Our understanding of ALDLT has advanced significantly since the initial establishment of the A2ALL consortium;however, several important research issues and clinical questions regarding ALDLT remain unanswered. These include fundamental questions regarding the impact of this procedure on the long-term health and well-being of living donors, especially beyond the 1st year postdonation. With regards to recipient outcomes, the technical surgical problems associated with the procedure remain of paramount importance and the surgical limitations of this procedure, as well as methods to overcome these problems, are poorly defined. Our overall goals are to study the short- and long-term effects of ALDLT on the donor and recipient and to gain insight into unique donor and recipient issues through study of this innovative procedure, which will be achieved by full participation in the A2ALL consortium in collaboration with other transplant centers and the data coordinating center. With regards to long- term donor follow up, our aim is to advance beyond generic measures of QOL already included in A2ALL and determine (a) the prevalence and temporal patterns of psychiatric symptomatology and diagnosable mood and anxiety disorders in the extended years following donation;(b) the level of enduring fatigue, other somatic symptoms, and lasting health concerns in the extended years post-donation;and (c) identify the long term financial consequences for donors including health-related financial expenses, changes in employment, and changes in health, disability, or life insurance benefits. Finally, with regards to specific technical issues related to the recipient surgery, our aim is to study the specific risk factors involved in the development of small-for-size-syndrome (SFSS) in recipients after ALDLT - most specifically the impact of portal pressure measurements and inflow modification on the risk for SFSS. Our hypothesisis is that SFSS likely represents a portal hyperperfusion injury to the hepatic sinusoids and measurements of portal pressures and portal flow likely represents the best predictor for SFSS. A randomized study is proposed to look at the impact of inflow modification (specifically splenic artery ligation) vs. no intervention on liver regeneration and risk for developing SFSS in recipients identified to have elevated portal pressure post reperfusion of the liver graft.

Public Health Relevance

A collaborative effort such as the A2ALL will be the only way to advance the field of adult living donor liver transplant in this country as there are no single centers doing enough volume of this procedure to perform any meaningful analysis. The findings from this effort will help to better define the role of this procedure in this country today, the risks (especially long term for the donor) associated with donation, and methods that can perhaps improve the success rates seen with this procedure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK085587-05
Application #
8542823
Study Section
Special Emphasis Panel (ZDK1-GRB-8 (O2))
Program Officer
Sherker, Averell H
Project Start
2009-09-30
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2013
Total Cost
$247,022
Indirect Cost
$107,022
Name
University of Pittsburgh
Department
Surgery
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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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