Study in Adults on HPN Who Have Developed PNALD Comparing Equivalent Doses of Two Lipid Emulsions: OMEGAVEN 10%®, Enriched in n-3 EFA, and a Standard Lipid Emulsion, Intralipid 20%® Not Enriched in n-3 EFA + Vitamin E Supplement

Background: Parenteral nutrition-associated liver disease (PNALD) in the context of home parenteral nutrition for non-neoplastic chronic intestinal failure is the main metabolic complication of HPN, as reflected by the combined liver and intestine transplantation rate of 45% in adults. Prior to the onset of severe fibrosis, the main basic histological lesions of cholangitis and steatosis evolve in parallel with abnormal liver function tests (LFT), the prevalence of which increases with the duration of HPN. An n-6 polyunsaturated fatty acid lipid supplement, based on soybean oil, has been shown to be a major and independent determinant of PNALD at doses greater than 1 g/kg/infusion.

Study objective: to demonstrate that replacement of the usual lipid emulsion (Intralipid 20%®) at a dose of 0.5 to 1.0 g/kg/PN infusion (n-6:n-3 ratio = 7) by an equivalent dose of a new lipid emulsion, OMEGAVEN 10%®, very rich in n-3 polyunsaturated fatty acids (n-3:n-6 ratio = 7) induces regression of PNALD via the anti-inflammatory and anti-fibrotic effects of n-3 polyunsaturated fatty acids.

Material and methods: The treated population presents with severe chronic non-neoplastic intestinal failure (rare disease), requiring HPN in an accredited centre. The median actuarial risk of PNALD is 50% after 5 years of HPN in adults. PNALD will be defined on inclusion by 2 out of 5 abnormal LFTs: ALT and AST transaminases, conjugated bilirubin, alkaline phosphatase and gamma-glutamyltranspeptidase. This multicentre prospective randomized double-blind study will include patients with no organ failure other than intestinal failure and especially no signs of decompensated cirrhosis on abdominal Doppler ultrasound. It will exclude unstable patients especially as a result of recent infection (<6 weeks). On inclusion, HPN must have been administered for at least 12 weeks and, after inclusion in the study, 6 weeks of HPN will be devoted to standardization of inter-centre practices. To be eligible for inclusion, patients must have a predictable duration of HPN of more than 18 weeks with a degree of dependence ≥ 2 nutritional infusions per week.

Other causes of liver disease will be excluded (viral, autoimmune, alcohol, hepatotoxic drugs, biliary obstruction).

The study duration per patient will be 22 weeks (6 weeks of standardization of HPN, 12 weeks of treatment in one of the two arms and 4 weeks of follow-up). HPN with Intralipid 20%® will be continued unchanged in the HPN control arm and Intralipid 20%® will be replaced by an equivalent dose (0.5 to 1.0 g/kg/Infusion) of OMEGAVEN 10%® up to a maximum dose of 40 mg per infusion due to formulation constraints, in the interventional arm.