Tohoku J. Exp. Med., 2020 February, 250(2)

Elevated Plasma Levels of Mitochondria-Derived Damage-Associated Molecular Patterns during Liver Transplantation: Predictors for Postoperative Multi-Organ Dysfunction Syndrome

KANTOKU NAGAKAWA,¹ AKIHIKO SOYAMA,¹ MASAAKI HIDAKA,¹ TOMOHIKO ADACHI,¹ SHINICHIRO ONO,¹ TAKANOBU HARA,¹ MITSUHISA TAKATSUKI¹ and SUSUMU EGUCHI¹

¹Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Nagasaki, Japan

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.

Keywords —— cytokines; damage-associated molecular patterns (DAMPs); liver transplantation; surgical stress; systemic inflammatory response syndrome (SIRS)

© 2020 Tohoku University Medical Press

===============================

Tohoku J. Exp. Med., 2020, 250, 87-93

Correspondence: Susumu Eguchi, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, Nagasaki 852-8501, Japan.

e-mail: sueguchi@nagasaki-u.ac.jp