Current Insights Regarding Intestinal Failure-Associated Liver Disease (IFALD): A Narrative Review

Abstract

Intestinal failure-associated liver disease (IFALD) is a spectrum of liver disease including cholestasis, biliary cirrhosis, steatohepatitis, and gallbladder disease in patients with intestinal failure (IF). The prevalence of IFALD varies considerably, with ranges of 40–60% in the pediatric population, up to 85% in neonates, and between 15–40% in the adult population. IFALD has a complex and multifactorial etiology; the risk factors can be parenteral nutrition-related or patient-related. Because of this, the approach to managing IFALD is multidisciplinary and tailored to each patient based on the etiology. This review summarizes the current knowledge on the etiology and pathophysiology of IFALD and examines the latest evidence regarding preventative measures, diagnostic approaches, and treatment strategies for IFALD and its associated complications.

Investigation of parenteral nutrition-induced hepatotoxicity using human liver spheroid co-cultures

“…Among those, lipotoxicity is one of the most documented observations related to the composition of lipid emulsions (i.e.,, phytosterol content, omega-6 fatty acid content), which contribute to liver injury (Driscoll 2023). Other IFALD mechanisms are those linked to glucose toxicity as well as injury mediated by micronutrient toxicity (e.g., manganese, copper, aluminum) or nutrient deficiency (e.g., carnitine, choline, vitamin E) (Howard et al 2007;Gabe and Culkin 2010;Berlana 2022;Zafirovska et al 2023). Liver damage also seems to be dictated by the patient's health status including lack of enteral feeding, gut dysbiosis, short bowel syndrome, central line infections, and immature bile acid metabolism and enterohepatic circulation occurring in preterm neonates (Di Dato et al 2022;Rosseel et al 2023;Zafirovska et al 2023).…”

“…Thus far, IFALD has been mainly investigated in clinical patients and animal experimentation. Despite providing crucial insight into pathophysiology, clinical studies are often conducted in patients with underlying pathological conditions, which challenges the distinction between driving mechanisms and causes (Zafirovska et al 2023;Tabone et al 2024). TPN-related animal research has primarily focused on the use of surgical and preterm rodent and pig models, which has provided critical findings on pathophysiological processes underlying liver injury in the context of IFALD (Sangild et al 2014;Burrin et al 2020).…”

Acquired Zinc Deficiency in Preterm Infant Post-Surgery for Necrotizing Enterocolitis (NEC) on Prolonged Total Parenteral Nutrition (TPN)

“…IFALD is one of the commonest serious complications of long term PN that results in liver injury due to intestinal failure (IF). It has complicated and multivariate causes and consists of a spectrum of liver illnesses, including cholestasis, biliary cirrhosis, and steatohepatitis [ 17 , 18 , 19 ]. SOLEs used for PN have a high phytosterol content, high ω-6 to ω-3 long-chain polyunsaturated fatty acid (PUFA) ratio, and very low levels of α-tocopherol.…”