may face higher 30-day readmission rates. It is known that LDLT recipients incur higher rates of biliary and vascular complications, so the higher readmission rate is not altogether surprising. For patients receiving LDLT at low-volume centers, mortality was significantly higher (12%-13%) than that for patients at high-volume centers (3%-5%), and high-volume centers had the lowest 30-day readmission rates, inhospital mortality, and total and intensive care unit lengths of stay. These results make a compelling case that liver transplant candidates who wish to pursue LDLT do so at high-volume centers. With the ever-increasing emphasis on value in health care, the LDLT-versus-DDLT cost differential is certainly an important consideration in the context of other important patient outcomes. It should be noted that, although costs are comparable for the 2 surgeries, the cost is reflective only of the index transplant recipient admission. Thus, the cost of living donor evaluations, surgery, and aftercare are not included in this analysis. Similarly, the organ acquisition costs are not included in this analysis. The cost of readmissions, given the difference in readmissions between the matched cohorts, is also an important aspect, as are the number of hospitalizations and other costs of pretransplant care for potential liver transplant recipients, which may be affected by access to LDLT. An evaluation that includes all of these costs would add to the discussion about value. In light of the continuously increasing median MELD score at transplant and these reassuring post-LDLT survival results, LDLT should be viewed as an essential option that can help to address organ scarcity and attenuate the morbidity with prolonged wait times.
REFERENCES 1. Olthoff KM, Merion RM, Ghobrial RM, Abecassis MM, Fair JH, Fisher RA, et al. Outcomes of 385 adult-toadult living donor liver transplant recipients: a report from the A2ALL consortium. Ann Surg 2005;242:314323. 2. Goldberg DS, French B, Abt PL, Olthoff K, Shaked A. Superior survival using living donors and donor-recipient matching using a novel living donor risk index. Hepatology; doi:10.1002/hep/27307. 3. Hoehn RS, Wilson GC, Wima K, Hohmann SF, Midura EF, Woodle ES, et al. Comparing living donor and deceased donor liver transplant: a matched national analysis from 2007-2012. Liver Transpl 2014;19.
1292 LEISE
4. Merion RM, Shearon TH, Berg CL, Everhart JE, Abecassis MM, Shaked A, et al.; for A2ALL Study Group. Hospitalization rates before and after adult-to-adult living donor or deceased donor liver transplantation. Ann Surg 2010;251:542-549.
LIVER TRANSPLANTATION, November 2014
5. Berg CL, Gillespie BW, Merion RM, Brown RS Jr, Abecassis MM, Trotter JF, et al.; for A2ALL Study Group. Improvement in survival associated with adult-to-adult living donor liver transplantation. Gastroenterology 2007; 133:1806-1813.
