The shortage of available cadaver organs has prompted the transplant community to consider living donor liver transplantation (LDLT) as an effective alternative to cadaveric liver transplantation (CLT). The potential limitations of LDLT consist primarily of 1) the potential risk to an otherwise healthy donor, and 2) the uncertainty regarding graft and patient outcomes for LDLT as compared to CLT. The core project of this proposal will compare outcomes for recipients of LDLT to those of CLT, while addressing the potential complications to living donors. In addition, we propose to analyze two separate issues. First, we will evaluate donor hepatic steatosis in both LDLT and CLT. We will compare novel non-invasive measurements of steatosis in living donors with the current gold standard, a liver biopsy. We will compare the results of transplanting steatotic livers from living and cadaveric donors, assessing graft and patient outcomes in both groups. We will also evaluate the role of hepatic steatosis on liver regeneration in both the living donor and recipient. We hypothesize that outcome of transplantation in steatotic livers of LDLT is superior to results obtained in steatotic CLT recipients.
This first aim will help design a decision algorithm for the use of steatotic livers in both CLT and LDLT while validating non-invasive measurements of hepatic steatosis. Second, we propose to address the potential role for LDLT in the multimodal management of hepatocellular carcinoma (HCC). Given the lack of randomized trials and large case series, this issue has been recently addressed in studies utilizing decision-modeling analysis.
This second aim will provide clinical data to validate these studies, and will compare CLT, with its inherent waiting times, to LDLT, a strategy that theoretically eliminates waiting times. We hypothesize that the outcome of transplantation of HCC in LDLT is superior to results obtained with CLT. In the aggregate, these studies will define the efficacy of LDLT in the US, while a focus on both a donor issue (hepatic steatosis) and a recipient issue (the special problem of HCC) will help delineate the potential advantages of LDLT over CLT.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZDK1-GRB-D (M1))
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Everhart, James
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Northwestern University at Chicago
Schools of Medicine
United States
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Dew, Mary Amanda; Butt, Zeeshan; Liu, Qian et al. (2018) Prevalence and Predictors of Patient-Reported Long-term Mental and Physical Health After Donation in the Adult-to-Adult Living-Donor Liver Transplantation Cohort Study. Transplantation 102:105-118
Butt, Zeeshan; DiMartini, Andrea F; Liu, Qian et al. (2018) Fatigue, Pain, and Other Physical Symptoms of Living Liver Donors in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study. Liver Transpl 24:1221-1232
Butt, Z; Dew, M A; Liu, Q et al. (2017) Psychological Outcomes of Living Liver Donors From a Multicenter Prospective Study: Results From the Adult-to-Adult Living Donor Liver Transplantation Cohort Study2 (A2ALL-2). Am J Transplant 17:1267-1277
Levitsky, Josh; Goldberg, David; Smith, Abigail R et al. (2017) Acute Rejection Increases Risk of Graft Failure and Death in Recent Liver Transplant Recipients. Clin Gastroenterol Hepatol 15:584-593.e2
DiMartini, A; Dew, M A; Liu, Q et al. (2017) Social and Financial Outcomes of Living Liver Donation: A Prospective Investigation Within the Adult-to-Adult Living Donor Liver Transplantation Cohort Study 2 (A2ALL-2). Am J Transplant 17:1081-1096
Baker, Talia B; Zimmerman, Michael A; Goodrich, Nathan P et al. (2017) Biliary reconstructive techniques and associated anatomic variants in adult living donor liver transplantations: The adult-to-adult living donor liver transplantation cohort study experience. Liver Transpl 23:1519-1530
Dew, M A; Butt, Z; Humar, A et al. (2017) Long-Term Medical and Psychosocial Outcomes in Living Liver Donors. Am J Transplant 17:880-892
Emond, Jean C; Goodrich, Nathan P; Pomposelli, James J et al. (2017) Hepatic Hemodynamics and Portal Flow Modulation: The A2ALL Experience. Transplantation 101:2375-2384
Mandell, M Susan; Smith, Abigail R; Dew, Mary Amanda et al. (2016) Early Postoperative Pain and its Predictors in the Adult to Adult Living Donor Liver Transplantation Cohort Study. Transplantation 100:2362-2371
Dew, Mary Amanda; DiMartini, Andrea F; Ladner, Daniela P et al. (2016) Psychosocial Outcomes 3 to 10 Years After Donation in the Adult to Adult Living Donor Liver Transplantation Cohort Study. Transplantation 100:1257-69

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