Double-blind placebo-controlled randomized trial of N-acetylcysteine infusion following live donor liver transplantation

Thirunavayakalathil, Mohammed Abdullatheef; Varghese, Christi Titus; Bharathan, Viju Kumar; Chandran, Biju; Nair, Krishnanunni; Mallick, Shweta; Mathew, Johns Shaji; Amma, Binoj Sivasankara Pillai Thankamony; Ramachandran, Riju; Gopalakrishnan, Unnikrishnan; Balakrishnan, Dinesh; Sudheer, O. V.; Sudhindran, S.

doi:10.1007/s12072-020-10109-y

Cited by 11 publications

(8 citation statements)

References 25 publications

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“…However, in the case of CIT greater than 6 h, the use of NAC was associated with lower ALT activities after transplantation [63]. The use of NAC did not reduce the incidence of both EAD and PNF in a randomized trial involving 150 patients undergoing LDLT in India [64]. In another prospective randomized trial, the role of probiotics administered before liver transplantation was assessed.…”

Section: Mitigation Strategiesmentioning

confidence: 99%

Primary Nonfunction and Early Allograft Dysfunction after Liver Transplantation

Masior¹,

Grąt²

2022

Dig Dis

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Background: Despite continuous progress in the field of liver transplantation, considerable proportion of patients still suffer from the post-operative graft dysfunction. Clinically it presents as early graft dysfunction (EAD) and its more severe form defined as primary non-function (PNF). Post-transplant liver dysfunction translates into significantly worse treatment outcomes. Summary: Both entities are multifactorial, with donor (graft), recipient and procedure related factors playing the key roles. Ischemia reperfusion injury (IRI) is a major driver of their development. So far, various non-invasive (pharmacological) and invasive strategies have been tested to mitigate its negative effects. This article presents current approach to diagnosis, prediction and management of EAD and PNF. Key messages: Different pharmacological interventions may be considered to improve graft function after liver transplantation. Machine perfusion seems to be the most effective method at the moment.

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Section: Mitigation Strategiesmentioning

confidence: 99%

Primary Nonfunction and Early Allograft Dysfunction after Liver Transplantation

Masior¹,

Grąt²

2022

Dig Dis

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“…The FDA approved drug N-acetylcysteine (NAC) is an antioxidant and glutathione inducer indicated for the treatment of fulminant liver failure due to paracetamol overdose 11 . NAC has also been utilized for ameliorating hepatocyte damage in IRI experimental models, while more clinic outcome data is required before the routine use of NAC 12 , 13 . Recently, accumulating evidence reveals that nitric oxide (NO) plays diverse roles in modulating cell behaviors and NO-releasing materials have been designed for potential therapeutic applications 14 – 18 .…”

Section: Introductionmentioning

confidence: 99%

Protective effect of platinum nano-antioxidant and nitric oxide against hepatic ischemia-reperfusion injury

Shi

et al. 2022

Nat Commun

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Therapeutic interventions of hepatic ischemia-reperfusion injury to attenuate liver dysfunction or multiple organ failure following liver surgery and transplantation remain limited. Here we present an innovative strategy by integrating a platinum nanoantioxidant and inducible nitric oxide synthase into the zeolitic imidazolate framework-8 based hybrid nanoreactor for effective prevention of ischemia-reperfusion injury. We show that platinum nanoantioxidant can scavenge excessive reactive oxygen species at the injury site and meanwhile generate oxygen for subsequent synthesis of nitric oxide under the catalysis of nitric oxide synthase. We find that such cascade reaction successfully achieves dual protection for the liver through reactive oxygen species clearance and nitric oxide regulation, enabling reduction of oxidative stress, inhibition of macrophage activation and neutrophil recruitment, and ensuring suppression of proinflammatory cytokines. The current work establishes a proof of concept of multifunctional nanotherapeutics against ischemia-reperfusion injury, which may provide a promising intervention solution in clinical use.

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“…23 Finally, 13 studies with 1121 participants were included in the meta-analysis, of which 550 patients received NAC treatment. 15,[22][23][24][25][26][27][28][29][30][31][32][33] The combined search results are shown in Figure 1.…”

Section: Study Descriptionmentioning

confidence: 99%

N-acetylcysteine in the Donor, Recipient, or Both Donor and Recipient in Liver Transplantation: A Systematic Review With Meta-analysis and Trial Sequential Analysis

et al. 2023

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Background. N-acetylcysteine (NAC) is a potentially effective drug for treating ischemia–reperfusion injury in transplanted livers, but its effect remains controversial. Methods. A systematic review and meta-analysis of relevant clinical trials published and registered in the Cochrane Library, MEDLINE, EMBASE, ClinicalTrial.gov, WHO ICTRP, etc, before March 20, 2022 were conducted and registered with PROSPERO (CRD42022315996). Data were pooled using a random effects model or a fixed effects model based on the amount of heterogeneity. Results. Thirteen studies with 1121 participants, 550 of whom received NAC, were included. Compared with the control, NAC significantly reduced the incidence of primary graft nonfunction (relative risk [RR], 0.27; 95% confidence interval [CI], 0.08-0.96), the incidence of postoperative complications (RR, 0.52; 95% CI, 0.41-0.67), the peak postoperative aspartate transferase level (mean difference [MD], −267.52; 95% CI, −345.35 to −189.68), and the peak alanine transferase level (MD, −293.29; 95% CI, −370.39 to −216.20). NAC also improved 2-y (RR, 1.18; 95% CI, 1.01-1.38) graft survival rate. However, NAC increased the intraoperative cryoprecipitate (MD, 0.94; 95% CI, 0.42-1.46) and red blood cell (MD, 0.67; 95% CI, 0.15-1.19) requirements. Moreover, NAC was administered in various modes in these studies, including to the donor, recipient, or both. Subgroup analysis and network meta-analysis showed that NAC administration to recipients could play a more significant role than the other 2 administration modes. Conclusions. Our study supports the protective effect of NAC against LT-induced ischemia–reperfusion injury and shows better clinical outcomes of NAC administration to recipients.

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Double-blind placebo-controlled randomized trial of N-acetylcysteine infusion following live donor liver transplantation

Cited by 11 publications

References 25 publications

Primary Nonfunction and Early Allograft Dysfunction after Liver Transplantation

Primary Nonfunction and Early Allograft Dysfunction after Liver Transplantation

Protective effect of platinum nano-antioxidant and nitric oxide against hepatic ischemia-reperfusion injury

N-acetylcysteine in the Donor, Recipient, or Both Donor and Recipient in Liver Transplantation: A Systematic Review With Meta-analysis and Trial Sequential Analysis

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