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Updated: Oct 23, 2025
An In Vitro Approach to Study Mitochondrial Dysfunction: A Cybrid Model
Published on: March 9, 2022
Elevated levels of circulating mitochondrial DNA predict early allograft dysfunction in patients following liver
Osamu Yoshino1, Boris Ka Leong Wong2,3, Daniel R A Cox1,2
1Department of Surgery, Austin Health, The University of Melbourne, Melbourne, Victoria, Australia.
Background And Aim:
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.
Methods:
Twenty-one patients were enrolled prospectively prior to LT.
Results:
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 6 months of LT. cmtDNA levels were significantly elevated in all recipients after LT compared with healthy controls and preoperative samples (1 361 937 copies/mL [IQR 586 781-3 399 687] after LT; 545 531 copies/mL [IQR 238 562-1 381 015] before LT; and 194 562 copies/mL [IQR 182 359-231 515] in healthy controls) and returned to normal levels by 5 days 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.
Conclusions:
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.
Insights
Elevated circulating mitochondrial DNA (cmtDNA) after liver transplantation is linked to early allograft dysfunction. A late surge in cmtDNA in these patients suggests a mechanism independent of liver injury.
Area of Science:
- Transplantation immunology
- Mitochondrial medicine
- Hepatology
Background:
- Circulating mitochondrial DNA (cmtDNA) role in liver injury and transplantation is unclear.
- cmtDNA may cause or result from hepatocellular injury.
- Hypothesis: elevated cmtDNA correlates with adverse post-liver transplant events.
Purpose of the Study:
- To investigate the association between cmtDNA levels and adverse events after liver transplantation (LT).
Main Methods:
- Prospective observational cohort study.
- Enrolled 21 patients prior to LT.
- Measured cmtDNA levels pre- and post-LT, and compared with healthy controls.
Main Results:
- Postoperative complications occurred in 47.6% of patients; 33.3% had early allograft dysfunction (EAD).
- cmtDNA levels were significantly elevated post-LT compared to pre-LT and healthy controls, returning to normal by day 5.
- Elevated cmtDNA strongly correlated with EAD (P < 0.001) and initially with hepatocellular enzymes.
- Patients with EAD showed a secondary cmtDNA peak on postoperative day 7, not linked to liver function tests.
Conclusions:
- Early plasma cmtDNA release is associated with hepatocellular damage.
- Late cmtDNA surge in EAD patients appears independent of conventional measures of hepatocellular injury.
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