Omega-3 fatty acid lipid emulsions are safe and effective in reducing endotoxemia and sepsis in acute-on-chronic liver failure: An open-label randomized controlled trial

J Gastroenterol Hepatol. 2021 Jul;36(7):1953-1961. doi: 10.1111/jgh.15400. Epub 2021 Jan 28.

Abstract

Background and aim: Sepsis is an important determinant of the outcome of acute-on-chronic liver failure (ACLF) patients. Omega-3 fatty acids (FAs) are known to suppress inflammation, reduce morbidity, and mortality in postoperative and critically ill patients. We aimed to evaluate the effect of intravenous omega-6 and omega-3 FA lipid emulsions in ACLF patients.

Methods: Ninety ACLF patients were randomly allocated to three groups: Gr. A received no lipid emulsions, Gr. B received omega-6 FAs, and Gr. C received omega-3 FAs. The primary and secondary aims were to compare the effects of lipid emulsions on immune modulation, the incidence of bacterial sepsis, and mortality at day 28.

Results: The baseline characteristics of the patients were comparable. Serum endotoxin levels remained suppressed by 22% in Gr. C compared with a 4% and 12% rise in Gr. B and A (P < 0.001). Omega-3 FAs also suppressed C-reactive protein levels and neutrophil-to-lymphocyte ratio in Gr. C. Compared with Gr. A, omega-3 FAs reduced sepsis by 86% (HR, 0.14; 95% CI 0.04-0.43; P < 0.001). Omega-3 FAs significantly increased the expression of TLR2 and TLR4 on both CD14+ and CD16+ monocytes, and TLR4, on macrophages and neutrophils. There were no serious adverse events, except transient flushing in 20% and 16.6% of patients receiving omega-6 FAs and omega-3 FAs, respectively.

Conclusion: Omega-3 FAs are safe and effective in reducing systemic inflammation, endotoxemia, and sepsis in patients with ACLF. These lipid emulsions could also be considered as effective sources of immunonutrition in such sick patients.

Keywords: cirrhosis; endotoxin; immunonutrition; intravenous lipids; neutrophil-to-lymphocyte ratio.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acute-On-Chronic Liver Failure*
  • Emulsions
  • Endotoxemia* / etiology
  • Endotoxemia* / prevention & control
  • Fatty Acids, Omega-3*
  • Humans
  • Sepsis* / etiology
  • Sepsis* / prevention & control
  • Toll-Like Receptor 4

Substances

  • Emulsions
  • Fatty Acids, Omega-3
  • Toll-Like Receptor 4