Emerging role of regulated cell death in intestinal failure-associated liver disease

Abstract

Intestinal failure-associated liver disease (IFALD) is a common complication of long-term parenteral nutrition that is associated with significant morbidity and mortality. It is mainly characterized by cholestasis in children and steatohepatitis in adults. Unfortunately, there is no effective approach to prevent or reverse the disease. Regulated cell death (RCD) represents a fundamental biological paradigm that determines the outcome of a variety of liver diseases. Nowadays cell death is reclassified into several types, based on the mechanisms and morphological phenotypes. Emerging evidence has linked different modes of RCD, such as apoptosis, necroptosis, ferroptosis, and pyroptosis to the pathogenesis of liver diseases. Recent studies have shown that different modes of RCD are present in animal models and patients with IFALD. Understanding the pathogenic roles of cell death may help uncover the underlying mechanisms and develop novel therapeutic strategies in IFALD. In this review, we discuss the current knowledge on how RCD may link to the pathogenesis of IFALD. We highlight examples of cell death-targeted interventions aiming to attenuate the disease, and provide perspectives for future basic and translational research in the field.

Keywords: Apoptosis; Cholestasis; Necroptosis; Parenteral nutrition; Steatosis.