Dataset Information

Metabolomics profiling in acute liver transplant rejection in a pediatric population.

ABSTRACT: Pediatric liver transplantation rejection affects 20% of children. Currently, liver biopsy, expensive and invasive, is the best method of diagnosis. Discovery and validation of clinical biomarkers from blood or other biospecimens would improve clinical care. For this study, stored plasma samples were utilized from two cross-sectional cohorts of liver transplant patients at Children's Healthcare of Atlanta. High resolution metabolic profiling was completed using established methods. Children with (n = 18) or without (n = 25) acute cellular rejection were included in the analysis (n = 43 total). The mean age of these racially diverse cohorts ranged from 12.6 years in the rejection group and 13.6 years in the no rejection group. Linear regression provided 510 significantly differentiating metabolites between groups, and OPLS-DA showed 145 metabolites with VIP > 2. A total of 95 overlapping significant metabolites between OPLS-DA and linear regression analyses were detected. Pathway analysis (p < 0.05) showed bile acid biosynthesis and tryptophan metabolism as the top two differentiating pathways. Network analysis also identified tryptophan and clustered with liver enzymes and steroid use. We conclude metabolic profiling of plasma from children with acute liver transplant rejection demonstrates > 500 significant metabolites. This result suggests that development of a non-invasive biomarker-based test is possible for rejection screening.

SUBMITTER: Frediani JK

PROVIDER: S-EPMC9636214 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Metabolomics profiling in acute liver transplant rejection in a pediatric population.

Frediani Jennifer K JK Beyh Yara S YS Gupta Nitika N Westbrook Adrianna L AL Cleeton Rebecca R Cordero Maria M Hernandez Albert A Tran ViLinh V Jones Dean P DP Vos Miriam B MB

Scientific reports 20221104 1

Pediatric liver transplantation rejection affects 20% of children. Currently, liver biopsy, expensive and invasive, is the best method of diagnosis. Discovery and validation of clinical biomarkers from blood or other biospecimens would improve clinical care. For this study, stored plasma samples were utilized from two cross-sectional cohorts of liver transplant patients at Children's Healthcare of Atlanta. High resolution metabolic profiling was completed using established methods. Children with ...[more]

PMID: 36333377

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Project description:Background & aimsAcute rejection is detrimental to most transplanted solid organs, but is considered to be less of a consequence for transplanted livers. We evaluated risk factors for and outcomes after biopsy-proven acute rejection (BPAR) based on an analysis of a more recent national sample of recipients of liver transplants from living and deceased donors.MethodsWe analyzed data from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) from 2003 through 2014 as the exploratory cohort and the Scientific Registry of Transplant Recipients (SRTR) from 2005 through 2013 as the validation cohort. We examined factors associated with time to first BPAR using multivariable Cox regression or discrete-survival analysis. Competing risks methods were used to compare causes of death and graft failure between recipients of living and deceased donors.ResultsAt least 1 BPAR episode occurred in 239 of 890 recipients in A2ALL (26.9%) and 7066 of 45,423 recipients in SRTR (15.6%). In each database, risk of rejection was significantly lower when livers came from biologically related living donors (A2ALL hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.43-0.76; and SRTR HR, 0.78; 95% CI, 0.66-0.91) and higher in liver transplant recipients with primary biliary cirrhosis, of younger age, or with hepatitis C. In each database, BPAR was associated with significantly higher risks of graft failure and death. The risks were highest in the 12 month post-BPAR period in patients whose first episode occurred more than 1 year after liver transplantation: HRs for graft failure were 6.79 in A2ALL (95% CI, 2.64-17.45) and 4.41 in SRTR (95% CI, 3.71-5.23); HRs for death were 8.81 in A2ALL (95% CI, 3.37-23.04) and 3.94 in SRTR (95% CI, 3.22-4.83). In analyses of cause-specific mortality, associations were observed for liver-related (graft failure) causes of death but not for other causes.ConclusionsContrary to previous data, acute rejection after liver transplant is associated with significantly increased risk of graft failure, all-cause mortality, and graft failure-related death, regardless of primary liver disease etiology. Living donor liver transplantation from a biologically related donor is associated with decreased risk of rejection.

Dataset Information

Metabolomics profiling in acute liver transplant rejection in a pediatric population.

Publications

Metabolomics profiling in acute liver transplant rejection in a pediatric population.

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