Mitochondrial respiration during normothermic liver machine perfusion predicts clinical outcome

Mészáros, András; Hofmann, Julia; Buch, Madita L.; Cardini, Benno; Dunzendorfer-Matt, Theresia; Nardin, Florian; Blumer, Michael; Fodor, Margot; Hermann, Martin; Zelger, Bettina; Otarashvili, Giorgi; Schartner, Melanie; Weißenbacher, Annemarie; Oberhuber, Rupert; Resch, Thomas; Troppmair, Jakob; Öfner, Dietmar; Zoller, Heinz; Tilg, Herbert; Gnaiger, Erich; Hautz, Theresa; Schneeberger, Stefan

doi:10.1016/j.ebiom.2022.104311

Cited by 13 publications

(8 citation statements)

References 35 publications

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“…Indeed, improving mitochondrial function with machine perfusion leads to improved graft function [ 8 , 187 ]. Machine perfusion allows the monitoring of mitochondrial function and the detection of mitochondrial-related biomarkers [ 187 , 188 ]. Both parameters could help predict liver function before liver implantation and liver morbidity and mortality after transplantation [ 187 , 188 ].…”

Section: Discussionmentioning

confidence: 99%

“…Machine perfusion allows the monitoring of mitochondrial function and the detection of mitochondrial-related biomarkers [ 187 , 188 ]. 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 ].…”

Section: Discussionmentioning

confidence: 99%

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Preservation of Mitochondrial Health in Liver Ischemia/Reperfusion Injury

2023

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Liver ischemia-reperfusion injury (LIRI) is a major cause of the development of complications in different clinical settings such as liver resection and liver transplantation. Damage arising from LIRI is a major risk factor for early graft rejection and is associated with higher morbidity and mortality after surgery. Although the mechanisms leading to the injury of parenchymal and non-parenchymal liver cells are not yet fully understood, mitochondrial dysfunction is recognized as a hallmark of LIRI that exacerbates cellular injury. Mitochondria play a major role in glucose metabolism, energy production, reactive oxygen species (ROS) signaling, calcium homeostasis and cell death. The diverse roles of mitochondria make it essential to preserve mitochondrial health in order to maintain cellular activity and liver integrity during liver ischemia/reperfusion (I/R). A growing body of studies suggest that protecting mitochondria by regulating mitochondrial biogenesis, fission/fusion and mitophagy during liver I/R ameliorates LIRI. Targeting mitochondria in conditions that exacerbate mitochondrial dysfunction, such as steatosis and aging, has been successful in decreasing their susceptibility to LIRI. Studying mitochondrial dysfunction will help understand the underlying mechanisms of cellular damage during LIRI which is important for the development of new therapeutic strategies aimed at improving patient outcomes. In this review, we highlight the progress made in recent years regarding the role of mitochondria in liver I/R and discuss the impact of liver conditions on LIRI.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Preservation of Mitochondrial Health in Liver Ischemia/Reperfusion Injury

2023

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“…Also, beyond Raman technology, surveillance of mitochondrial respiration and other activities has been proposed to predict postliver transplant outcomes. 40,41 That is, it is possible and feasible to monitor mitochondrial activity to characterize liver function.…”

Section: Discussionmentioning

confidence: 99%

“…However, our study was the first to showcase the value of Raman spectroscopy in assaying mitochondrial dysfunction in fibrotic livers and assessing the ameliorative actions of OCA and YS30 on this process. Also, beyond Raman technology, surveillance of mitochondrial respiration and other activities has been proposed to predict postliver transplant outcomes 40,41 . That is, it is possible and feasible to monitor mitochondrial activity to characterize liver function.…”

Section: Discussionmentioning

confidence: 99%

Label‐free Raman spectroscopy for the assessment of liver fibrosis

Cao,

Ma,

et al. 2023

MedComm – Future Medicine

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The enormous incidence and dire consequences of liver fibrosis highlight the need for biologically plausible markers as readouts of pathology and drug efficacy. The classic reference standard for diagnosis of liver fibrosis is histopathological examinations. However, it is burdened by time‐consuming steps, subjectivity, and the static nature of information. Raman spectroscopy is a rapid, objective, and label‐free analytical tool that provides numerous molecular information. Thus, we utilized Raman spectroscopy to characterize the pathological features of liver fibrosis and to evaluate the efficacy of drugs (obeticholic acid [OCA] and gigantol [YS30]). Principal component analysis with subsequent linear discriminant analysis could basically discriminate between fibrotic mice and healthy controls and showed that animals with OCA or YS30 treatment resembled those with vehicle treatment. Moreover, we identified several potential biomarkers, including cytochrome C, for liver fibrosis development based on their Raman “fingerprints.” Raman imaging provided quantitative and spatial distribution of collagen and cytochrome C in situ. In addition, we demonstrated the role of OCA or YS30 in revitalizing mitochondrial function to alleviate liver fibrosis using Raman spectroscopy. Collectively, Raman spectroscopy succeeded in tracking liver fibrosis progression, assessing drug efficacy, and yielding significant molecular information useful for quantitatively linking pathological assessment and mechanism of drug action.

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“…Identification and definition of the relevant parameters and their cut-offs are ongoing, but a recently published study that used 203 NMP perfused livers identified alanine transaminase and lactate after 2 hours and peak bile pH and supplementary bicarbonate levels to keep the perfusate within 11 to 29 mmol at pH > 7.2 in the first 4 hours as the strongest predictors of the outcome in a multivariate analysis [33]. In-depth assessment of mitochondrial markers in 50 NMP livers revealed that the markers of mitochondrial integrity and viability correlated with clinical outcomes [34].…”

Section: Normothermic Mpmentioning

confidence: 99%

The Current Role and Future Applications of Machine Perfusion in Liver Transplantation

Staubli¹,

Ceresa²,

Pollok³

2023

Preprint

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The relative paucity of donor livers suitable for transplantation has sparked innovations to preserve and recondition organs to expand the pool of transplantable organs. Currently, machine perfusion techniques have led to the improvement of the quality of marginal livers and to prolonged cold ischemia time and allowed for the prediction of graft function through analysis of the organ during perfusion, improving the rate of organ use. In the future, the implementation of organ modulation might expand the scope of machine perfusion beyond its current usage. The aim of this review was to provide an overview of the current clinical use of machine perfusion devices in liver transplantation and provide a perspective for future clinical use, including therapeutic interventions in perfused donor liver grafts.

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Mitochondrial respiration during normothermic liver machine perfusion predicts clinical outcome

Cited by 13 publications

References 35 publications

Preservation of Mitochondrial Health in Liver Ischemia/Reperfusion Injury

Preservation of Mitochondrial Health in Liver Ischemia/Reperfusion Injury

Label‐free Raman spectroscopy for the assessment of liver fibrosis

The Current Role and Future Applications of Machine Perfusion in Liver Transplantation

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