Outcomes of Liver Transplantation With Liver ... - Wiley Online Library

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Justin H. Nguyen, and C. Burcin Taner for Mayo Clinic Collaborative in Transplant ...... 22) Gu L, Fang H, Li F, Zhang S, Shen C, Han L. Impact of hepat-.
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CROOME ET AL.

Outcomes of Liver Transplantation With Liver Grafts From Pediatric Donors Used in Adult Recipients Kristopher P. Croome, David D. Lee, Justin M. Burns, Hector Saucedo-Crespo, Dana K. Perry, Justin H. Nguyen, and C. Burcin Taner for Mayo Clinic Collaborative in Transplant Research and Outcomes Department of Transplant, Mayo Clinic Florida, Jacksonville, FL Although there is an agreement that liver grafts from pediatric donors (PDs) should ideally be used for pediatric patients, there remain situations when these grafts are turned down for pediatric recipients and are then offered to adult recipients. The present study aimed to investigate the outcomes of using these grafts for liver transplantation (LT) in adult patients. Data from all patients undergoing LT between 2002 and 2014 were obtained from the United Network for Organ Sharing Standard Analysis and Research file. Adult recipients undergoing LT were divided into 2 groups: those receiving a pediatric liver graft (pediatric-to-adult group) and those receiving a liver graft from adult donors (adult-to-adult group). A separate subgroup analysis comparing the PDs used for adult recipients and those used for pediatric recipients was also performed. Patient and graft survival were not significantly different between pediatric-to-adult and adult-to-adult groups (P 5 0.08 and P 5 0.21, respectively). Hepatic artery thrombosis as the cause for graft loss was higher in the pediatric-to-adult group (3.6%) than the adult-to-adult group (1.9%; P < 0.001). A subanalysis looking at the pediatric-to-adult group found that patients with a predicted graft-torecipient weight ratio (GRWR) < 0.8 had a higher 90-day graft loss rate than those with a GRWR  0.8 (39% versus 9%; P < 0.001). PDs used for adult recipients had a higher proportion of donors with elevated aspartate aminotransferase/alanine aminotransferase (20% vs. 12%; P < 0.001), elevated creatinine (11% vs. 4%; P < 0.001), donation after cardiac death donors (12% vs. 0.9%; P < 0.001), and were hepatitis B virus core positive (1% vs. 0.3%; P 5 0.002) than PDs used for pediatric recipients. In conclusion, acceptable patient and graft survival can be achieved with the use of pediatric liver grafts in adult recipients, when these grafts have been determined to be inappropriate for usage in the pediatric population.

Liver Transplantation 22 1099-1106 2016 AASLD. Received December 20, 2015; accepted March 29, 2016.

SEE EDITORIAL ON PAGE 1065 In the transplant community, there has been a general consensus that pediatric donor (PD) livers should ideally be used for pediatric recipients. In order to facilitate

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BSA, body surface area; CDC, Centers for Disease Control and Prevention; CIT, cold ischemia time; Cr, creatinine; DCD, donation after cardiac death; DRI, donor risk index; GRWR, graft-to-recipient weight ratio; HAT, hepatic artery thrombosis; HBc, hepatitis B virus core positive; HCC, hepatocellular carcinoma; HR, hazard ratio; LDLT, living donor liver transplantation; LT, liver transplantation; MELD, Model for End-Stage Liver Disease; NA, not available; NASH, nonalcoholic steatohepatitis; OR, odds ratio; PD, pediatric donor; sTLV, standardized total liver volume; TLV, total liver volume; UNOS, United Network for Organ Sharing.

their use in the pediatric population, changes in organ allocation were implemented in 2005 so that pediatric liver grafts are regionally shared.(1) Although there is an agreement that this represents the optimal allocation of these organs for the benefit of pediatric recipients, there remain situations when these liver grafts are turned down for the pediatric recipient pool and they are subsequently offered to adult recipients. To help address the rising discrepancy between the number of potential liver transplantation (LT) candidates and the availability of liver grafts, it is important that the transplant community continues to pursue maximal use of any potential organ offer.(2) One of the major concerns in using liver grafts from PDs in adults is inadequate liver graft volume. The negative impact of “small-for-size” grafts has been well described in the field of living donor liver transplantation (LDLT) and with the use of split-liver grafts.(3) In LDLT, it is now generally accepted that grafts must be greater than 0.8% of recipient body

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weight.(4) Liver grafts from PDs have also been shown to be associated with a higher risk of hepatic artery thrombosis (HAT) in the pediatric LT literature, leading to concerns in using these organs for adult patients especially in the era of increased scrutiny of short-term and longterm outcomes.(5,6) There is a paucity of published analyses on the utilization of liver grafts from PDs in adult recipients.(7-9) It is important that the results of these grafts in adult recipients be known. The present study aimed to investigate the outcomes of using pediatric liver grafts in adult patients using a large US national database. Secondary goals were to examine the changes in trends of use over time and to compare outcomes of these grafts used for pediatric recipients to those used for adult recipients.

Patients and Methods Data were obtained and extracted from the United Network for Organ Sharing (UNOS) Standard Analysis and Research file. The study population included all deceased donor LT recipients in the United States from February 27, 2002 to November 30, 2014. Data abstracted from the UNOS database included all relevant donor and recipient factors. PDs were defined as

Address reprint requests to C. Burcin Taner, M.D., Department of Transplant, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL 32224. Telephone: 904-956-3261; E-mail: [email protected] Funding provided internally by Mayo Clinic Collaborative in Transplant Research and Outcomes. Kristopher P. Croome, Justin M. Burns, David D. Lee, Dana K. Perry, Justin H. Nguyen, and C. Burcin Taner participated in research design. Kristopher P. Croome, David D. Lee, and C. Burcin Taner participated in data analysis. Kristopher P. Croome, David D. Lee, and Hector Saucedo-Crespo participated in the performance of the research. Kristopher P. Croome, David D. Lee, and C. Burcin Taner participated in the writing of the article. Kristopher P. Croome and C. Burcin Taner gave final approval. Additional supporting information may be found in the online version of this article. C 2016 by the American Association for the Study of Liver Copyright V Diseases.

View this article online at wileyonlinelibrary.com. DOI 10.1002/lt.24466 Potential conflict of interest: Nothing to report.

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donors  12 years of age based on previous studies.(7) Adult donors as well as adult recipients were defined as  18 years of age. Adult recipients undergoing LT were divided into 2 groups: those receiving a PD liver graft (pediatric-to-adult) and those receiving an adult donor liver graft (adult-to-adult). Standardized total liver volume (sTLV) for all adult recipients and donors were calculated using the previously published and validated formula: –794.41 1 1267.28 3 body surface area (BSA; m(2).(10-12) The Mosteller formula (BSA 5 冑[weight 3 height/6] was used to calculate recipient BSA.(13) A formula validated for pediatric patients was used to calculate sTLV for all pediatric recipients and donors (sTLV 5 689.9 3 BSA – 24.7).(14) For this formula, BSA was calculated by the DuBois formula (BSA 5 body weight0.425 3 height0.725 3 0.007184).(15) Graft-to-recipient weight ratio (GRWR) was calculated by graft liver weight (donor sTLV)/recipient weight. A GRWR of  0.8 was used as a cutoff based on previous studies.(3) Graft survival was calculated from the time of LT until death, graft loss, or date of last follow-up. The occurrence and the date of death were obtained from data reported to the Scientific Registry of Transplant Recipients by the transplant centers and were completed by data from the US Social Security Administration and from the OPTN. Potentially confounding donor and recipient factors were examined including the donor risk index (DRI), recipient age, Model for EndStage Liver Disease (MELD) score at transplant, body mass index (BMI), sex, race, retransplant status, etiology of liver disease, and presence of hepatocellular carcinoma (HCC) as secondary diagnosis. A separate subgroup analysis was performed comparing the pediatric-to-adult group (PDs  12 years of age and adult recipients) and PDs that had been used for pediatric recipients in order to investigate reasons why the organs used for the adult recipients had been turned down for the pediatric population. Because the allocation of pediatric livers has only been preferentially allocated regionally to pediatric recipients since 2005, data prior to 2005 were excluded from this portion of the analysis. Refusal codes for all organs were reviewed. Data were weighted so that each donor was only counted once, not once per individual recipient refusal. This was done so that a donor with 500 refusals contributed the same as a donor with only 1 refusal. All statistical analyses were performed using STATA, version 12 (Stata Corp., College Station, TX). Differences between groups were analyzed using the unpaired t test for continuous variables and by the

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TABLE 1. Recipient Characteristics in Pediatric-to-Adult and Adult-to-Adult Groups Recipient Characteristics Age at transplant, years Body mass index Sex, male Diagnosis Hepatitis C virus serology EtOH NASH Cholestatic HCC exception Calculated MELD score Match MELD score Retransplant Days on waiting list (at transplanting center) Race/ethnicity White Black Other Recipient sTLV, cc

Pediatric-to-Adult Group (n 5 968)

Adult-to-Adult Group (n 5 66,996)

P Value

50.8 6 13.1 24.7 6 5.3 343 (35)

53.6 6 10.3 28.2 6 5.7 45,426 (68)