Evaluation of bioenergetic and mitochondrial function in liver transplantation

Abstract

Background/Aims We measured changes in mitochondrial function and bioenergetics that occur during ischemia/ reperfusion in fresh liver samples of patients undergoing liver transplantation. These variations correlated with markers of liver function and clinical outcome. Ischemia/reperfusion injury related to liver transplantation affects mitochondrial function and bioenergetics. Experimental studies were conducted to identify the role of bioenergetics and mitochondrial dysfunction. To the best of our knowledge, no investigation of these two factors’ impacts on liver transplantation has been performed. Methods This was a prospective study of 28 patients who underwent liver transplantation. We measured parameters of mitochondrial function and bioenergetics in biopsies performed during the procedure. Results We observed a statistically significant reduction in mitochondrial membrane potential, an increase in lag phase, and decreases in mitochondrial respiration and adenosine triphosphate content ( P <0.010). Higher postoperative aminotransferase peaks correlated with worse mitochondrial function; mitochondrial respiration correlated with arterial lactate ( P <0.010). Conclusions There is a relationship between mitochondrial function and ischemia/reperfusion injury. The future use of these clinical markers as prognostic factors may allow early identification of post-transplant liver failure and may indicate the need to perform a new transplant.

Mitochondrial respiration during normothermic liver machine perfusion predicts clinical outcome

“… 8 , 9 It has been demonstrated that mitochondrial respiration, mitochondrial membrane potential and intracellular adenosine triphosphate (ATP) can determine the liver quality prior of transplantation. 10 However, data from direct assessment of mitochondrial function during MP in humans are scarce.…”

Preservation of Mitochondrial Health in Liver Ischemia/Reperfusion Injury

“…Both parameters could help predict liver function before liver implantation and liver morbidity and mortality after transplantation [ 187 , 188 ]. A clinical study found that poorly performing mitochondria from human patients were correlated with worse complications after liver transplantation [ 189 ].…”

Mecanismos del precondicionamiento regenerativo en hepatectomías subtotales en modelo porcino

“…After the resection of liver mass, an early, almost immediate, drastic decrease of the hepatic concentration of total adenine nucleotides, not necessarily associated with energy consumption or mitochondrial impairment, has been mainly related with the release of ATP by hepatocytes and non-parenchymal cells, and it appears to constitute a relevant trigger for liver regeneration 8,9,17 . Increased energy consumption or bioenergetic impairment at this stage, manifested as decreases of ATP with parallel increases of ADP and AMP or as mitochondrial dysfunction, however, has been related with extended hepatic resections or other conditions associated with impaired hepatocyte proliferation or impending liver failure 12,15,18,19 . As in prior studies and consistent with the development of post-hepatectomy liver failure, pigs undergoing 90% hepatectomies presented an immediate decrease of ATP associated with concomitant increases of ADP and AMP, resulting in decreases of the energy load and of the ATP/ADP ratio that persisted up to the 24-h time point.…”