Adult-to-Adult Living Donor Transplant Cohort Study

NCT01619475 | Completed DMC

• 12 other identifiers: A2ALL Core ProtocolU01DK085587U01DK085563U01DK085515U01DK062536U01DK062531U01DK062498U01DK062494U01DK062483U01DK062467U01DK0624445U01DK062498-09
• Study Type: observational
• Target: 1,871
• Locations: 2 countries
• Sites: 9

Brief Summary

The study is being conducted for the following reasons:

1. 1.To determine the prevalence, course, and predictors of poor Health Related Quality of Life (HRQOL) outcomes associated with living donor donation.
2. 2.To collect data and biosamples prior to, during, and after a living donor liver transplant (LDLT) among all donors and recipients for use by other adult-to-adult living donor liver transplant studies and future studies.
3. 3.To study the effects of pressure and flow on the outcomes of LDLT.
4. 4.To characterize the differences between living donor liver transplant and deceased donor liver transplant in terms of recipient post-transplant outcomes including patient and graft survival, surgical morbidity, and resource utilization.
5. 5.To compare the long-term histological outcomes in recipients of LDLT and deceased donor liver transplant (DDLT) with recurrent hepatitis C virus (HCV) infection.
6. 6.To understand the history of pain management and to measure quality of care in pain control in living donors following partial hepatectomy.

Conditions

Liver Diseases; Hepatocellular Cancer; End Stage Liver Disease; Hepatitis C; Liver Cirrhosis

Keywords

Living Donor; Liver Transplantation; Quality of Life; Biosamples; Liver Recipient

Outcome Measures

Primary Outcomes (7)

• Recipient patient and graft survival starting from the time of transplantation in LDLT & DDLT.

  To characterize the differences between LDLT and DDLT in terms of recipient post-transplant outcomes for patient and graft survival.

  Yearly follow-up starting at transplant, measured between enrollment and up to 4 years.

• Number and severity of surgical complications and resource utilization after transplant.

  Comparison of incidence of defined medical and surgical complications after transplant between LDLT and DDLT. Comparison of resource utilization (hospitalization) between LDLT and DDLT.

  Yearly follow-up starting at transplant, measured between enrollment , and up to 4 years.

• Health Related Quality of Life (HRQOL) in living liver donors.

  To estimate the prevalence, course, and predictors of poor HRQOL outcomes associated with living liver donation.

  Yearly assessment from donation up to 5 assessments.

• Number of Blood/Tissue Samples from Donors and Recipients.

  To collect data and biosamples prior to, during, and after LDLT among all donors and recipients for use by other A2ALL protocols and future studies.

  Yearly samples starting at transplant/donation (donors until year 1, and recipients until year 4.)

• Pressure and Flow Measurements during the transplant surgery in LDLT recipients.

  To establish normal hepatic blood flow and portal compliance in the human liver, to examine the relationships among hepatic flow and pressure, graft size and function, and clinical outcomes.

  During the transplant (at completion of dissection, and after revascularization).

• Measures of liver fibrosis (Ishak score) in LDLT and DDLT recipients with recurrent HCV infection.

  To assess whether recurrent Hepatitis C is histologically less severe in LDLT compared with DDLT recipients.

  Enrollment up to 4 years, with data collected at the time of each liver biopsy.

• Pain control in living donors following partial hepatectomy

  Self-reported pain and satisfaction with pain management during the first 48 hours after donation surgery.

  The first 48 hours after donation surgery

Study Arms (3)

Prospective

Individuals approved as liver donors and recipients shortly Pre-donation/Pre-transplant at the study sites.

Long-Term Follow-up

Donors and recipients enrolled in the original A2ALL Cohort study. Donors and LDLT recipients whose donation/transplant occurred during the period of time that began with the end of enrollment into the original Cohort study (Aug. 31, 2009) and ended with the opening of the enrollment in the current core protocol; this is referred to as the "Gap Era." LDLT recipients and donors who were not in the original Cohort study or from the Gap Era will enter the study at time proximate to time of living donation.

HCV-Infected Liver Transplant Recipients

Male and female HCV-infected adult liver transplant recipients from those enrolled in the A2ALL-1 Cohort study and from those concurrently transplanted at the new A2ALL-2 centers (University of Toronto, University of Pittsburgh, Lahey Clinic).

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The sample population will consist of the following: * Donors and LDLT and DDLT recipients enrolled in the original A2ALL cohort study. * Donors and LDLT recipients where the donation/transplant occurred during the period of time that began with the end of enrollment into the original Cohort study (August 31, 2009) and ended with the opening of enrollment in the current core protocol; this is referred to as the "Gap Era." * Prospective donors and LDLT recipients for donation/transplant surgery. * HCV-infected adult liver transplant recipients enrolled in the A2ALL-1 Cohort and from those currently transplanted at the new A2ALL-2 centers (University of Toronto, University of Pittsburgh, and Lahey Clinic).

You may qualify if:

• Recipients
• Age 18 or older at the time of consent
• Has had a living donor identified and accepted and LDLT is planned
• Informed consent obtained
• Is listed for single organ (liver) transplantation
• Donors
• Age 18 or older at the time of consent
• Has undergone donor evaluation process and was accepted and donation surgery is planned
• Informed consent obtained

You may not qualify if:

• None

Sponsors & Collaborators

• Arbor Research Collaborative for Health: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (9)

University of California

San Francisco, California, 94143, United States

Location

University of Colorado Health Sciences

Aurora, Colorado, 80045, United States

Location

Northwestern University, Division of Transplantation

Chicago, Illinois, 60611, United States

Location

Lahey Clinic

Burlington, Massachusetts, 01805, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Virginia Commonwealth University-Medical College of Virginia

Richmond, Virginia, 23298, United States

Location

University of Toronto

Toronto, Ontario, M5G 2N2, Canada

Location

Related Publications (35)

• Olthoff KM, Merion RM, Ghobrial RM, Abecassis MM, Fair JH, Fisher RA, Freise CE, Kam I, Pruett TL, Everhart JE, Hulbert-Shearon TE, Gillespie BW, Emond JC; A2ALL Study Group. Outcomes of 385 adult-to-adult living donor liver transplant recipients: a report from the A2ALL Consortium. Ann Surg. 2005 Sep;242(3):314-23, discussion 323-5. doi: 10.1097/01.sla.0000179646.37145.ef.

  PMID: 16135918 BACKGROUND

• Freise CE, Gillespie BW, Koffron AJ, Lok AS, Pruett TL, Emond JC, Fair JH, Fisher RA, Olthoff KM, Trotter JF, Ghobrial RM, Everhart JE; A2ALL Study Group. Recipient morbidity after living and deceased donor liver transplantation: findings from the A2ALL Retrospective Cohort Study. Am J Transplant. 2008 Dec;8(12):2569-79. doi: 10.1111/j.1600-6143.2008.02440.x. Epub 2008 Oct 24.

  PMID: 18976306 BACKGROUND

• Trotter JF, Hill-Callahan MM, Gillespie BW, Nielsen CA, Saab S, Shrestha R, Talamantes MM, Weinrieb RM; A2ALL Study Group. Severe psychiatric problems in right hepatic lobe donors for living donor liver transplantation. Transplantation. 2007 Jun 15;83(11):1506-8. doi: 10.1097/01.tp.0000263343.21714.3b.

  PMID: 17565325 BACKGROUND

• Trotter JF, Wisniewski KA, Terrault NA, Everhart JE, Kinkhabwala M, Weinrieb RM, Fair JH, Fisher RA, Koffron AJ, Saab S, Merion RM; A2ALL Study Group. Outcomes of donor evaluation in adult-to-adult living donor liver transplantation. Hepatology. 2007 Nov;46(5):1476-84. doi: 10.1002/hep.21845.

  PMID: 17668879 BACKGROUND

• Terrault NA, Shiffman ML, Lok AS, Saab S, Tong L, Brown RS Jr, Everson GT, Reddy KR, Fair JH, Kulik LM, Pruett TL, Seeff LB; A2ALL Study Group. Outcomes in hepatitis C virus-infected recipients of living donor vs. deceased donor liver transplantation. Liver Transpl. 2007 Jan;13(1):122-9. doi: 10.1002/lt.20995.

  PMID: 17192908 BACKGROUND

• Fisher RA, Kulik LM, Freise CE, Lok AS, Shearon TH, Brown RS Jr, Ghobrial RM, Fair JH, Olthoff KM, Kam I, Berg CL; A2ALL Study Group. Hepatocellular carcinoma recurrence and death following living and deceased donor liver transplantation. Am J Transplant. 2007 Jun;7(6):1601-8. doi: 10.1111/j.1600-6143.2007.01802.x.

  PMID: 17511683 BACKGROUND

• Campsen J, Blei AT, Emond JC, Everhart JE, Freise CE, Lok AS, Saab S, Wisniewski KA, Trotter JF; Adult-to-Adult Living Donor Liver Transplantation Cohort Study Group. Outcomes of living donor liver transplantation for acute liver failure: the adult-to-adult living donor liver transplantation cohort study. Liver Transpl. 2008 Sep;14(9):1273-80. doi: 10.1002/lt.21500.

  PMID: 18756453 BACKGROUND

• Ghobrial RM, Freise CE, Trotter JF, Tong L, Ojo AO, Fair JH, Fisher RA, Emond JC, Koffron AJ, Pruett TL, Olthoff KM; A2ALL Study Group. Donor morbidity after living donation for liver transplantation. Gastroenterology. 2008 Aug;135(2):468-76. doi: 10.1053/j.gastro.2008.04.018. Epub 2008 Apr 22.

  PMID: 18505689 BACKGROUND

• Shaked A, Ghobrial RM, Merion RM, Shearon TH, Emond JC, Fair JH, Fisher RA, Kulik LM, Pruett TL, Terrault NA; A2ALL Study Group. Incidence and severity of acute cellular rejection in recipients undergoing adult living donor or deceased donor liver transplantation. Am J Transplant. 2009 Feb;9(2):301-8. doi: 10.1111/j.1600-6143.2008.02487.x. Epub 2008 Dec 15.

  PMID: 19120082 BACKGROUND

• Trotter JF, Gillespie BW, Terrault NA, Abecassis MM, Merion RM, Brown RS Jr, Olthoff KM, Hayashi PH, Berg CL, Fisher RA, Everhart JE; Adult-to-Adult Living Donor Liver Transplantation Cohort Study Group. Laboratory test results after living liver donation in the adult-to-adult living donor liver transplantation cohort study. Liver Transpl. 2011 Apr;17(4):409-17. doi: 10.1002/lt.22246.

  PMID: 21445924 BACKGROUND

• Olthoff KM, Abecassis MM, Emond JC, Kam I, Merion RM, Gillespie BW, Tong L; Adult-to-Adult Living Donor Liver Transplantation Cohort Study Group. Outcomes of adult living donor liver transplantation: comparison of the Adult-to-adult Living Donor Liver Transplantation Cohort Study and the national experience. Liver Transpl. 2011 Jul;17(7):789-97. doi: 10.1002/lt.22288.

  PMID: 21360649 BACKGROUND

• Berg CL, Gillespie BW, Merion RM, Brown RS Jr, Abecassis MM, Trotter JF, Fisher RA, Freise CE, Ghobrial RM, Shaked A, Fair JH, Everhart JE; A2ALL Study Group. Improvement in survival associated with adult-to-adult living donor liver transplantation. Gastroenterology. 2007 Dec;133(6):1806-13. doi: 10.1053/j.gastro.2007.09.004. Epub 2007 Sep 14.

  PMID: 18054553 RESULT

• Abecassis MM, Fisher RA, Olthoff KM, Freise CE, Rodrigo DR, Samstein B, Kam I, Merion RM; A2ALL Study Group. Complications of living donor hepatic lobectomy--a comprehensive report. Am J Transplant. 2012 May;12(5):1208-17. doi: 10.1111/j.1600-6143.2011.03972.x. Epub 2012 Feb 15.

  PMID: 22335782 RESULT

• Berg CL, Merion RM, Shearon TH, Olthoff KM, Brown RS Jr, Baker TB, Everson GT, Hong JC, Terrault N, Hayashi PH, Fisher RA, Everhart JE. Liver transplant recipient survival benefit with living donation in the model for endstage liver disease allocation era. Hepatology. 2011 Oct;54(4):1313-21. doi: 10.1002/hep.24494.

  PMID: 21688284 RESULT

• Butt Z, Dew MA, Liu Q, Simpson MA, Smith AR, Zee J, Gillespie BW, Abbey SE, Ladner DP, Weinrieb R, Fisher RA, Hafliger S, Terrault N, Burton J, Sherker AH, DiMartini A. 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. 2017 May;17(5):1267-1277. doi: 10.1111/ajt.14134. Epub 2017 Jan 3.

  PMID: 27865040 RESULT

• Dew MA, DiMartini AF, Ladner DP, Simpson MA, Pomfret EA, Gillespie BW, Merion RM, Zee J, Smith AR, Holtzman S, Sherker AH, Weinrieb R, Fisher RA, Emond JC, Freise CE, Burton JR Jr, Butt Z. Psychosocial Outcomes 3 to 10 Years After Donation in the Adult to Adult Living Donor Liver Transplantation Cohort Study. Transplantation. 2016 Jun;100(6):1257-69. doi: 10.1097/TP.0000000000001144.

  PMID: 27152918 RESULT

• DiMartini AF, Dew MA, Butt Z, Simpson MA, Ladner DP, Smith AR, Hill-Callahan P, Gillespie BW. Patterns and predictors of sexual function after liver donation: The Adult-to-Adult Living Donor Liver Transplantation Cohort study. Liver Transpl. 2015 May;21(5):670-82. doi: 10.1002/lt.24108.

  PMID: 25779554 RESULT

• DiMartini A, Dew MA, Liu Q, Simpson MA, Ladner DP, Smith AR, Zee J, Abbey S, Gillespie BW, Weinrieb R, Mandell MS, Fisher RA, Emond JC, Freise CE, Sherker AH, Butt Z. 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. 2017 Apr;17(4):1081-1096. doi: 10.1111/ajt.14055. Epub 2016 Nov 10.

  PMID: 27647626 RESULT

• Emond JC, Fisher RA, Everson G, Samstein B, Pomposelli JJ, Zhao B, Forney S, Olthoff KM, Baker TB, Gillespie BW, Merion RM. Changes in liver and spleen volumes after living liver donation: a report from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). Liver Transpl. 2015 Feb;21(2):151-61. doi: 10.1002/lt.24062.

  PMID: 25488878 RESULT

• Emond JC, Goodrich NP, Pomposelli JJ, Baker TB, Humar A, Grant DR, Abt P, Friese CE, Fisher RA, Kam I, Sherker AH, Gillespie BW, Merion RM. Hepatic Hemodynamics and Portal Flow Modulation: The A2ALL Experience. Transplantation. 2017 Oct;101(10):2375-2384. doi: 10.1097/TP.0000000000001823.

  PMID: 28514251 RESULT

• Everson GT, Hoefs JC, Niemann CU, Olthoff KM, Dupuis R, Lauriski S, Herman A, Milne N, Gillespie BW, Goodrich NP, Everhart JE. Functional elements associated with hepatic regeneration in living donors after right hepatic lobectomy. Liver Transpl. 2013 Mar;19(3):292-304. doi: 10.1002/lt.23592.

  PMID: 23239552 RESULT

• Everson GT, Terrault NA, Lok AS, Rodrigo del R, Brown RS Jr, Saab S, Shiffman ML, Al-Osaimi AM, Kulik LM, Gillespie BW, Everhart JE; Adult-to-Adult Living Donor Liver Transplantation Cohort Study. A randomized controlled trial of pretransplant antiviral therapy to prevent recurrence of hepatitis C after liver transplantation. Hepatology. 2013 May;57(5):1752-62. doi: 10.1002/hep.25976. Epub 2013 Jan 17.

  PMID: 22821361 RESULT

• Gillespie BW, Merion RM, Ortiz-Rios E, Tong L, Shaked A, Brown RS, Ojo AO, Hayashi PH, Berg CL, Abecassis MM, Ashworth AS, Friese CE, Hong JC, Trotter JF, Everhart JE; A2ALL Study Group. Database comparison of the adult-to-adult living donor liver transplantation cohort study (A2ALL) and the SRTR U.S. Transplant Registry. Am J Transplant. 2010 Jul;10(7):1621-33. doi: 10.1111/j.1600-6143.2010.03039.x. Epub 2010 Feb 25.

  PMID: 20199501 RESULT

• Gordon FD, Goldberg DS, Goodrich NP, Lok AS, Verna EC, Selzner N, Stravitz RT, Merion RM. 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. 2016 Sep;22(9):1214-22. doi: 10.1002/lt.24496. Epub 2016 Aug 2.

  PMID: 27339253 RESULT

• Kulik LM, Fisher RA, Rodrigo DR, Brown RS Jr, Freise CE, Shaked A, Everhart JE, Everson GT, Hong JC, Hayashi PH, Berg CL, Lok AS; A2ALL Study Group. Outcomes of living and deceased donor liver transplant recipients with hepatocellular carcinoma: results of the A2ALL cohort. Am J Transplant. 2012 Nov;12(11):2997-3007. doi: 10.1111/j.1600-6143.2012.04272.x. Epub 2012 Sep 20.

  PMID: 22994906 RESULT

• Ladner DP, Dew MA, Forney S, Gillespie BW, Brown RS Jr, Merion RM, Freise CE, Hayashi PH, Hong JC, Ashworth A, Berg CL, Burton JR Jr, Shaked A, Butt Z. Long-term quality of life after liver donation in the adult to adult living donor liver transplantation cohort study (A2ALL). J Hepatol. 2015 Feb;62(2):346-53. doi: 10.1016/j.jhep.2014.08.043. Epub 2014 Sep 6.

  PMID: 25195558 RESULT

• Levitsky J, Goldberg D, Smith AR, Mansfield SA, Gillespie BW, Merion RM, Lok AS, Levy G, Kulik L, Abecassis M, Shaked A. Acute Rejection Increases Risk of Graft Failure and Death in Recent Liver Transplant Recipients. Clin Gastroenterol Hepatol. 2017 Apr;15(4):584-593.e2. doi: 10.1016/j.cgh.2016.07.035. Epub 2016 Aug 25.

  PMID: 27567694 RESULT

• Mandell MS, Smith AR, Dew MA, Gordon DB, Holtzman S, Howell T, DiMartini AF, Butt Z, Simpson MA, Ladner DP, Freise CE, McCluskey SA, Fisher RA, Guarrera JV, Olthoff KM, Pomfret EA. Early Postoperative Pain and its Predictors in the Adult to Adult Living Donor Liver Transplantation Cohort Study. Transplantation. 2016 Nov;100(11):2362-2371. doi: 10.1097/TP.0000000000001442.

  PMID: 27517726 RESULT

• Merion RM, Shearon TH, Berg CL, Everhart JE, Abecassis MM, Shaked A, Fisher RA, Trotter JF, Brown RS Jr, Terrault NA, Hayashi PH, Hong JC; A2ALL Study Group. Hospitalization rates before and after adult-to-adult living donor or deceased donor liver transplantation. Ann Surg. 2010 Mar;251(3):542-9. doi: 10.1097/SLA.0b013e3181ccb370.

  PMID: 20130466 RESULT

• Olthoff KM, Emond JC, Shearon TH, Everson G, Baker TB, Fisher RA, Freise CE, Gillespie BW, Everhart JE. Liver regeneration after living donor transplantation: adult-to-adult living donor liver transplantation cohort study. Liver Transpl. 2015 Jan;21(1):79-88. doi: 10.1002/lt.23966. Epub 2014 Oct 6.

  PMID: 25065488 RESULT

• Olthoff KM, Smith AR, Abecassis M, Baker T, Emond JC, Berg CL, Beil CA, Burton JR Jr, Fisher RA, Freise CE, Gillespie BW, Grant DR, Humar A, Kam I, Merion RM, Pomfret EA, Samstein B, Shaked A. Defining long-term outcomes with living donor liver transplantation in North America. Ann Surg. 2015 Sep;262(3):465-75; discussion 473-5. doi: 10.1097/SLA.0000000000001383.

  PMID: 26258315 RESULT

• Pomposelli JJ, Goodrich NP, Emond JC, Humar A, Baker TB, Grant DR, Fisher RA, Roberts JP, Olthoff KM, Gillespie BW, Merion RM. Patterns of Early Allograft Dysfunction in Adult Live Donor Liver Transplantation: The A2ALL Experience. Transplantation. 2016 Jul;100(7):1490-9. doi: 10.1097/TP.0000000000001240.

  PMID: 27326811 RESULT

• Samstein B, Smith AR, Freise CE, Zimmerman MA, Baker T, Olthoff KM, Fisher RA, Merion RM. Complications and Their Resolution in Recipients of Deceased and Living Donor Liver Transplants: Findings From the A2ALL Cohort Study. Am J Transplant. 2016 Feb;16(2):594-602. doi: 10.1111/ajt.13479. Epub 2015 Oct 13.

  PMID: 26461803 RESULT

• Terrault NA, Stravitz RT, Lok AS, Everson GT, Brown RS Jr, Kulik LM, Olthoff KM, Saab S, Adeyi O, Argo CK, Everhart JE, Rodrigo del R; A2ALL Study Group. Hepatitis C disease severity in living versus deceased donor liver transplant recipients: an extended observation study. Hepatology. 2014 Apr;59(4):1311-9. doi: 10.1002/hep.26920. Epub 2014 Mar 1.

  PMID: 24677192 RESULT

• Zimmerman MA, Baker T, Goodrich NP, Freise C, Hong JC, Kumer S, Abt P, Cotterell AH, Samstein B, Everhart JE, Merion RM. Development, management, and resolution of biliary complications after living and deceased donor liver transplantation: a report from the adult-to-adult living donor liver transplantation cohort study consortium. Liver Transpl. 2013 Mar;19(3):259-67. doi: 10.1002/lt.23595.

  PMID: 23495079 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

To collect biosamples prior to, during, and after LDLT among all donors and recipients. These biosamples include, liver biopsy,whole blood for genetic studies and DNA extraction, plasma, serum and peripheral cells to be retained in the bio-repository.

MeSH Terms

Conditions

Liver Diseases; Liver Neoplasms; End Stage Liver Disease; Hepatitis C; Liver Cirrhosis

Condition Hierarchy (Ancestors)

Digestive System Diseases; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Liver Failure; Hepatic Insufficiency; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Robert M Merion, MD

  University of Michigan

  STUDY CHAIR

• Averell Sherker, MD

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2011
• First Posted: June 14, 2012
• Study Start: February 1, 2011
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: February 8, 2019

Record last verified: 2019-02

Locations

CA (1); US (8)