© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Clin Transplant 2015: 29: 60–66 DOI: 10.1111/ctr.12484
Clinical Transplantation
Outcomes after combined liver–kidney transplant vs. kidney transplant followed by liver transplant Chan EY, Bhattacharya R, Eswaran S, Hertl M, Shah N, Fayek S, Cohen EB, Hollinger EF, Olaitan O, Jensik SC, Perkins JD. Outcomes after combined liver–kidney transplant vs. kidney transplant followed by liver transplant. Abstract: Introduction: The decision for isolated kidney transplant (KT) vs. combined liver–kidney transplant (CLKT) in patients with end-stage renal disease (ESRD) with compensated cirrhosis remains controversial. We sought to determine outcomes of patients requiring listing for a liver transplant (LT) following either a cadaveric or living donor KT and compare these outcomes to similar patients receiving a CLKT. Methods: Our dataset included the United Network for Organ Sharing (UNOS)/Standard Transplant and Analysis and Research (STAR) kidney files from 1987 to 2012 after being joined with the liver files from 2002 to 2012. Outcomes of patients who received a CLKT with an international normalized ratio (INR) ≤1 and total bilirubin ≤1 were compared to patients who received a primary KT and subsequently required listing for LT between zero and five yr or after five yr. Results: For the three groups, 244 patients had a CLKT, 216 were waitlisted for LT between zero and five yr after KT (0–5 WL), and 320 were wait-listed five yr after KT (+5 WL). From the time of KT, the 0–5 WL group had significantly worse survival than the CLKT group and the +5 WL group. The +5 WL had the best survival of all groups. For the 0–5 WL group, 45% underwent LT and 40% died while waiting compared to the +5 WL group with 53% having LT and 26% died while waiting. At the time of LT, the 0–5 WL group had a higher model for end-stage liver disease (MELD) score, higher incidence of being in the ICU at the time of transplant, and higher incidence of requiring life support. From the time of LT, the CLKT trended toward better survival (p = 0.0549) than both the 0–5 WL and +5 WL groups, which had equivalent survival. Conclusion: The 0–5 WL group is a higher risk group with poorer survival due to a higher incidence of dying on the waitlist. Better identification of patients with a high risk for hepatic decompensation following KT and agreement for regional exception for LT in the event of decompensation may improve utilization of organs and better survival for those patients.
The decision for isolated kidney transplant (KT) vs. combined liver–kidney transplant (CLKT) in patients with end-stage renal disease (ESRD) with compensated cirrhosis remains controversial. With the adoption of the model for end-stage liver disease (MELD) score in 2002 for cadaveric liver allocation, the numbers of CLKT have increased by 300% (1). There are currently no standard national or regional policies regarding requirements for listing for CLKT. The decision to list a patient for CLKT is determined by an individual transplant
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Edie Y. Chana, Renuka Bhattacharyab, Sheila Eswaranc, Martin Hertla, Nikunj Shahc, Sameh Fayeka, Eric B. Cohenc, Edward F. Hollingera, Oyedolamu Olaitana, Stephen C. Jensika and James D. Perkinsd a
Department of General Surgery, Rush University Medical Center, Chicago, IL, b Department of Medicine, University of Washington Medical Center, Seattle, WA, c Department of Medicine, Rush University Medical Center, Chicago, IL and dDepartment of Surgery, University of Washington Medical Center, Seattle, WA, USA
Key words: cirrhosis – combined liver–kidney transplant – kidney transplant – liver transplant – outcomes Corresponding author: Edie Y. Chan, MD, Section of Abdominal Transplant/Department of General Surgery, Rush University Medical Center, 1653 W. Congress Pkwy, Chicago, IL 60612, USA. Tel.: +1 312 942 3074; fax: +1 312 942 2509; e-mail: [email protected] Conflict of interest: None. Accepted for publication 30 October 2014
program and is not subject to regulatory compliance. Several reasons may play into the decision-making for performing a CLKT instead of a KT, followed by a LT, if needed. For patients with known cirrhosis undergoing a non-LT operation, the mortality of a Child’s A cirrhotic remains approximately 10% (2, 3). In patients with a MELD score >15, the mortality is 17–50% (4). This MELD score is below the calculated MELD score of 20 for patients with ESRD on hemodialysis and
Outcomes of CLKT vs. KT followed by LT compensated cirrhosis (total bilirubin ≤1, international normalized ratio [INR] ≤1). In contrast, the current national one-yr survival for kidney transplantation (based on 34 171 transplants) is 97% (5). With increased scrutiny of transplant centerspecific outcomes, the increased risk of death for patients with cirrhosis receiving a KT and developing hepatic decompensation would be prohibitive. Currently, there are no prospective randomized trials comparing KT alone vs. CLKT in patients with ESRD on hemodialysis (HD) and asymptomatic cirrhosis. There are also very few data on outcomes in this subgroup of patients. One recently published series reviewed outcomes in patients with hepatitis C undergoing KT. Compared to their hepatitis C negative counterparts, these patients had overall worse survival. Both univariate and multivariate analysis identified hepatic fibrosis or cirrhosis was a predictor of worse outcomes (6). While the numbers of patients were few in this series, this may also lead to bias toward CLKT. As the data remain poorly studied, we sought to determine outcomes of patients who required listing for LT after cadaveric or living donor KT using the United Network for Organ Sharing (UNOS)/Standard Transplant and Analysis and Research (STAR) files. We then compared the KT patient survival to patient survival undergoing CLKT with similar liver disease status. Methods
Our dataset included the UNOS/STAR files on KTs from 1987 to 2012, which was then joined by a unique identifier with the liver files from 2002 to 2012. Files were based on data as of June 7, 2013. Patients who were listed for a CLKT with a total bilirubin ≤1 and an INR ≤1 were compared to patients who received a primary KT and subsequently required listing for LT between zero and five yr or after five yr. At the time of listing for KT, recipient factors collected included hepatitis B virus core antibody serology (HBV core AB), hepatitis B virus surface antibody serology (HBV surface Ab), hepatitis C antibody serology (HCV), location at the time of KT, deceased or living donor kidney, gender, and age. At the time of listing for LT, recipient factors collected included the presence of transjugular intrahepatic portosystemic shunt (TIPSS), hepatic encephalopathy (grade 2 or greater), portal hypertension, ascites (moderate or greater), INR, total bilirubin, model for end-stage liver disease (MELD) score, the presence of hepatocellular carcinoma (HCC), and requiring assistance for living. Other factors collected at the time
of LT included location at the time of transplant, on life support, age, and MELD score. Statistical analysis
Continuous variables were expressed as the mean standard deviation (SD), and categorical variables were presented as percentages. With normal distributions, the Student’s t-test was used for testing continuous variables, and the chi-square test was used for categorical variables. Survival analysis with log-rank test was evaluated using JMP Pro 11.1.1 statistical software package (SAS Institute, Cary, NC, USA). A p-value ≤0.05 was considered significant. Results
From the time of listing for KT, patients listed for CLKT had a higher incidence of having a positive serology for HBV core Ab, HBV surface Ab, and HCV antibody. However, serologies were often not recorded in the WL +5 group (Table 1). The CLKT group also had a higher incidence of HCC (14%) compared to the other two groups. Patients listed for CLKT had a much higher incidence of HCV positivity than patients who were listed for KT at any other time (Table 2). Liver data including INR, encephalopathy, bilirubin, and MELD score are not collected at the time of listing for KT. In comparing the three groups at the time of listing for LT, the 0–5 WL group had more encephalopathy, higher INR, higher total bilirubin, and higher MELD score and required more assistance to live (Table 3). At the time of LT, the 0–5 WL group had a higher MELD score and was more likely to be located in the ICU at the time of transplant and require life support (Table 4). For the three groups, 244 patients received a CLKT, 216 patients were wait-listed for an LT between zero and five yr after KT (0–5 WL), and 320 patients were wait-listed five yr after KT (+5 WL). Comparing outcomes from the time of KT, the 0–5 WL group had significantly worse survival than the CLKT and the +5 WL group. The +5 WL group had the best survival of all the groups (Fig. 1). Within this group, patients who required listing within one yr had the worst one-yr survival, followed by the CLKT group. Patients who required listing within 2–3 yr had a marked decrease in survival after two yr. For the 0–5 WL group, 45% underwent LT and 40% died while waiting (Fig. 2). For the +5 WL group, 53% received a LT and 26% died while waiting. Patients requiring listing for LT >6 yr after KT had the best survival.
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Chan et al. Table 1. Recipient factors at the time of kidney listing Combined liver–kidney transplant Total transplanted and wait listed Male HBV Core Ab Negative Positive Unknown HBV Surface Ab Negative Positive Unknown HCV antibody Negative Positive Unknown Location at time of KT ICU In hospital Home Living donor KT
p-value
244 148 (60.7%)
216 138 (63.9%)
320 223 (69.7%)
169 (69.3%) 49 (20.1%) 26 (10.7%)
131 (60.7%) 36 (16.7%) 49 (22.7%)
132 (41.3%) 25 (7.8%) 163 (50.9%)
Clin Transplant 2015: 29: 60–66 DOI: 10.1111/ctr.12484
Clinical Transplantation
Outcomes after combined liver–kidney transplant vs. kidney transplant followed by liver transplant Chan EY, Bhattacharya R, Eswaran S, Hertl M, Shah N, Fayek S, Cohen EB, Hollinger EF, Olaitan O, Jensik SC, Perkins JD. Outcomes after combined liver–kidney transplant vs. kidney transplant followed by liver transplant. Abstract: Introduction: The decision for isolated kidney transplant (KT) vs. combined liver–kidney transplant (CLKT) in patients with end-stage renal disease (ESRD) with compensated cirrhosis remains controversial. We sought to determine outcomes of patients requiring listing for a liver transplant (LT) following either a cadaveric or living donor KT and compare these outcomes to similar patients receiving a CLKT. Methods: Our dataset included the United Network for Organ Sharing (UNOS)/Standard Transplant and Analysis and Research (STAR) kidney files from 1987 to 2012 after being joined with the liver files from 2002 to 2012. Outcomes of patients who received a CLKT with an international normalized ratio (INR) ≤1 and total bilirubin ≤1 were compared to patients who received a primary KT and subsequently required listing for LT between zero and five yr or after five yr. Results: For the three groups, 244 patients had a CLKT, 216 were waitlisted for LT between zero and five yr after KT (0–5 WL), and 320 were wait-listed five yr after KT (+5 WL). From the time of KT, the 0–5 WL group had significantly worse survival than the CLKT group and the +5 WL group. The +5 WL had the best survival of all groups. For the 0–5 WL group, 45% underwent LT and 40% died while waiting compared to the +5 WL group with 53% having LT and 26% died while waiting. At the time of LT, the 0–5 WL group had a higher model for end-stage liver disease (MELD) score, higher incidence of being in the ICU at the time of transplant, and higher incidence of requiring life support. From the time of LT, the CLKT trended toward better survival (p = 0.0549) than both the 0–5 WL and +5 WL groups, which had equivalent survival. Conclusion: The 0–5 WL group is a higher risk group with poorer survival due to a higher incidence of dying on the waitlist. Better identification of patients with a high risk for hepatic decompensation following KT and agreement for regional exception for LT in the event of decompensation may improve utilization of organs and better survival for those patients.
The decision for isolated kidney transplant (KT) vs. combined liver–kidney transplant (CLKT) in patients with end-stage renal disease (ESRD) with compensated cirrhosis remains controversial. With the adoption of the model for end-stage liver disease (MELD) score in 2002 for cadaveric liver allocation, the numbers of CLKT have increased by 300% (1). There are currently no standard national or regional policies regarding requirements for listing for CLKT. The decision to list a patient for CLKT is determined by an individual transplant
60
Edie Y. Chana, Renuka Bhattacharyab, Sheila Eswaranc, Martin Hertla, Nikunj Shahc, Sameh Fayeka, Eric B. Cohenc, Edward F. Hollingera, Oyedolamu Olaitana, Stephen C. Jensika and James D. Perkinsd a
Department of General Surgery, Rush University Medical Center, Chicago, IL, b Department of Medicine, University of Washington Medical Center, Seattle, WA, c Department of Medicine, Rush University Medical Center, Chicago, IL and dDepartment of Surgery, University of Washington Medical Center, Seattle, WA, USA
Key words: cirrhosis – combined liver–kidney transplant – kidney transplant – liver transplant – outcomes Corresponding author: Edie Y. Chan, MD, Section of Abdominal Transplant/Department of General Surgery, Rush University Medical Center, 1653 W. Congress Pkwy, Chicago, IL 60612, USA. Tel.: +1 312 942 3074; fax: +1 312 942 2509; e-mail: [email protected] Conflict of interest: None. Accepted for publication 30 October 2014
program and is not subject to regulatory compliance. Several reasons may play into the decision-making for performing a CLKT instead of a KT, followed by a LT, if needed. For patients with known cirrhosis undergoing a non-LT operation, the mortality of a Child’s A cirrhotic remains approximately 10% (2, 3). In patients with a MELD score >15, the mortality is 17–50% (4). This MELD score is below the calculated MELD score of 20 for patients with ESRD on hemodialysis and
Outcomes of CLKT vs. KT followed by LT compensated cirrhosis (total bilirubin ≤1, international normalized ratio [INR] ≤1). In contrast, the current national one-yr survival for kidney transplantation (based on 34 171 transplants) is 97% (5). With increased scrutiny of transplant centerspecific outcomes, the increased risk of death for patients with cirrhosis receiving a KT and developing hepatic decompensation would be prohibitive. Currently, there are no prospective randomized trials comparing KT alone vs. CLKT in patients with ESRD on hemodialysis (HD) and asymptomatic cirrhosis. There are also very few data on outcomes in this subgroup of patients. One recently published series reviewed outcomes in patients with hepatitis C undergoing KT. Compared to their hepatitis C negative counterparts, these patients had overall worse survival. Both univariate and multivariate analysis identified hepatic fibrosis or cirrhosis was a predictor of worse outcomes (6). While the numbers of patients were few in this series, this may also lead to bias toward CLKT. As the data remain poorly studied, we sought to determine outcomes of patients who required listing for LT after cadaveric or living donor KT using the United Network for Organ Sharing (UNOS)/Standard Transplant and Analysis and Research (STAR) files. We then compared the KT patient survival to patient survival undergoing CLKT with similar liver disease status. Methods
Our dataset included the UNOS/STAR files on KTs from 1987 to 2012, which was then joined by a unique identifier with the liver files from 2002 to 2012. Files were based on data as of June 7, 2013. Patients who were listed for a CLKT with a total bilirubin ≤1 and an INR ≤1 were compared to patients who received a primary KT and subsequently required listing for LT between zero and five yr or after five yr. At the time of listing for KT, recipient factors collected included hepatitis B virus core antibody serology (HBV core AB), hepatitis B virus surface antibody serology (HBV surface Ab), hepatitis C antibody serology (HCV), location at the time of KT, deceased or living donor kidney, gender, and age. At the time of listing for LT, recipient factors collected included the presence of transjugular intrahepatic portosystemic shunt (TIPSS), hepatic encephalopathy (grade 2 or greater), portal hypertension, ascites (moderate or greater), INR, total bilirubin, model for end-stage liver disease (MELD) score, the presence of hepatocellular carcinoma (HCC), and requiring assistance for living. Other factors collected at the time
of LT included location at the time of transplant, on life support, age, and MELD score. Statistical analysis
Continuous variables were expressed as the mean standard deviation (SD), and categorical variables were presented as percentages. With normal distributions, the Student’s t-test was used for testing continuous variables, and the chi-square test was used for categorical variables. Survival analysis with log-rank test was evaluated using JMP Pro 11.1.1 statistical software package (SAS Institute, Cary, NC, USA). A p-value ≤0.05 was considered significant. Results
From the time of listing for KT, patients listed for CLKT had a higher incidence of having a positive serology for HBV core Ab, HBV surface Ab, and HCV antibody. However, serologies were often not recorded in the WL +5 group (Table 1). The CLKT group also had a higher incidence of HCC (14%) compared to the other two groups. Patients listed for CLKT had a much higher incidence of HCV positivity than patients who were listed for KT at any other time (Table 2). Liver data including INR, encephalopathy, bilirubin, and MELD score are not collected at the time of listing for KT. In comparing the three groups at the time of listing for LT, the 0–5 WL group had more encephalopathy, higher INR, higher total bilirubin, and higher MELD score and required more assistance to live (Table 3). At the time of LT, the 0–5 WL group had a higher MELD score and was more likely to be located in the ICU at the time of transplant and require life support (Table 4). For the three groups, 244 patients received a CLKT, 216 patients were wait-listed for an LT between zero and five yr after KT (0–5 WL), and 320 patients were wait-listed five yr after KT (+5 WL). Comparing outcomes from the time of KT, the 0–5 WL group had significantly worse survival than the CLKT and the +5 WL group. The +5 WL group had the best survival of all the groups (Fig. 1). Within this group, patients who required listing within one yr had the worst one-yr survival, followed by the CLKT group. Patients who required listing within 2–3 yr had a marked decrease in survival after two yr. For the 0–5 WL group, 45% underwent LT and 40% died while waiting (Fig. 2). For the +5 WL group, 53% received a LT and 26% died while waiting. Patients requiring listing for LT >6 yr after KT had the best survival.
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Chan et al. Table 1. Recipient factors at the time of kidney listing Combined liver–kidney transplant Total transplanted and wait listed Male HBV Core Ab Negative Positive Unknown HBV Surface Ab Negative Positive Unknown HCV antibody Negative Positive Unknown Location at time of KT ICU In hospital Home Living donor KT
p-value
244 148 (60.7%)
216 138 (63.9%)
320 223 (69.7%)
169 (69.3%) 49 (20.1%) 26 (10.7%)
131 (60.7%) 36 (16.7%) 49 (22.7%)
132 (41.3%) 25 (7.8%) 163 (50.9%)
