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Unique early gene expression patterns in human adult-to-adult living donor liver grafts compared to deceased donor grafts.

ABSTRACT: Because of inherent differences between deceased donor (DD) and living donor (LD) liver grafts, we hypothesize that the molecular signatures will be unique, correlating with specific biologic pathways and clinical patterns. Microarray profiles of 63 biopsies in 13 DD and 8 LD liver grafts done at serial time points (procurement, backbench and postreperfusion)were compared between groups using class comparisons, network and biological function analyses. Specific genes were validated by quantitative PCR and immunopathology. Clinical findings were also compared. Following reperfusion, 579 genes in DD grafts and 1324 genes in LDs were differentially expressed (p < 0.005). Many upregulated LD genes were related to regeneration, biosynthesis and cell cycle, and a large number of downregulated genes were linked to hepatic metabolism and energy pathways correlating with posttransplant clinical laboratory findings. There was significant upregulation of inflammatory/immune genes in both DD and LD, each with a distinct pattern. Gene expression patterns of select genes associated with inflammation and regeneration in LD and DD grafts correlated with protein expression. Unique patterns of early gene expression are seen in LD and DD liver grafts, correlating with protein expression and clinical results, demonstrating distinct inflammatory profiles and significant downregulation of metabolic pathways in LD grafts.

SUBMITTER: de Jonge J

PROVIDER: S-EPMC2734955 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Unique early gene expression patterns in human adult-to-adult living donor liver grafts compared to deceased donor grafts.

de Jonge J J Kurian S S Shaked A A Reddy K R KR Hancock W W Salomon D R DR Olthoff K M KM

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 20090401 4

Because of inherent differences between deceased donor (DD) and living donor (LD) liver grafts, we hypothesize that the molecular signatures will be unique, correlating with specific biologic pathways and clinical patterns. Microarray profiles of 63 biopsies in 13 DD and 8 LD liver grafts done at serial time points (procurement, backbench and postreperfusion)were compared between groups using class comparisons, network and biological function analyses. Specific genes were validated by quantitati ...[more]

PMID: 19353763

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Project description:BackgroundLiving donor liver transplantation (LDLT) provides an alternative to deceased donor liver transplantation (DDLT) for patients with end-stage liver disease in the circumstance of scarcity of deceased grafts. However, the outcomes of LDLT remain controversial.MethodA systematic review and meta-analysis were performed to compare the outcomes of LDLT with DDLT. Twelve outcomes were assessed.ResultsThirty-nine studies involving 38563 patients were included. LDLT was comparable in red blood cell transfusion, perioperative mortality, length of hospital stay, retransplantation rate, hepatitis C virus recurrence rate, and hepatocellular carcinoma recurrence rate with DDLT. Cold ischemia time was shorter and duration of recipient operation was longer in LDLT. Postoperative intra-abdominal bleeding rate occurred less frequently in LDLT recipients (odds ratio (OR) = 0.64, 95%confidence interval (CI) = 0.46 - 0.88, P = 0.006), but this did not decrease the perioperative mortality. LDLT was associated with significantly higher biliary (OR = 2.23, 95%CI = 1.59 - 3.13, P < 0.00001) and vascular (OR = 2.00, 95%CI = 1.31 - 3.07, P = 0.001) complication rates and better overall survival (OS) (1 year: OR = 1.32, 95%CI = 1.01 - 1.72, P = 0.04; 3 years: OR = 1.39, 95%CI = 1.14 - 1.69, P = 0.0010; and 5 years: OR = 1.33, 95%CI = 1.04 - 1.70, P = 0.02). According to subgroup analysis, biliary complication rate and OS improved dramatically as experience increased, while vascular complication rate could not be improved because it was mainly caused by the difference of the donor type itself.ConclusionsLDLT remains a valuable option for patients in need of liver transplantation for it provides an excellent alternative to DDLT without compromising recipient outcomes. Further refinement in biliary and vascular reconstruction techniques and the accumulation of liver transplantation centers' experience are the key factors in expanding the application of LDLT.

Project description:Adult-to-adult living donors and recipients were studied to characterize patterns of liver growth and identify associated factors in a multicenter study. Three hundred and fifty donors and 353 recipients in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) receiving transplants between March 2003 and February 2010 were included. Potential predictors of 3-month liver volume included total and standard liver volumes (TLV and SLV), Model for End-Stage Liver Disease (MELD) score (in recipients), the remnant and graft size, remnant-to-donor and graft-to-recipient weight ratios (RDWR and GRWR), remnant/TLV, and graft/SLV. Among donors, 3-month absolute growth was 676?±?251 g (mean?±?SD), and percentage reconstitution was 80%?±?13%. Among recipients, GRWR was 1.3%?±?0.4% (8?<?0.8%). Graft weight was 60%?±?13% of SLV. Three-month absolute growth was 549?±?267 g, and percentage reconstitution was 93%?±?18%. Predictors of greater 3-month liver volume included larger patient size (donors and recipients), larger graft volume (recipients), and larger TLV (donors). Donors with the smallest remnant/TLV ratios had larger than expected growth but also had higher postoperative bilirubin and international normalized ratio at 7 and 30 days. In a combined donor-recipient analysis, donors had smaller 3-month liver volumes than recipients adjusted for patient size, remnant or graft volume, and TLV or SLV (P?=?0.004). Recipient graft failure in the first 90 days was predicted by poor graft function at day 7 (HR?=?4.50, P?=?0.001) but not by GRWR or graft fraction (P?>?0.90 for each). Both donors and recipients had rapid yet incomplete restoration of tissue mass in the first 3 months, and this confirmed previous reports. Recipients achieved a greater percentage of expected total volume. Patient size and recipient graft volume significantly influenced 3-month volumes. Importantly, donor liver volume is a critical predictor of the rate of regeneration, and donor remnant fraction affects postresection function. Liver Transpl 21:79-88, 2015. © 2014 AASLD.

Dataset Information

Unique early gene expression patterns in human adult-to-adult living donor liver grafts compared to deceased donor grafts.

Publications

Unique early gene expression patterns in human adult-to-adult living donor liver grafts compared to deceased donor grafts.

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