Hypothermic machine perfusion in liver transplantation

Quillin, Ralph C.; Guarrera, James V.

doi:10.1002/lt.25004

Cited by 32 publications

(21 citation statements)

References 36 publications

(40 reference statements)

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“…Previous studies have confirmed that HOPE could resuscitate DCD livers by renewing the metabolically depleted energy, altering the antioxidative status, relieving the downstream activation of sterile inflammation (29)(30)(31)(32), and regulating shear stress-sensitive factors in the endothelium (33)(34)(35). Current multicenter trials are underway to evaluate the use of portable HOPE devices to maximize organ preservation duration (10). Herein, we used a continuous hypothermic perfusion system and investigated whether the TXNIP/NLRP3 inflammasome pathway was involved in the mechanism of HOPE for the attenuation of IRI in DCD rat livers.…”

mentioning

confidence: 96%

“…Although many studies have demonstrated the safety and efficacy of HOPE, the clinical application of HOPE remains investigational in liver transplantation settings. Therefore, there is a clinical need to identify the factors responsible for the ongoing success of HOPE in liver transplantation (10); however, the exact molecular mechanisms that underlie the graft protection conferred by HOPE have not been elucidated.…”

mentioning

confidence: 99%

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Hypothermic oxygenated perfusion (HOPE) attenuates ischemia/reperfusion injury in the liver through inhibition of the TXNIP/NLRP3 inflammasome pathway in a rat model of donation after cardiac death

Zeng

et al. 2018

FASEB j.

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Hypothermic oxygenated perfusion (HOPE) is a relatively new dynamic preservation procedure that has not been widely implemented in liver transplantation despite its advantages. Improved graft protection is one such advantage offered by HOPE and has been attributed to multiple mechanisms, one of which may be the modulation of the thioredoxin-interacting protein (TXNIP)/NOD-like receptor protein 3 (NLRP3) inflammasome pathway. The TXNIP/NLRP3 inflammasome pathway plays a critical role in sterile inflammation under oxidative stress as a result of ischemia/reperfusion injury (IRI). In the current study, we aimed to investigate the graft protection offered by HOPE and its impact on the TXNIP/NLRP3 inflammasome pathway. To simulate conditions of donation after cardiac death (DCD) liver transplantation, rat livers were exposed to 30 min of warm ischemia after cardiac arrest. Livers were then preserved under cold storage (CS) or with HOPE for 3 h. Livers were then subjected to 1 h of isolated reperfusion. Liver injuries were assessed on the isolated perfusion rat liver model system before and after reperfusion. Compared with the CS group, the HOPE group had a significant reduction in liver injury and improvement in liver function. Our findings also revealed that reperfusion injury induced liver damage and activated the TXNIP/NLRP3 inflammasome pathway in DCD rat livers. Pretreatment of DCD rat livers with HOPE inhibited the TXNIP/NLRP3 inflammasome pathway and attenuated liver IRI. Attenuation of oxidative stress as a result of HOPE led to the down-regulation of the TXNIP/NLRP3 inflammasome pathway and thus offered superior protection compared with the traditional CS method of organ preservation.-He, W., Ye, S., Zeng, C., Xue, S., Hu, X., Zhang, X., Gao, S., Xiong, Y., He, X., Vivalda, S., Li, L., Wang, Y., Ye, Q. Hypothermic oxygenated perfusion (HOPE) attenuates ischemia/reperfusion injury in the liver through inhibition of the TXNIP/NLRP3 inflammasome pathway in a rat model of donation after cardiac death.

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confidence: 96%

mentioning

confidence: 99%

Hypothermic oxygenated perfusion (HOPE) attenuates ischemia/reperfusion injury in the liver through inhibition of the TXNIP/NLRP3 inflammasome pathway in a rat model of donation after cardiac death

Zeng

et al. 2018

FASEB j.

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“…Specifically, hypothermic machine perfusion (HMP) reduces peribiliary gland damage in treated donation after circulatory death livers versus controls . However, at this time, perfusion at cold temperatures lacks a reliable method to assess the energy (adenosine triphosphate) status of the liver, and a consensus regarding a biomarker profile of useable HMP livers has not been reached . At normothermic perfusion temperatures, even with extended preservation times, a marked decrease (~50%) in peak ALT was observed in treated livers compared with static cold storage grafts .…”

Section: Machine Preservation: a New Ex Vivo Delivery System Of Rnai mentioning

confidence: 99%

Gene Silencing With siRNA (RNA Interference): A New Therapeutic Option During Ex Vivo Machine Liver Perfusion Preservation

et al. 2019

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RNA interference (RNAi) is a natural process of posttranscriptional gene regulation that has raised a lot of attention culminating with the Nobel Prize in Medicine in 2006. RNAi‐based therapeutics have been tested in experimental transplantation to reduce ischemia/reperfusion injury (IRI) with success. Modulation of genes of the innate immune system, as well as apoptotic genes, and those involved in the nuclear factor kappa B pathways can reduce liver injury in rodent liver pedicle clamping and transplantation models of IRI. However, in vivo use of RNAi faces limitations regarding the method of administration, uptake, selectivity, and stability. Machine perfusion preservation, a more recent alternative approach for liver preservation showing superior results to static cold preservation, could be used as a platform for gene interference therapeutics. Our group was the first to demonstrate uptake of small interfering RNA (siRNA) during liver machine preservation under both normothermic and hypothermic perfusion. Administering siRNA in the perfusion solution during ex vivo machine preservation has several advantages, including more efficient delivery, lower doses and cost‐saving, and none/fewer side effects to other organs. Recently, the first RNAi drug was approved by the US Food and Drug Administration for clinical use, opening a new avenue for new drugs with different clinical applications. RNAi has the potential to have transformational therapeutic applications in several areas of medicine including transplantation. We believe that machine preservation offers great potential to be the ideal delivery method of siRNA to the liver graft, and future studies should be initiated to improve the clinical applicability of RNAi in solid organ transplantation.

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“…In fact, the safety and feasibility of ex-situ machine preservation have already been demonstrated. First clinical trials suggested reduced morbidity and mortality in recipients of high risk organs that were pretreated with extracorporeal machine perfusion devices [115][116][117] . Just recently, He et al [118] from Guangzhou transplant center presented the first case of "ischemia-free transplantation" of a severely steatotic graft by using normothermic machine perfusion without stopping blood supply, already initiated during donor liver harvesting.…”

Section: Improving Cancer-specific Outcome By Mitigating I/r Injurymentioning

confidence: 99%

Liver transplantation for hepatocellular carcinoma - non-cancer factors and implications for improving outcome beyond standard tumor criteria

Kornberg¹,

Schernhammer²

2018

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How to cite this article: Kornberg A, Schernhammer M. Liver transplantation for hepatocellular carcinoma -non-cancer factors and implications for improving outcome beyond standard tumor criteria. Hepatoma Res 2018;4:60. http://dx. AbstractLiver transplantation (LT) is recognized as best treatment option in patients with early hepatocellular cancer (HCC) in underlying liver cirrhosis. Apart from tumor size and number implemented in the Milan criteria, which are current worldwide standards for patient selection, several biological tumor factors have been identified to affect cancer-specific outcome. In particular, grading and vascular tumor invasions were shown to correlate with aggressive biological tumor behavior and poor survival following LT. Identifying tumors with favorable biology is one important approach for expanding the pool of eligible liver recipients beyond the Milan burden limits. Improving the immunological state and condition for appropriate defense against circulating cancer cell attack may be another important prognostic aspect. Therefore, there is increasing interest in non-cancer factors related to the peritransplant period that may influence the oncological outcome by providing negative immunomodulatory actions. Considering and modulation of these non-HCC factors of prognosis might contribute in safely expanding the HCC LT selection criteria.

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Hypothermic machine perfusion in liver transplantation

Cited by 32 publications

References 36 publications

Hypothermic oxygenated perfusion (HOPE) attenuates ischemia/reperfusion injury in the liver through inhibition of the TXNIP/NLRP3 inflammasome pathway in a rat model of donation after cardiac death

Hypothermic oxygenated perfusion (HOPE) attenuates ischemia/reperfusion injury in the liver through inhibition of the TXNIP/NLRP3 inflammasome pathway in a rat model of donation after cardiac death

Gene Silencing With siRNA (RNA Interference): A New Therapeutic Option During Ex Vivo Machine Liver Perfusion Preservation

Liver transplantation for hepatocellular carcinoma - non-cancer factors and implications for improving outcome beyond standard tumor criteria

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