title: Anti-inflammatory and anti-fibrotic profile of fish oil emulsions used in parenteral nutrition-associated liver disease.
abstract: Home parenteral nutrition (PN) is associated with many complications including severe hepatobiliary dysfunction. Commercial ω-6 fatty acid-soybean based-lipid emulsions in PN may mediate long term PN associate liver disease (PNALD) whereas ω-3-fish oil parenteral emulsions have shown to reverse PNALD in children. However, its clinical effectiveness in adults has been scarcely reported. In this work, we study the role of soybean and fish oil lipid commercial emulsions on inflammatory and profibrotic liver markers in adults with long term PNALD and in in vitro cellular models. Inflammatory and profibrotic markers were measured in serum of ten adults with long term PNALD and in culture supernatants of monocytes. Liver epithelial to mesenchymal transition (EMT) was induced by transforming growth factor beta 1 (TGFβ1) to evaluate in vitro liver fibrosis. Omegaven®, a 100% fish oil commercial emulsion, was infused during four months in two patients with severe long term PNALD reversing, at the first month, the inflammatory, profibrotic and clinical parameters of PNALD. The effect was maintained during the treatment course but impaired when conventional lipid emulsions were reintroduced. The other patients under chronic soybean oil-based PN showed elevated inflammatory and profibrotic parameters. In vitro human monocytes stimulated with lipopolysaccharide induced a strong inflammatory response that was suppressed by Omegaven®, but increased by soybean emulsions. In other experiments, TGFβ1 induced EMT that was suppressed by Omegaven® and enhanced by soybean oil lipid emulsions. Omegaven® improves clinical, anti-inflammatory and anti-fibrotic parameters in adults with long-term home PNALD.
authors.affiliation: Hospital Pharmacy, Clinical Nutrition Unit, University General Hospital Consortium, Valencia, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Pastor-Clerigues
authors.affiliation: Hospital Pharmacy, Clinical Nutrition Unit, University General Hospital Consortium, Valencia, Spain.
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Marti-Bonmati
authors.affiliation: Hospital Pharmacy, Clinical Nutrition Unit, University General Hospital Consortium, Valencia, Spain; Clinical research unit (UIC), University General Hospital Consortium, Valencia, Spain; Research Foundation of General Hospital of Valencia, Valencia, Spain; CIBERES, Health Institute Carlos III, Valencia, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Milara
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Almudever
authors.affiliation: Clinical research unit (UIC), University General Hospital Consortium, Valencia, Spain; Research Foundation of General Hospital of Valencia, Valencia, Spain; Department of Pharmacology, Faculty of Medicine, University of Valencia, Valencia, Spain; CIBERES, Health Institute Carlos III, Valencia, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Cortijo
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D018929:Cell Culture Techniques; D002921:Cicatrix / Q000188:drug therapy / Q000517:prevention & control*; D058750:Epithelial-Mesenchymal Transition; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage*; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage*; D006801:Humans; D008107:Liver Diseases / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D016331:Parenteral Nutrition, Home / Q000009:adverse effects* / Q000379:methods; D013024:Soybean Oil / Q000008:administration & dosage; D014280:Triglycerides
chemical_list: D000893:Anti-Inflammatory Agents; D005217:Fat Emulsions, Intravenous; D043371:Fatty Acids, Omega-6; D005395:Fish Oils; D014280:Triglycerides; C568345:fish oil triglycerides; D013024:Soybean Oil