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Elevated Plasma Levels of Mitochondria-Derived Damage-Associated Molecular Patterns during Liver Transplantation:
Kantoku Nagakawa1, Akihiko Soyama1, Masaaki Hidaka1
1Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences.
Abstract:
The systemic cytokine response during surgery has been reported to be stimulated by the molecules released from damaged cells, called damage-associated molecular patterns (DAMPs). The relationship between DAMPs and liver transplantation has not been reported. We aimed to clarify the relationship between the plasma levels of DAMPs and the short-term post-transplant outcomes, including mortality and postoperative multi-organ dysfunction syndrome (MODS). This retrospective cohort study enrolled 61 patients who underwent liver transplantation. Mitochondrial DNA fragments, as mitochondria-derived DAMPs (mtDAMPs), were isolated from frozen plasma obtained at the start and the end of transplantation and were quantified by polymerase chain reaction. The short-term post-transplant outcomes were compared among the groups categorized based on the median value of the intraoperative fluctuation of mtDAMPs levels. The mtDAMPs levels were increased from the start to the end of transplantation in 52 recipients (85.2%, n = 61). Regarding mortality, no significant differences were noted between the high group (n = 30) and the low group (n = 31). The higher plasma levels of mtDAMPs were correlated with the longer duration of postoperative vasopressor support (P < 0.05). Importantly, the rate of MODS on post-operative day 1 was significantly higher in the high group (high vs. low group: 21 patients [70%] vs. 11 patients [35.1%], P < 0.01). In conclusion, mtDAMPs were increased in plasma during liver transplantation in most recipients. This elevation was not associated with mortality, but associated with the post-transplant recovery. Measuring plasma mtDAMPs may be helpful for predicting posttransplant recovery among liver-transplant recipients.
Insights
Mitochondria-derived damage-associated molecular patterns (mtDAMPs) increase during liver transplants. Elevated mtDAMPs correlate with longer recovery but not mortality, aiding in predicting post-transplant outcomes.
Area of Science:
- Immunology
- Transplantation Surgery
- Biochemistry
Background:
- Systemic cytokine responses during surgery are linked to damage-associated molecular patterns (DAMPs).
- The role of DAMPs in liver transplantation outcomes remains largely unexplored.
- Mitochondrial DNA fragments (mtDAMPs) are a key type of DAMPs.
Purpose of the Study:
- To investigate the relationship between plasma levels of mtDAMPs and short-term outcomes after liver transplantation.
- To assess the association of mtDAMPs with mortality and postoperative multi-organ dysfunction syndrome (MODS).
- To determine if mtDAMPs can predict post-transplant recovery.
Main Methods:
- Retrospective cohort study of 61 liver transplant recipients.
- Quantification of plasma mtDAMPs using polymerase chain reaction at the start and end of transplantation.
- Categorization of patients based on intraoperative fluctuation of mtDAMPs levels to analyze outcomes.
Main Results:
- Plasma mtDAMPs levels increased intraoperatively in 85.2% of recipients.
- No significant difference in mortality was observed between high and low mtDAMPs groups.
- Higher mtDAMPs levels correlated with longer vasopressor support duration and a significantly higher rate of MODS on postoperative day 1.
Conclusions:
- Intraoperative increases in plasma mtDAMPs are common in liver transplantation.
- Elevated mtDAMPs are associated with poorer short-term post-transplant recovery, specifically increased MODS risk, but not mortality.
- Plasma mtDAMPs measurement may serve as a predictive biomarker for post-transplant recovery in liver transplant recipients.
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