Intestinal failure to produce FGF19: A culprit in intestinal failure–associated liver disease?

Abstract

Intestinal failure (IF) is a rare condition that results in severe malabsorption and requires parenteral nutrition (PN) to maintain energy, fluid and electrolyte balance. Neonatal causes of IF include extensive intestinal resections resulting in short bowel syndrome, congenital enteropathies affecting mucosal function and severe intestinal motility disorders due to enteric nerve or muscle dysfunction. In the adult population, IF typically develops after major resection of affected intestine in inflammatory bowel disease or intestinal ischemia. PN is central to the management of IF, ideally serving as a nutritional bridge until intestinal autonomy is restored through intestinal adaptation. Notwithstanding its vital therapeutic importance, PN has been associated with hepatobiliary complications in this setting (i.e. IF-associated liver disease, IFALD) since its introduction in the late 1960s. Children on long-term PN are especially affected by IFALD, with prevalence rates ranging from 22% to 50%. Four percent of all children on PN will eventually die or require intestinal or multivisceral transplantation because of IFALD [1]. In infants, the predominant histological feature of IFALD is cholestasis, which appears to relate to immaturity of the hepatobiliary system and septic complications. In older children and adults, the dominant histological finding is steatosis. Pediatric IFALD can rapidly progress to cirrhosis with all the associated complications. Risk factors for IFALD include prematurity (especially in case of concomitant necrotizing enterocolitis), small bowel bacterial overgrowth, bacterial infections, inability to tolerate any enteral nutrition, and formulation or mode of administration of PN.