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 6months of LT. cmtDNA levels were significantly elevated in all recipients after LT compared with healthy controls and preoperative samples (1361937 copies/mL [IQR 586781-3399687] after LT; 545531 copies/mL [IQR 238562-1381015] before LT; and 194562 copies/mL [IQR 182359-231515] in healthy controls) and returned to normal levels by 5days after transplantation. cmtDNA levels were particularly elevated in those who developed EAD in the early postoperative 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 postoperative day 7, 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.
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