LIVER TRANSPLANTATION 20:1347–1355, 2014
ORIGINAL ARTICLE
Comparing Living Donor and Deceased Donor Liver Transplantation: A Matched National Analysis From 2007 to 2012 Richard S. Hoehn,1 Gregory C. Wilson,1 Koffi Wima,1 Samuel F. Hohmann,2 Emily F. Midura,1 E. Steve Woodle,1 Daniel E. Abbott,1 Ashish Singhal,1 and Shimul A. Shah1 1 Cincinnati Research in Outcomes and Safety in Surgery, Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, OH; and 2University Health System Consortium and Department Health Systems Management, Rush University, Chicago, IL
A complete evaluation of living donor liver transplantation (LDLT) in the United States has been difficult because of the persistent low volume and the lack of adequate comparisons with deceased donor liver transplantation (DDLT). Recent reports have suggested outcomes equivalent to those for DDLT, but these studies did not adjust for differences in recipient selection. From a linkage between the University HealthSystem Consortium and Scientific Registry of Transplant Recipients databases, we identified 14,282 patients at 62 centers who underwent DDLT from 2007 to 2012 and 715 patients at 35 centers who underwent LDLT during the same period. Then, we performed 1:1 propensity score matching for 708 LDLT recipients based on age, Model for End-Stage Liver Disease (MELD) score, and pretransplant patient status. The median follow-up was 2 years. Compared with DDLT recipients, LDLT recipients were more likely to be white (84.5% versus 72.2%) and female (41.1% versus 31.7%), to have lower MELD scores (15 versus 19), and to be classified preoperatively as independent (65.3% versus 46.7%) and not hospitalized (91.3% versus 78.4%). The posttransplant length of stay (LOS), in-hospital mortality, costs, and survival were similar between the groups, but LDLT recipients were more likely to be readmitted within 30 days (44.9% versus 37.1%, P 5 0.001). After matching, the difference in 30-day readmission rates persisted (45.1% versus 33.8%, P 5 0.001), but there were no differences in the LOS, costs, patient survival, or graft survival. This national report shows that LDLT is associated with higher readmission rates in comparison with C 2014 AASLD. DDLT, but the results are comparable for other key patient metrics. Liver Transpl 20:1347-1355, 2014. V Received June 3, 2014; accepted July 4, 2014.
See Editorial on Page 1290
Over the past 10 years, the average annual number of liver transplants performed nationally was just more than 6000, but there are currently more than 15,000
Abbreviations: BMI, body mass index; DDLT, deceased donor liver transplantation; HCC, hepatocellular carcinoma; HV, high-volume tertile; ICU, intensive care unit; IQR, interquartile range; LDLT, living donor liver transplantation; LOS, length of stay; LV, low-volume tertile; MELD, Model for End-Stage Liver Disease; MV, medium-volume tertile; NASH, nonalcoholic steatohepatitis; OLT, orthotopic liver transplantation; Q1, quartile; Q2, quartile 2; Q3, quartile 3; Q4, quartile 4; Q5, quartile 5; SES, socioeconomic status; SRTR, Scientific Registry of Transplant Recipients; TIPS, transjugular intrahepatic portosystemic shunt; UHC, University HealthSystem Consortium. The institutional review board of the University of Cincinnati approved this study, and the Scientific Registry of Transplant Recipients project officer of the Health Resources and Services Administration and the Technical Advisory Committee of the Scientific Registry of Transplant Recipients approved the linkage of the 2 data sets. The data reported here have been supplied by the Minneapolis Medical Research Foundation as the contractor for the Scientific Registry of Transplant Recipients. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy of or interpretation by the Scientific Registry of Transplant Recipients or the US Government. Potential conflict of interest: Nothing to report. This study was supported by the University of Cincinnati Department of Surgery. Address reprint requests to Shimul A. Shah, M.D., M.H.C.M., Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, 231 Albert Sabin Way, ML 0558, MSB 2006C, Cincinnati, OH 45267-0558. Telephone: 513-558-3993; FAX: 513-558-8689; E-mail: [email protected] DOI 10.1002/lt.23956 View this article online at wileyonlinelibrary.com. LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
C 2014 American Association for the Study of Liver Diseases. V
1348 HOEHN ET AL.
people on the waiting list.1 Living donor liver transplantation (LDLT), first performed in the United States in 1989, has been used to augment the donor pool and decrease the wait-list mortality of patients in need of liver transplantation.2 However, many questions have been raised about the safety and efficacy of LDLT. The number of LDLT procedures performed annually in the United States increased rapidly at first but has steadily declined since 2001.1 During this time, there has been increased scrutiny and research regarding the outcomes related to LDLT not only as they pertain to donors but also in comparison with deceased donor liver transplantation (DDLT) in the Western world. The Adult-to-Adult Living Donor Liver Transplantation Cohort studied LDLT from 1998 to 2008 and found that although LDLT recipients had more complications and postoperative hospitalizations, these results improved with increasing center experience with LDLT.3-6 Other studies have shown decreased graft survival with LDLT versus DDLT.7,8 A recent review found that LDLT is safe and in select cases offers advantages over DDLT.9 Much of the literature that has been published about LDLT is from the earlier national experience with LDLT. Our aim was to evaluate the recent LDLT experience on a national level and examine a large number of patients and a representative variety of center experiences. We hypothesized that a patient selection bias may confound reports on outcomes after LDLT, and we attempted to compare medically matched transplant recipients and to evaluate more fairly the safety and cost-effectiveness of LDLT versus DDLT.
PATIENTS AND METHODS Study Population A retrospective cohort study was performed for liver transplants between January 1, 2007, and December 31, 2012. These years were chosen to represent a modern and updated experience and were available for the linkage described later. Data for this study were drawn from 2 different sources. First, clinical data were obtained from the Scientific Registry of Transplant Recipients (SRTR) Standard Analysis File, a national transplant database that provides donor and recipient data collected by the Organ Procurement and Transplantation Network.1 These data were then linked to recipient clinical and hospital encounter data obtained from the University HealthSystem Consortium (UHC) Clinical Database/ Resource Manager. UHC is an alliance of 118 academic medical centers and 298 of their affiliated hospitals and represents approximately 95% of the nation’s major not-for-profit academic medical centers. Theirs is an administrative database containing patient demographic, financial, International Classification of Diseases (Ninth Revision), and procedure data provided by the member medical centers. Hospital charges are reported for each patient encounter
LIVER TRANSPLANTATION, November 2014
and converted to cost estimates with institutionspecific Medicare cost-to-charge ratios and federally reported area wage indices to normalize regional variations in labor costs.10 The direct costs are reported as medians and reflect index transplant admissions only. A linkage of patients in these 2 data sets was performed as previously described11 with recipient age, date of procedure, sex, and transplant center. From January 2007 to December 2012, 34,611 liver transplants from 135 centers were identified from the SRTR database. Over the same time period, 21,868 liver transplants from 67 centers were identified from the UHC database. Recipient age less than 18 years (n 5 1433) and repeat orthotopic liver transplantation (OLT) within the same hospitalization (n 5 396) were excluded from this data set. From these parameters we identified 14,282 DDLT procedures and 715 LDLT procedures performed at 62 and 35 centers, respectively. These represented 43% of the 33,470 DDLT procedures and 63% of the 1141 LDLT procedures performed nationally during the same period. Donor and recipient demographic characteristics of this population were similar to the national transplant cohort. The data were verified to be similar to the SRTR complete data set with regard to donor characteristics as well as recipient cause of liver disease, severity of disease, and survival data. By linking these 2 data sets, we were able to assess transplant-specific outcomes, such as patient and graft survival, as well as hospital-level outcomes, including 30-day readmission, discharge disposition, length of stay (LOS), and cost. The following donor characteristics were collected: age (years), sex, race (white, black, Hispanic, or other), body mass index (BMI), cold ischemia time (hours), and warm ischemia time (minutes). Next, the following recipient characteristics were collected: age (years), sex, race (white, black, Hispanic, or other), BMI, socioeconomic status (SES), insurance type (private, government, or other), cause of liver disease, medical history, functional status (independent, dependent, severely ill), admission status (elective or emergent), physical capacity, severity of illness, pretransplant location [intensive care unit (ICU), ward, not hospitalized], and Model for End-Stage Liver Disease (MELD) score. MELD scores were calculated for each recipient based on the UNOS modification to the formula described as medical MELD scores.12 For the statistical analysis, patients were stratified according to MELD groups similar to those previously used.13
SES A summary measure of SES from U.S. Census American Community Survey 5-year estimates from 2011 for each U.S. zip code was constructed. The individual variables chosen were based on previous methods and included 3 measures of wealth and income (log of median household income; log of median value of housing unit; and percentage of households with interest, dividend, or rental income), 2 measures of
LIVER TRANSPLANTATION, Vol. 20, No. 11, 2014
HOEHN ET AL. 1349
TABLE 1. Comparison of the Liver Allograft Donors for the Linked Cohort of 14,997 Patients Who Underwent DDLT and LDLT From 2007 to 2012 Living Donors Donor Characteristics Overall number of patients Sex Male Female Age of donor (years)
ORIGINAL ARTICLE
Comparing Living Donor and Deceased Donor Liver Transplantation: A Matched National Analysis From 2007 to 2012 Richard S. Hoehn,1 Gregory C. Wilson,1 Koffi Wima,1 Samuel F. Hohmann,2 Emily F. Midura,1 E. Steve Woodle,1 Daniel E. Abbott,1 Ashish Singhal,1 and Shimul A. Shah1 1 Cincinnati Research in Outcomes and Safety in Surgery, Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, OH; and 2University Health System Consortium and Department Health Systems Management, Rush University, Chicago, IL
A complete evaluation of living donor liver transplantation (LDLT) in the United States has been difficult because of the persistent low volume and the lack of adequate comparisons with deceased donor liver transplantation (DDLT). Recent reports have suggested outcomes equivalent to those for DDLT, but these studies did not adjust for differences in recipient selection. From a linkage between the University HealthSystem Consortium and Scientific Registry of Transplant Recipients databases, we identified 14,282 patients at 62 centers who underwent DDLT from 2007 to 2012 and 715 patients at 35 centers who underwent LDLT during the same period. Then, we performed 1:1 propensity score matching for 708 LDLT recipients based on age, Model for End-Stage Liver Disease (MELD) score, and pretransplant patient status. The median follow-up was 2 years. Compared with DDLT recipients, LDLT recipients were more likely to be white (84.5% versus 72.2%) and female (41.1% versus 31.7%), to have lower MELD scores (15 versus 19), and to be classified preoperatively as independent (65.3% versus 46.7%) and not hospitalized (91.3% versus 78.4%). The posttransplant length of stay (LOS), in-hospital mortality, costs, and survival were similar between the groups, but LDLT recipients were more likely to be readmitted within 30 days (44.9% versus 37.1%, P 5 0.001). After matching, the difference in 30-day readmission rates persisted (45.1% versus 33.8%, P 5 0.001), but there were no differences in the LOS, costs, patient survival, or graft survival. This national report shows that LDLT is associated with higher readmission rates in comparison with C 2014 AASLD. DDLT, but the results are comparable for other key patient metrics. Liver Transpl 20:1347-1355, 2014. V Received June 3, 2014; accepted July 4, 2014.
See Editorial on Page 1290
Over the past 10 years, the average annual number of liver transplants performed nationally was just more than 6000, but there are currently more than 15,000
Abbreviations: BMI, body mass index; DDLT, deceased donor liver transplantation; HCC, hepatocellular carcinoma; HV, high-volume tertile; ICU, intensive care unit; IQR, interquartile range; LDLT, living donor liver transplantation; LOS, length of stay; LV, low-volume tertile; MELD, Model for End-Stage Liver Disease; MV, medium-volume tertile; NASH, nonalcoholic steatohepatitis; OLT, orthotopic liver transplantation; Q1, quartile; Q2, quartile 2; Q3, quartile 3; Q4, quartile 4; Q5, quartile 5; SES, socioeconomic status; SRTR, Scientific Registry of Transplant Recipients; TIPS, transjugular intrahepatic portosystemic shunt; UHC, University HealthSystem Consortium. The institutional review board of the University of Cincinnati approved this study, and the Scientific Registry of Transplant Recipients project officer of the Health Resources and Services Administration and the Technical Advisory Committee of the Scientific Registry of Transplant Recipients approved the linkage of the 2 data sets. The data reported here have been supplied by the Minneapolis Medical Research Foundation as the contractor for the Scientific Registry of Transplant Recipients. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy of or interpretation by the Scientific Registry of Transplant Recipients or the US Government. Potential conflict of interest: Nothing to report. This study was supported by the University of Cincinnati Department of Surgery. Address reprint requests to Shimul A. Shah, M.D., M.H.C.M., Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, 231 Albert Sabin Way, ML 0558, MSB 2006C, Cincinnati, OH 45267-0558. Telephone: 513-558-3993; FAX: 513-558-8689; E-mail: [email protected] DOI 10.1002/lt.23956 View this article online at wileyonlinelibrary.com. LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
C 2014 American Association for the Study of Liver Diseases. V
1348 HOEHN ET AL.
people on the waiting list.1 Living donor liver transplantation (LDLT), first performed in the United States in 1989, has been used to augment the donor pool and decrease the wait-list mortality of patients in need of liver transplantation.2 However, many questions have been raised about the safety and efficacy of LDLT. The number of LDLT procedures performed annually in the United States increased rapidly at first but has steadily declined since 2001.1 During this time, there has been increased scrutiny and research regarding the outcomes related to LDLT not only as they pertain to donors but also in comparison with deceased donor liver transplantation (DDLT) in the Western world. The Adult-to-Adult Living Donor Liver Transplantation Cohort studied LDLT from 1998 to 2008 and found that although LDLT recipients had more complications and postoperative hospitalizations, these results improved with increasing center experience with LDLT.3-6 Other studies have shown decreased graft survival with LDLT versus DDLT.7,8 A recent review found that LDLT is safe and in select cases offers advantages over DDLT.9 Much of the literature that has been published about LDLT is from the earlier national experience with LDLT. Our aim was to evaluate the recent LDLT experience on a national level and examine a large number of patients and a representative variety of center experiences. We hypothesized that a patient selection bias may confound reports on outcomes after LDLT, and we attempted to compare medically matched transplant recipients and to evaluate more fairly the safety and cost-effectiveness of LDLT versus DDLT.
PATIENTS AND METHODS Study Population A retrospective cohort study was performed for liver transplants between January 1, 2007, and December 31, 2012. These years were chosen to represent a modern and updated experience and were available for the linkage described later. Data for this study were drawn from 2 different sources. First, clinical data were obtained from the Scientific Registry of Transplant Recipients (SRTR) Standard Analysis File, a national transplant database that provides donor and recipient data collected by the Organ Procurement and Transplantation Network.1 These data were then linked to recipient clinical and hospital encounter data obtained from the University HealthSystem Consortium (UHC) Clinical Database/ Resource Manager. UHC is an alliance of 118 academic medical centers and 298 of their affiliated hospitals and represents approximately 95% of the nation’s major not-for-profit academic medical centers. Theirs is an administrative database containing patient demographic, financial, International Classification of Diseases (Ninth Revision), and procedure data provided by the member medical centers. Hospital charges are reported for each patient encounter
LIVER TRANSPLANTATION, November 2014
and converted to cost estimates with institutionspecific Medicare cost-to-charge ratios and federally reported area wage indices to normalize regional variations in labor costs.10 The direct costs are reported as medians and reflect index transplant admissions only. A linkage of patients in these 2 data sets was performed as previously described11 with recipient age, date of procedure, sex, and transplant center. From January 2007 to December 2012, 34,611 liver transplants from 135 centers were identified from the SRTR database. Over the same time period, 21,868 liver transplants from 67 centers were identified from the UHC database. Recipient age less than 18 years (n 5 1433) and repeat orthotopic liver transplantation (OLT) within the same hospitalization (n 5 396) were excluded from this data set. From these parameters we identified 14,282 DDLT procedures and 715 LDLT procedures performed at 62 and 35 centers, respectively. These represented 43% of the 33,470 DDLT procedures and 63% of the 1141 LDLT procedures performed nationally during the same period. Donor and recipient demographic characteristics of this population were similar to the national transplant cohort. The data were verified to be similar to the SRTR complete data set with regard to donor characteristics as well as recipient cause of liver disease, severity of disease, and survival data. By linking these 2 data sets, we were able to assess transplant-specific outcomes, such as patient and graft survival, as well as hospital-level outcomes, including 30-day readmission, discharge disposition, length of stay (LOS), and cost. The following donor characteristics were collected: age (years), sex, race (white, black, Hispanic, or other), body mass index (BMI), cold ischemia time (hours), and warm ischemia time (minutes). Next, the following recipient characteristics were collected: age (years), sex, race (white, black, Hispanic, or other), BMI, socioeconomic status (SES), insurance type (private, government, or other), cause of liver disease, medical history, functional status (independent, dependent, severely ill), admission status (elective or emergent), physical capacity, severity of illness, pretransplant location [intensive care unit (ICU), ward, not hospitalized], and Model for End-Stage Liver Disease (MELD) score. MELD scores were calculated for each recipient based on the UNOS modification to the formula described as medical MELD scores.12 For the statistical analysis, patients were stratified according to MELD groups similar to those previously used.13
SES A summary measure of SES from U.S. Census American Community Survey 5-year estimates from 2011 for each U.S. zip code was constructed. The individual variables chosen were based on previous methods and included 3 measures of wealth and income (log of median household income; log of median value of housing unit; and percentage of households with interest, dividend, or rental income), 2 measures of
LIVER TRANSPLANTATION, Vol. 20, No. 11, 2014
HOEHN ET AL. 1349
TABLE 1. Comparison of the Liver Allograft Donors for the Linked Cohort of 14,997 Patients Who Underwent DDLT and LDLT From 2007 to 2012 Living Donors Donor Characteristics Overall number of patients Sex Male Female Age of donor (years)
