Intestinal failure–associated liver disease: Current challenges in screening, diagnosis, and parenteral nutrition considerations

Abstract

Intestinal failure–associated liver disease (IFALD) is a serious life‐limiting complication that can occur throughout the clinical course of intestinal failure and its management by parenteral nutrition (PN). Despite this, there is a lack of a standardized definition for IFALD, which makes this insidious condition increasingly difficult to screen and diagnose in clinical practice. Attenuating the progression of liver disease before the onset of liver failure is key to improving morbidity and mortality in these patients. This requires timely detection and promptly addressing reversible factors. Although there are various noninvasive tools available to the clinician to detect early fibrosis or cirrhosis in various chronic liver disease states, these have not been validated in the patient population with IFALD. Such tools include biochemical composite scoring systems for fibrosis, transient elastography, and dynamic liver function tests. This review article aims to highlight the existing real need for an accurate, reproducible method to detect IFALD in its early stages. In addition, we also explore the role PN plays in the pathogenesis of this complex multifactorial condition. Various aspects of PN administration have been implicated in the etiology of IFALD, including the composition of the lipid component, nutrient excess and deficiency, and infusion timing. We aim to highlight the clinical relevance of these PN‐associated factors in the development of IFALD and how these can be managed to mitigate the progression of IFALD.

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

“…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).…”