Perioperative omega-3 fatty acids fail to confer protection in liver surgery: Results of a multicentric, double-blind, randomized controlled trial

Linecker, Michael; Botea, Florin; Raptis, Dimitri A.; Nicolaescu, Diana; Limani, Përparim; Alikhanov, Ruslan; Kim, Pavel; Wirsching, Andrea; Kron, Philipp; Schneider, Marcel; Tschuor, Christoph; Kambakamba, Patryk; Oberkofler, Christian E.; Oliveira, Michelle; Bonvini, John M.; Ефанов, М. Г.; Graf, Rolf; Petrowsky, Henrik; Khatkov, Igor; Clavien, Pierre‐Alain; Popescu, Irinel

doi:10.1016/j.jhep.2019.10.004

Cited by 18 publications

(67 citation statements)

References 28 publications

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“…In some cases, the mortality rate after liver resection is as high as 30% [31]; the posthepatic liver failure represents the single most important cause of death [31,32]. A recent clinical trial with Omega-3 fatty acid infusions failed to confer liver protection in resection surgery, despite its clear liver-directed anti-inflammatory and pro-regenerative action in various rodent models [33]. Hence, it is necessary and urgent to develop new pharmacological intervention targets to improve the liver regeneration capability after PH.…”

Section: Discussionmentioning

confidence: 99%

Islet‐cell autoantigen 69 accelerates liver regeneration by downregulating Tgfbr1 and attenuating Tgfβ signaling in mice

et al. 2020

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Regeneration is a unique defense mechanism of liver tissue in response to functional cell loss induced by toxic chemicals or surgical resection. In this study, we found that Islet‐cell autoantigen 69 (Ica69) accelerates liver regeneration in mice. Following 70% partial hepatectomy, both Ica69 mRNA and protein are significantly upregulated in mouse hepatocytes at the early stage of liver regeneration. Compared with the wild‐type mice, Ica69‐deficient mice have more severe liver injury, delayed liver regeneration, and high surgical accidental mortality following hepatectomy. Mechanistically, Ica69 interacts with Pick1 protein to regulate Tgfbr1 protein expression and Tgfβ‐induced Smad2 phosphorylation. Our findings suggest that Ica69 in liver tissue is a new potential target for promoting liver regeneration.

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Section: Discussionmentioning

confidence: 99%

Islet‐cell autoantigen 69 accelerates liver regeneration by downregulating Tgfbr1 and attenuating Tgfβ signaling in mice

et al. 2020

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“…Whole 45 studies were eligible for further full-text screening, and 36 studies were excluded because they did not meet the inclusion criteria: 7 were not RCTs, 10 were systematic reviews, 5 were letters, and 14 articles lacked the related data. Finally, 9 articles were included in the analysis [21][22][23][24][25][26][27][28][29]. A flow diagram of the search strategy is presented in Figure 1.…”

Section: Literature Search and Study Characteristicsmentioning

confidence: 99%

“…The bias risk of the included studies was assessed using the Cochrane Collaboration risk of bias tool. Seven articles [22,23,[25][26][27][28][29] reported the methods of random sequence generation, 4 studies [22,23,25,27] performed allocation concealment, 8 studies [22][23][24][25][26][27][28][29] described the blinding of participants and personnel, and 6 studies [22,23,25,[27][28][29] considered blinding of outcome assessment. Seven studies [22][23][24][26][27][28][29] reported incomplete outcome data, while the remaining 2 trials [21,25] were considered to have a high risk of attrition bias because of the high dropout rate.…”

Section: Quality Assessmentmentioning

confidence: 99%

“…Seven studies [21,23,24,[26][27][28][29] including 878 patients reported the overall postoperative complications. The meta-analysis showed that immunonutrition significantly reduced the incidence of overall postoperative complications (OR = 0.57, 95% CI: 0.34-0.95; p = 0.03).…”

Section: Effect Of Immunonutrition On Overall Postoperative Complicatmentioning

confidence: 99%

“…However, this study failed to assess clinical outcomes, such as postoperative complications, mortality, and length of hospital stay. In addition, several studies [21][22][23][24][25][26][27][28][29] have been conducted to evaluate the effectiveness of immunonutrition support in patients undergoing liver resection, and they have yielded inconsistent results. Therefore, whether immunonutrition is beneficial and safe for these patients remains undetermined.…”

Section: Introductionmentioning

confidence: 99%

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Clinical Efficacy of Perioperative Immunonutrition Containing Omega-3-Fatty Acids in Patients Undergoing Hepatectomy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

et al. 2020

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Background: The effect of immunonutrition in patients undergoing hepatectomy remains unclear. This meta-analysis aimed to assess the impact of immunonutrition on postoperative clinical outcomes in patients undergoing hepatectomy. Methods: A literature search of PubMed, Cochrane Library, Web of Science, and Embase databases was performed to identify all randomized controlled trials (RCTs) exploring the effect of perioperative immunonutrition in patients undergoing hepatectomy until the end of March 10, 2020. Quality assessment and data extraction of RCTs were conducted independently by 3 reviewers. Mean difference (MD) and odds ratio (OR) with 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model. The meta-analysis was performed with RevMan 5.3 software. Results: Nine RCTs involving a total of 966 patients were finally included. This meta-analysis showed that immunonutrition significantly reduced the incidences of overall postoperative complications (OR = 0.57, 95% CI: 0.34–0.95; p = 0.03), overall postoperative infectious complications (OR = 0.53, 95% CI: 0.37–0.75; p = 0.0003), and incision infection (OR = 0.50, 95% CI: 0.28–0.89; p = 0.02), and it shortened the length of hospital stay (MD = −3.80, 95% CI: −6.59 to −1.02; p = 0.007). There were no significant differences in the incidences of pulmonary infection (OR = 0.60, 95% CI: 0.32–1.12; p = 0.11), urinary tract infection (OR = 1.30, 95% CI: 0.55–3.08; p = 0.55), liver failure (OR = 0.54, 95% CI: 0.23–1.24; p = 0.15), and postoperative mortality (OR = 0.69, 95% CI: 0.26–1.83; p = 0.46). Conclusion: Given its positive impact on postoperative complications and the tendency to shorten the length of hospital stay, perioperative immunonutrition should be encouraged in patients undergoing hepatectomy.

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Exercise Training Decreases Hepatic Injury and Metastases Through Changes in Immune Response to Liver Ischemia/Reperfusion in Mice

et al. 2021

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Background and Aims Liver ischemia/reperfusion injury (IRI) induces local and systemic inflammation in which neutrophil extracellular traps (NETs) are major drivers. IRI markedly augments metastatic growth, which is consistent with the notion that the liver IRI can serve as a premetastatic niche. Exercise training (ExT) confers a sustainable protection, reducing IRI in some animal models, and has been associated with improved survival in patients with cancer; however, the impact of ExT on liver IRI or development of hepatic metastases is unknown. Approach and Results Mice were randomized into exercise (ExT) and sedentary groups before liver IRI and tumor injection. Computerized dynamic network analysis of 20 inflammatory mediators was used to dissect the sequence of mediator interactions after ischemia/reperfusion (I/R) that induce injury. ExT mice showed a significant decrease in hepatic IRI and tissue necrosis. This coincided with disassembly of complex networks among inflammatory mediators seen in sedentary mice. Neutrophil infiltration and NET formation were decreased in the ExT group, which suppressed the expression of liver endothelial cell adhesion molecules. Concurrently, ExT mice revealed a distinct population of infiltrating macrophages expressing M2 phenotypic genes. In a metastatic model, fewer metastases were present 3 weeks after I/R in the ExT mice, a finding that correlated with a marked increase in tumor‐suppressing T cells within the tumor microenvironment. Conclusions ExT preconditioning mitigates the inflammatory response to liver IRI, protecting the liver from injury and metastases. In light of these findings, potential may exist for the reduction of liver premetastatic niches induced by liver IRI through the use of ExT as a nonpharmacologic therapy before curative surgical approaches.

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Perioperative omega-3 fatty acids fail to confer protection in liver surgery: Results of a multicentric, double-blind, randomized controlled trial

Cited by 18 publications

References 28 publications

Islet‐cell autoantigen 69 accelerates liver regeneration by downregulating Tgfbr1 and attenuating Tgfβ signaling in mice

Islet‐cell autoantigen 69 accelerates liver regeneration by downregulating Tgfbr1 and attenuating Tgfβ signaling in mice

Clinical Efficacy of Perioperative Immunonutrition Containing Omega-3-Fatty Acids in Patients Undergoing Hepatectomy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Exercise Training Decreases Hepatic Injury and Metastases Through Changes in Immune Response to Liver Ischemia/Reperfusion in Mice

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