title: Pathophysiology, prevention, treatment, and outcomes of intestinal failure-associated liver disease.
abstract: BACKGROUND
  Intestinal failure-associated liver disease (IFALD) remains a serious problem in the treatment of infants with nutritional problems and short bowel syndrome.
  
  
  METHODS
  A review of the recent literature from 2010 to 2016, concentrating on articles related to the pathophysiology of IFALD and to outcomes of novel nutritional and pharmacological therapies for neonatal cholestasis in the post-surgical neonate.
  
  
  RESULTS
  The pathophysiology of IFALD relates to an increase sensitivity of the neonatal liver to cholestasis in the non-fed state; prolonged cholestasis almost inevitably results in liver damage which will progress from fibrosis to cirrhosis. Clinically discerned risk factors include premature birth, inflammation, sepsis, disruption of the enterohepatic circulation by creation of a proximal stoma, and the duration and type of parenteral nutritional support. Within the hepatocyte, the regulatory enzyme farsanoid receptor X (FXR) appears to play a pivotal role in the development of cholestasis. Recent studies have shown that its activity is suppressed by sepsis, and by plant phytosterols found in soy-based lipid preparations. This paradigm is reflected in the emerging consensus for the care of post-surgical neonates, which is based around a multi-disciplinary team approach. Using an algorithm-driven approach, an appropriate balance between caloric support and prevention of IFALD can be achieved.
  
  
  CONCLUSIONS
  Further prospective studies are required to further refine the optimal sequence of use of these therapies and the long-term effects on neurological development and hepatic function. However, with optimal care, the number of IF patients progressing to end-stage liver disease because of IFALD should be very low.
authors.affiliation: Department of Pediatric Surgery, Hamad Medical Corporation, Doha, Qatar.
authors.forename: Noora H
authors.initials: NH
authors.lastname: Al-Shahwani
authors.affiliation: Chair of Surgery, Sidra Medical and Research Center, PO Box 26999, Doha, Qatar. dsigalet@sidra.org.|Surgery, Weill Cornell Medicine, New York, NY, USA. dsigalet@sidra.org.|Surgery, Weill Cornell Medicine, Doha, Qatar. dsigalet@sidra.org.
authors.forename: David L
authors.initials: DL
authors.lastname: Sigalet
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002779:Cholestasis / Q000503:physiopathology; D004750:Enteral Nutrition; D005217:Fat Emulsions, Intravenous / Q000627:therapeutic use; D006801:Humans; D007410:Intestinal Diseases / Q000503:physiopathology / Q000628:therapy*; D008107:Liver Diseases / Q000503:physiopathology / Q000517:prevention & control*; D012778:Short Bowel Syndrome / Q000503:physiopathology
chemical_list: D000900:Anti-Bacterial Agents; D005217:Fat Emulsions, Intravenous
keywords: Cirrhosis; Fibrosis; Omegevan; SMOF