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Title: Elevated levels of circulating mitochondrial DNA predict early allograft dysfunction in patients following liver transplantation.
Austin Authors: Yoshino, Osamu ;Wong, Boris Ka Leong;Cox, Daniel R A ;Lee, Eunice ;Hepworth, Graham;Christophi, Christopher ;Jones, Robert M ;Dobrovic, Alexander ;Muralidharan, Vijayaragavan ;Perini, Marcos V 
Affiliation: Surgery (University of Melbourne)
Olivia Newton-John Cancer Research Institute
School of Cancer Medicine, LaTrobe University, Bundoora, Victoria, Australia
School of Mathematics and Statistics, The University of Melbourne, Melbourne, Victoria, Australia
Issue Date: 23-Aug-2021
Date: 2021-08-23
Publication information: Journal of Gastroenterology and Hepatology 2021; 36(12): 3500-3507
Abstract: The role of circulating mitochondrial DNA (cmtDNA) in transplantation remains to be elucidated. cmtDNA may be released into the circulation as a consequence of liver injury; yet recent work also suggests a causative role for cmtDNA leading to hepatocellular injury. We hypothesized that elevated cmtDNA would be associated with adverse events after liver transplantation (LT) and conducted an observational cohort study. Twenty-one patients were enrolled prospectively prior to LT. Postoperative complications were observed in 47.6 % (n=10). Seven patients (33.3%) had early allograft dysfunction (EAD) and six patients (28.5%) experienced acute cellular rejection within six months of LT. cmtDNA levels were significantly elevated in all recipients post-LT compared with healthy controls and pre-operative samples (1,361,937 copies/ml [IQR 586,781 - 3,399,687] post-LT; 545,531 copies/ml [IQR 238,562-1,381,015] pre-LT; 194,562 copies/ml [IQR 182,359-231,515] in healthy controls) and returned to normal levels by five days after transplantation. cmtDNA levels were particularly elevated in those who developed EAD in the early post-operative period (p < 0.001). In all patients there was initially a strong overall positive correlation between cmtDNA and plasma hepatocellular enzyme levels (p <0.05). However, the patients with EAD demonstrated a second peak in cmtDNA at post-operative day seven, which did not correlate with liver function tests. The early release of plasma cmtDNA is strongly associated with hepatocellular damage; however, the late surge in cmtDNA in patients with EAD appeared to be independent of hepatocellular injury as measured by conventional tests.
DOI: 10.1111/jgh.15670
ORCID: 0000-0002-0165-1564
Journal: Journal of Gastroenterology and Hepatology
PubMed URL: 34425021
Type: Journal Article
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