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Serum interleukin-6 and tumor necrosis factor-? are associated with early graft regeneration after living donor liver transplantation.

ABSTRACT: Liver graft regeneration is orchestrated by specific and sequential stimuli, including hepatocyte growth factors, cytokines, and catecholamines. We evaluated the association between preoperative serum cytokines and early liver graft regeneration in human living donor liver transplantation (LDLT).We retrospectively reviewed the data of adult patients who underwent LDLT from January 2010 to December 2014. Serum cytokines, including interleukin (IL)-2, 6, 10, 12, 17, interferon (IFN)-? and tumor necrosis factor (TNF)-? were measured in the recipients 1 day before surgery and on postoperative day (POD) 7. Liver graft volume was estimated using abdominal computed tomography images of the donors and recipients.In total, 226 patients were analyzed in this study. Median preoperative levels of serum cytokines were as follows: IL-2, 0.1 (0.1-1.6) pg/mL; IL-6, 7.3 (0.1-30.2) pg/mL; IL-10, 0.5 (0.1-11.0) pg/mL; IL-12, 0.1 (0.1-0.1) pg/mL; IL-17, 2.0 (0.1-16.4) pg/mL; IFN-?, 3.2 (0.1-16.0) pg/mL; and TNF-?, 9.8 (5.4-17.9) pg/mL. Higher preoperative serum levels of IL-6, IL-10, and TNF-?, dichotomized at the median, were associated with increased relative liver volumes by POD 7. Multivariate analysis revealed that higher levels of serum IL-6 and TNF-? were independently associated with increased graft volume during the first 1 week after LDLT, based on the lower levels of those cytokines.IL-6 and TNF-? were important mediators of the success of early graft regeneration in patients who underwent LDLT.

SUBMITTER: Chae MS

PROVIDER: S-EPMC5896938 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Serum interleukin-6 and tumor necrosis factor-α are associated with early graft regeneration after living donor liver transplantation.

Chae Min Suk MS Moon Kwang Uck KU Chung Hyun Sik HS Park Chul Soo CS Lee Jaemin J Choi Jong Ho JH Hong Sang Hyun SH

PloS one 20180412 4

<h4>Background</h4>Liver graft regeneration is orchestrated by specific and sequential stimuli, including hepatocyte growth factors, cytokines, and catecholamines. We evaluated the association between preoperative serum cytokines and early liver graft regeneration in human living donor liver transplantation (LDLT).<h4>Patients and methods</h4>We retrospectively reviewed the data of adult patients who underwent LDLT from January 2010 to December 2014. Serum cytokines, including interleukin (IL)-2 ...[more]

PMID: 29649247

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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.

Project description:BackgroundThe reoperation rate remains high after liver transplantation and the impact of reoperation on graft and recipient outcome is unclear. The aim of our study is to evaluate the impact of early reoperation following living-donor liver transplantation (LDLT) on graft and recipient survival.MethodsRecipients that underwent LDLT (n = 111) at the University of Tokyo Hospital between January 2007 and December 2012 were divided into two groups, a reoperation group (n = 27) and a non-reoperation group (n = 84), and case-control study was conducted.ResultsEarly reoperation was performed in 27 recipients (24.3%). Mean time [standard deviation] from LDLT to reoperation was 10 [9.4] days. Female sex, Child-Pugh class C, Non-HCV etiology, fulminant hepatitis, and the amount of intraoperative fresh frozen plasma administered were identified as possibly predictive variables, among which females and the amount of FFP were identified as independent risk factors for early reoperation by multivariable analysis. The 3-, and 6- month graft survival rates were 88.9% (95%confidential intervals [CI], 70.7-96.4), and 85.2% (95%CI, 66.5-94.3), respectively, in the reoperation group (n = 27), and 95.2% (95%CI, 88.0-98.2), and 92.9% (95%CI, 85.0-96.8), respectively, in the non-reoperation group (n = 84) (the log-rank test, p = 0.31). The 12- and 36- month overall survival rates were 96.3% (95%CI, 77.9-99.5), and 88.3% (95%CI, 69.3-96.2), respectively, in the reoperation group, and 89.3% (95%CI, 80.7-94.3) and 88.0% (95%CI, 79.2-93.4), respectively, in the non-reoperation group (the log-rank test, p = 0.59).ConclusionsObserved graft survival for the recipients who underwent reoperation was lower compared to those who did not undergo reoperation, though the result was not significantly different. Recipient overall survival with reoperation was comparable to that without reoperation. The present findings enhance the importance of vigilant surveillance for postoperative complication and surgical rescue at an early postoperative stage in the LDLT setting.

Project description:Simple Summary Acute jaundice, a critical problem after living donor liver transplantation, often required efforts to discriminate its etiologies. MicroRNAs are small non-coding RNAs, which express differently during disease development. To differentiate the etiology of acute jaundice after living donor liver transplantation, we examined hepatic microRNA expression patterns in several liver graft pathologies. Eighty liver transplant recipients undergoing post-transplant liver graft biopsy for the evaluation of acute jaundice were enrolled in this one-year prospective study. Using real-time quantitative reverse transcription-polymerase chain reaction profiling assay, we identified intra-graft microRNA (microRNA-122, microRNA-301, microRNA-133a, and microRNA-21) signatures in various allograft pathologies (37 recipients with acute cholangitis, 20 recipients with acute rejection, 12 recipients with recurrent hepatitis, 6 recipients with non-specific pathological change and 5 recipients with fatty change). In acute cholangitis, intra-graft microRNA-122, microRNA-301, and microRNA-21 significantly down-regulated; in acute rejection, intra-graft microRNA-122 significantly up-regulated and intra-graft microRNA-133a significantly down-regulated; in recurrent hepatitis, intra-graft microRNA-122, microRNA-301, and microRNA-21 remarkably up-regulated; and in fatty change, only intra-graft microRNA-133a up-regulated in significance. Our study suggests that specific intra-graft microRNA expression patterns as a checklist may be helpful for differential diagnosis of acute jaundice etiologies following living donor liver transplantation. Abstract Background: Acute jaundice remains a critical problem following liver transplantation. MicroRNAs (miRNAs) are involved in regulating gene expression related to various disease phenotypes and statuses. Aims: To differentiate acute jaundice etiology after living donor liver transplantation (LDLT), we examined the hepatic miRNA expression patterns in several liver graft pathologies. Methods: Eighty liver transplant recipients undergoing post-LDLT graft biopsy for the evaluation of acute jaundice were enrolled in this 1-year prospective study. Using a real-time quantitative reverse transcription-polymerase chain reaction profiling assay, we identified hepatic miRNA (miRNA-122, miRNA-301, miRNA-133a, and miRNA-21) signatures in various allografts pathologies. Results: Pathologic findings of the 80 recipients were as follows: acute cholangitis (AC), 37 (46%); acute rejection (AR), 20 (25%); recurrent hepatitis (RH), 12 (15%); non-specific pathological change, 6 (8%); and fatty change (FC), 5 (6%). None of these identified hepatic miRNAs expression pattern was significantly correlated with serum parameters, including neutrophil-lymphocyte ratio. In AC, hepatic miRNA-122, miRNA-301, miRNA-133a, and miRNA-21 expression was significantly downregulated (p < 0.05). MicroRNA-122 expression was elevated in cases of AR and RH (p < 0.05); miRNA-301 and miRNA-21 expression was higher in RH than in AC (p < 0.05); and miRNA-133a expression was higher in FC than in AR (p < 0.05). Conclusions: Our study suggests that specific hepatic miRNA expression patterns as a checklist may be useful for differential diagnosis of acute jaundice following liver transplantation.

Dataset Information

Serum interleukin-6 and tumor necrosis factor-? are associated with early graft regeneration after living donor liver transplantation.

Publications

Serum interleukin-6 and tumor necrosis factor-α are associated with early graft regeneration after living donor liver transplantation.

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