Dataset Information

Age Matching of Elderly Liver Grafts With Elderly Recipients Does Not Have a Synergistic Effect on Long-term Outcomes When Both Are Carefully Selected.

ABSTRACT:

Background

Older donors and recipients are increasingly considered for liver transplantation. Both donor and recipient age have a negative impact on outcomes. Large registry analyses show that older donors are frequently matched to older recipients. Whether age-related risks accumulate in a synergic negative effect on outcomes because of donor-recipient age matching is poorly understood.

Methods

We investigated the impact of donor-recipient age interaction on patient and death-censored graft survival in multivariate Cox regressions in 849 transplants (January 2000 to December 2015).

Results

Donors 70 years or older did not affect long-term patient or graft survival. Recipient age independently increased the risk of death (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.02-1.05, P < 0.0001), but donor-recipient age interaction was noninfluential. The negative impact of recipient age on patient survival was significant as early as 6 months after transplantation (HR, 1.06; 95% CI, 1.03-1.09; P = 0.00008). The adjusted risk of death was significant for patients aged 60 to 69 years (HR, 1.995; 95% CI, 1.40-2.85; P < 0.0001) and 70 years or older (HR, 2.001; 95% CI, 1.10-2.66; P = 0.04). In contrast, the risk of graft loss was not influenced by recipient age (HR, 1.02; 95% CI, 0.996-1.04; P = 0.11) or age interaction.

Conclusions

Older livers can be safely used in older recipients without jeopardizing graft and patient survival if other risk factors are minimized.

SUBMITTER: Gilbo N

PROVIDER: S-EPMC6445659 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Publications

Age Matching of Elderly Liver Grafts With Elderly Recipients Does Not Have a Synergistic Effect on Long-term Outcomes When Both Are Carefully Selected.

Gilbo Nicholas N Jochmans Ina I Sainz-Barriga Mauricio M Nevens Frederik F van der Merwe Schalk S Laleman Wim W Verslype Chris C Cassiman David D Verbeke Len L van Malenstein Hannah H Roskams Tania T Pirenne Jacques J Monbaliu Diethard D

Transplantation direct 20190326 4

<h4>Background</h4>Older donors and recipients are increasingly considered for liver transplantation. Both donor and recipient age have a negative impact on outcomes. Large registry analyses show that older donors are frequently matched to older recipients. Whether age-related risks accumulate in a synergic negative effect on outcomes because of donor-recipient age matching is poorly understood.<h4>Methods</h4>We investigated the impact of donor-recipient age interaction on patient and death-cen ...[more]

PMID: 30993187

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Project description:BackgroundThe use of pediatric grafts for liver transplantation (LT) into adult recipients is rare, and reported outcomes are conflicting. The aim of this study is to evaluate the outcomes in adult recipients following LT with grafts from deceased pediatric donors.MethodsA retrospective study identifying adult LT between 2010 and 2020 using pediatric deceased donor liver grafts was conducted. Adults undergoing LT with deceased donor pediatric grafts (age ≤ 12) were identified and matched 1:2 with adults receiving adult grafts (age ≥ 18) based on recipient age (±10 y), model for end-stage liver disease (MELD) score at transplant (±5 points) and etiology of liver disease. To assess real liver size differences between the pediatric-donor and adult-donor groups, patients receiving a graft from a donor between 13 and 17 y were excluded from the main analysis and studied independently. Outcomes between the groups were compared. Complication rates were identified and graded using Clavien-Dindo classification. Graft and patient survival were assessed by Kaplan-Meier curves.ResultsTwelve adult LT recipients with whole liver grafts from deceased pediatric donors were matched with 24 adult recipients of adult donors. Recipient age and MELD score were similar between groups. Recipients of pediatric grafts were more likely to be female (66.7% versus 16.7%, P = 0.007) and leaner (body mass index = 24.4 versus 29.9, P = 0.013). Alcohol-related cirrhosis was the most prevalent liver disease etiology in both groups (P = 0.96). There was no significant difference in length of stay, readmissions, early complications, or major complications between groups. Vascular and biliary complication rates were similar. Actuarial graft and patient survival at 1, 3, and 5 y were 100/100/100 versus 96/96/96 (P = 0.48).ConclusionsExcellent patient and graft survival is achievable with LT using young pediatric deceased donor grafts in smaller adult recipients. Outcomes are comparable with recipients of age and MELD-matched adult donors. Careful donor MELD-score recipient matching and close monitoring for potential biliary and vascular complications are crucial to achieve acceptable outcomes.

Project description:Background: Liver transplantation leads to non-alcoholic fatty liver disease or non-alcoholic steatohepatitis in up to 40% of graft recipients. The aim of our study was to assess transcriptomic profiles of liver grafts and to contrast the hepatic gene expression between the patients after transplantation with vs. without graft steatosis. Methods: Total RNA was isolated from liver graft biopsies of 91 recipients. Clinical characteristics were compared between steatotic (n = 48) and control (n = 43) samples. Their transcriptomic profiles were assessed using Affymetrix HuGene 2.1 ST Array Strips processed in Affymetrix GeneAtlas. Data were analyzed using Partek Genomics Suite 6.6 and Ingenuity Pathway Analysis. Results: The individuals with hepatic steatosis showed higher indices of obesity including weight, waist circumference or BMI but the two groups were comparable in measures of insulin sensitivity and cholesterol concentrations. We have identified 747 transcripts (326 upregulated and 421 downregulated in steatotic samples compared to controls) significantly differentially expressed between grafts with vs. those without steatosis. Among the most downregulated genes in steatotic samples were P4HA1, IGF1, or fetuin B while the most upregulated were PLIN1 and ME1. Most influential upstream regulators included HNF1A, RXRA, and FXR. The metabolic pathways dysregulated in steatotic liver grafts comprised blood coagulation, bile acid synthesis and transport, cell redox homeostasis, lipid and cholesterol metabolism, epithelial adherence junction signaling, amino acid metabolism, AMPK and glucagon signaling, transmethylation reactions, and inflammation-related pathways. The derived mechanistic network underlying major transcriptome differences between steatotic samples and controls featured PPARA and SERPINE1 as main nodes. Conclusions: While there is a certain overlap between the results of the current study and published transcriptomic profiles of non-transplanted livers with steatosis, we have identified discrete characteristics of the non-alcoholic fatty liver disease in liver grafts potentially utilizable for the establishment of predictive signature.

Project description:In hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infected patients, HIV enhances HCV replication and liver damage. Several microRNAs (miRNAs), active in pro-fibrotic and inflammatory pathways, have been implicated in the pathogenesis of this phenomenon. However, these miRNAs have been tested only in explanted cirrhotic livers, when the liver damage has become chronic and irreversible. No data are available on the early phase of viral infection, such as early after liver transplantation (LT). In the present study, the expression of miR-101, miR-122, miR-155, miR-192, miR-200c, miR-338, and miR-532 was determined by quantitative real-time polymerase chain reaction in liver biopsies of HCV (n = 19) and HCV/HIV-infected (n = 20) LT recipients, as well as in a control group (n = 18) of noninfected patients, transplanted for alcoholic cirrhosis. The timing of liver biopsy was 6 months post-LT. None of the patients was treated with direct-acting anti-HCV drugs. All co-infected recipients had suppressed HIV viral load. Grading and staging were assessed according to the Ishak Classification. HCV and HIV viral load were measured in the sera. miR-101 (p = .03), miR-122 (p = .012), and miR-192 (p = .038) were significantly downregulated in HCV/HIV co-infected and HCV mono-infected recipients when compared with noninfected recipients, and such downregulation was more pronounced in co-infected ones. Moreover, in co-infected recipients but not in mono-infected ones, miR-101 inversely correlated with the peripheral HCV-RNA levels (r = .41, p = .04) and miR-122 inversely correlated with peripheral HCV-RNA levels (r = .49, p = .03) and with the histological grading (r = .51, p = .02). In conclusion, as early as 6 months after LT, the presence of HIV-HCV co-infection enhanced a significant downregulation of certain miRNAs that showed a direct correlation with HCV viral load and liver inflammation.

Dataset Information

Age Matching of Elderly Liver Grafts With Elderly Recipients Does Not Have a Synergistic Effect on Long-term Outcomes When Both Are Carefully Selected.

Background

Methods

Results

Conclusions

Publications

Age Matching of Elderly Liver Grafts With Elderly Recipients Does Not Have a Synergistic Effect on Long-term Outcomes When Both Are Carefully Selected.

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