Prostaglandins for adult liver transplanted patients

Cavalcanti, Alexandre Biasi; Vasconcelos, Camila Paiva De; Oliveira, Mariana Perroni de; Rother, Edna Terezinha

doi:10.1002/14651858.cd006006.pub2

Cited by 15 publications

(13 citation statements)

References 36 publications

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“…PGE‐2 administration in liver transplantation has no effect on the rates of allograft dysfunction or patient survival . Data for the effectiveness of PGI‐2 are similarly lacking …”

Section: Therapeutics For Hepatic Irimentioning

confidence: 99%

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Ischaemia reperfusion injury in liver transplantation: Cellular and molecular mechanisms

Dar

Sullivan

Bynon

et al. 2019

Liver International

243

210

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Liver disease causing end organ failure is a growing cause of mortality. In most cases, the only therapy is liver transplantation. However, liver transplantation is a complex undertaking and its success is dependent on a number of factors. In particular, liver transplantation is subject to the risks of ischaemia‐reperfusion injury (IRI). Liver IRI has significant effects on the function of a liver after transplantation. The cellular and molecular mechanisms governing IRI in liver transplantation are numerous. They involve multiple cells types such as liver sinusoidal endothelial cells, hepatocytes, Kupffer cells, neutrophils and platelets acting via an interconnected network of molecular pathways such as activation of toll‐like receptor signalling, alterations in micro‐RNA expression, production of ROS, regulation of autophagy and activation of hypoxia‐inducible factors. Interestingly, the cellular and molecular events in liver IRI can be correlated with clinical risk factors for IRI in liver transplantation such as donor organ steatosis, ischaemic times, donor age, and donor and recipient coagulopathy. Thus, understanding the relationship of the clinical risk factors for liver IRI to the cellular and molecular mechanisms that govern it is critical to higher levels of success after liver transplantation. This in turn will help in the discovery of therapeutics for IRI in liver transplantation – a process that will lead to improved outcomes for patients suffering from end‐stage liver disease.

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“…PGE‐2 administration in liver transplantation has no effect on the rates of allograft dysfunction or patient survival . Data for the effectiveness of PGI‐2 are similarly lacking …”

Section: Therapeutics For Hepatic Irimentioning

confidence: 99%

“…142 Data for the effectiveness of PGI-2 are similarly lacking. 143 TNF-alpha is a central cytokine in hepatic IRI. There are a number of anti-TNF-alpha biologic agents available for use.…”

Section: Ther Apeuti C S For Hepati C Irimentioning

confidence: 99%

Ischaemia reperfusion injury in liver transplantation: Cellular and molecular mechanisms

Dar

Sullivan

Bynon

et al. 2019

Liver International

243

210

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“…The clinical outcome after LT is affected by various donor and recipient characteristics such as graft steatosis, long ischemic period or renal insufficiency prior to LT. In order to define the specific impact of PGI 2 analogue iloprost on liver graft function, a multicenter, randomized, double-blinded clinical trial including an appropriate number of patients is justified [20]. This is the objective of our PRAISE study.…”

Section: Introductionmentioning

confidence: 99%

The PRAISE study: A prospective, multi-center, randomized, double blinded, placebo-controlled study for the evaluation of iloprost in the early postoperative period after liver transplantation (ISRCTN12622749)

Barthel

Rauchfuß

Hoyer³

et al. 2013

BMC Surg

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BackgroundLiver graft dysfunction can deteriorate to complete organ failure and increases perioperative morbidity and mortality after liver transplantation. Therapeutic strategies reducing the rate of graft dysfunction are of current clinical relevance. One approach is the systemic application of prostaglandins, which were demonstrated to be beneficial in reducing ischemia-reperfusion injury. Preliminary data indicate a positive effect of prostacyclin analogue iloprost on allograft viability after liver transplantation. The objective of the study is to evaluate the impact of iloprost in a multi-center trial.Methods/DesignA prospective, double-blinded, randomized, placebo-controlled multicenter study in a total of 365 liver transplant recipients was designed to assess the effect of intravenous iloprost after liver transplantation. Primary endpoint will be the primary graft dysfunction characterized as presentation of one or more of the following criteria: ALAT or ASAT level > 2000 IU/ml within the first 7 postoperative days, bilirubine ≥ 10 mg/dl on postoperative day 7; INR ≥ 1.6 on postoperative day 7 or initial non-function. Secondary endpoints are parameters of post-transplant morbidity, like rates of infections, biliary complications, need of clotting factors or renal replacement therapy and the graft and patient survival.DiscussionA well-established treatment concept to avoid graft dysfunction after liver transplantation does not exist at the moment. If the data of this research project confirm prior findings, iloprost would improve the general outcome after liver transplantation.Trial RegistrationGerman Clinical Trials Register: DRKS00003514. Current Controlled Trials Register: ISRCTN12622749.

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“…Yet, later on, the majority of studies did not support a direct effect of PGE on primary nonfunction. 5,6,8,11,12,14,15 In our study, there was no primary nonfunction event; therefore, the effect of dinoprostone could not be evaluated. Greig et al 13 also showed a more rapid decrease of AST and ALT.…”

Section: Discussionmentioning

confidence: 69%

“…5,8,11,12,14 A 2011 Cochrane analysis reported an important risk of bias in most trials reviewed. 15 An expensive multicenter controlled study should be carried out, yet on a drug that has fairly consistently failed to show benefit, and thus is highly unlikely to be realized.…”

Section: Discussionmentioning

confidence: 99%

The Effect and Safety of Prostaglandin Administration in Pediatric Liver Transplantation

Lironi

Mclin

Wildhaber

2017

Transplantation Direct

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BackgroundProstaglandins are often administered after liver transplantation (LT) to diminish ischemia-reperfusion injury (IRI), to favor liver recovery and to prevent vascular thrombosis. Possible beneficial effects in adult liver recipients are controversial, but the single existing pediatric small case series shows no significant impact of prostaglandin administration after LT. The purpose of this study was to analyze the effect of the prostaglandin dinoprostone in pediatric liver recipients.MethodsA retrospective analysis of 41 children (<16 years) who underwent LT between March 2008 and December 2013 was performed. Dinoprostone was administered at a rate from 0.1 to a maximum of 0.6 μg/kg per hour immediately after LT and for a maximum of 5 days. Effect of dinoprostone on post-LT IRI and hepatic function up to 60 postoperative days and number of hypotensive episodes were analyzed.ResultsThe median cumulative dose of dinoprostone was 28 μg/kg (interquartile range, 23.2). Dinoprostone had no significant effect on post-LT liver function tests and factor V levels at any of the administered dosages. There was no significant association between the total quantity of vasopressor given and the number of hypotensive episodes observed in 8 patients. One patient showed a short-lasting hypotension, possibly related to the administration of dinoprostone.ConclusionsThis study did not show, at any dosage between 0.1 and 0.6 μg/kg per hour, any differences in beneficial or harmful effects of high- or low-dose dinoprostone administered immediately after pediatric LT on markers of IRI, hepatic function, or hypotension.

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Prostaglandins for adult liver transplanted patients

Cited by 15 publications

References 36 publications

Ischaemia reperfusion injury in liver transplantation: Cellular and molecular mechanisms

Ischaemia reperfusion injury in liver transplantation: Cellular and molecular mechanisms

The PRAISE study: A prospective, multi-center, randomized, double blinded, placebo-controlled study for the evaluation of iloprost in the early postoperative period after liver transplantation (ISRCTN12622749)

The Effect and Safety of Prostaglandin Administration in Pediatric Liver Transplantation

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