Pediatric intestinal failure-associated liver disease.
OBJECTIVE
The goal of this review is to provide updates on the definition, pathophysiology, treatment, and prevention of intestinal failure-associated liver disease (IFALD) that are relevant to care of pediatric patients.


RESULTS
Current literature emphasizes the multifactorial nature of IFALD. The pathogenesis is still largely unknown; however, molecular pathways have been identified. Key to these pathways are proinflammatory cytokines involved in hepatic inflammation and bile acids synthesis such as Toll-like receptor 4 and farnesoid X receptor, respectively. Research for prevention and treatment is aimed at alleviating risk factors associated with IFALD, principally those associated with parental nutrition. Multiple nutrients and amino acids are relevant to the development of IFALD, but lipid composition has been the primary focus. Lipid emulsions with a lower ratio of omega-6-to-omega-3 polyunsaturated fatty acids (FAs) appear to improve bile flow and decrease intrahepatic inflammation. Long-term consequences of these alternative lipid emulsions are yet to be determined.


CONCLUSIONS
IFALD remains the greatest contributor of mortality in patients with intestinal failure. Many factors contribute to its development, namely, alterations in the gut microbiome, sepsis, and lack of enteral intake. Novel combinations of lipid formulations are promising alternatives to purely soy-based formulas to reduce cholestasis.
aDivision of Pediatric Surgery, St. Louis Children's Hospital bDepartment of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.
Cathleen M
CM
Courtney
Brad W
BW
Warner
D002648:Child; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007410:Intestinal Diseases / Q000150:complications* / Q000382:microbiology / Q000503:physiopathology / Q000628:therapy; D008107:Liver Diseases / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy; D010288:Parenteral Nutrition / Q000009:adverse effects / Q000379:methods; D010372:Pediatrics; D012307:Risk Factors