Our project addresses key issues in adult-to-adult living donor liver transplantation (LDLT). The Main Trial is an extension of the ongoing A2ALL Study - our program is an active participant and the leading enroller of patients to this trial. The current application indicates that we intend to continue to participate, accrue, and enroll patients to the trial. In the Main Trial, we will compare outcomes of LDLT recipients to the outcomes of contemporaneously studied patients undergoing deceased donor liver transplantation (DDLT). Also, in this Trial, we will conduct longitudinal long-term assessment of donors and donor controls - for the purpose of assessing the impact of donor hepatectomy and living donation on subsequent health, quality of life, and psycho-social function of donors. We propose to continue the LADR-A2ALL protocol for pre-transplant antiviral treatment of patients with chronic hepatitis C in order to prevent recurrence of hepatitis C in the allograft post-transplant. However, virologic responses in patients infected with genotype 1 HCV are inadequate to boost response in these patients and increase the efficacy of LADR-A2ALL we propose the addition of strategically-targeted-antiviral-therapies against hepatitis C (STAT-C). We also propose to continue the study of return of hepatic function in donors after right lobectomy. In our modified protocol we specifically focus on volumetric studies of liver and spleen, SPECT liver-spleen scan, and dual-isotope-labeled cholate clearances and cholate shunt to assess the physiologic changes after hepatectomy. Two ancillary studies will focus on the long-term outcomes of donors and biliary complications in recipients of LDLT. A key concern of physicians, surgeons, patients and families is whether any aspect of donor health, function, psychological adjustment, or social status is affected by LDLT. Our study will use a combination of clinic visits and assessments coupled with telephone interviews to define donor status over 2 years post-hepatectomy. Recent publications and our own analyses suggest that biliary complications are more common and more severe in LDLT recipients. In our ancillary study of biliary complications, we will compare and contrast biliary complications and outcomes between LDLT and DDLT recipients.

Public Health Relevance

The Colorado Transplant Center aims to define a number of key issues in LDLT - long-term outcomes of LDLT, compared to DDLT, efficacy and safety of pre-transplant antiviral therapy, changes in donor hepatic mass and hepatic function after right lobectomy, long-term followup of donors and matched potential-donor controls, and incidence and severity of biliary complications after LDLT. Methods will include CT or MRI measurement of liver volume. SPECT liver-spleen scan, stable isotopes, and LC/MS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK062536-11
Application #
8330875
Study Section
Special Emphasis Panel (ZDK1-GRB-8 (O2))
Program Officer
Sherker, Averell H
Project Start
2002-09-17
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
11
Fiscal Year
2012
Total Cost
$134,786
Indirect Cost
$88,743
Name
University of Colorado Denver
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
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
Gordon, Fredric D; Goldberg, David S; Goodrich, Nathan P et al. (2016) Recurrent primary sclerosing cholangitis in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study: Comparison of risk factors between living and deceased donor recipients. Liver Transpl 22:1214-22
Samstein, B; Smith, A R; Freise, C E et al. (2016) Complications and Their Resolution in Recipients of Deceased and Living Donor Liver Transplants: Findings From the A2ALL Cohort Study. Am J Transplant 16:594-602
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
Pomposelli, James J; Goodrich, Nathan P; Emond, Jean C et al. (2016) Patterns of Early Allograft Dysfunction in Adult Live Donor Liver Transplantation: The A2ALL Experience. Transplantation 100:1490-9
Olthoff, Kim M; Smith, Abigail R; Abecassis, Michael et al. (2015) Defining long-term outcomes with living donor liver transplantation in North America. Ann Surg 262:465-75; discussion 473-5
DiMartini, Andrea F; Dew, Mary Amanda; Butt, Zeeshan et al. (2015) Patterns and predictors of sexual function after liver donation: The Adult-to-Adult Living Donor Liver Transplantation Cohort study. Liver Transpl 21:670-82
Olthoff, Kim M; Emond, Jean C; Shearon, Tempie H et al. (2015) Liver regeneration after living donor transplantation: adult-to-adult living donor liver transplantation cohort study. Liver Transpl 21:79-88
Smith, Abigail R; Schaubel, Douglas E (2015) Time-dependent prognostic score matching for recurrent event analysis to evaluate a treatment assigned during follow-up. Biometrics 71:950-9
Ladner, Daniela P; Dew, Mary Amanda; Forney, Sarah et al. (2015) Long-term quality of life after liver donation in the adult to adult living donor liver transplantation cohort study (A2ALL). J Hepatol 62:346-53

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