Intestinal-Failure-Associated Liver Disease: Beyond Parenteral Nutrition

Abstract

Short bowel syndrome (SBS), usually resulting from massive small bowel resections or congenital defects, may lead to intestinal failure (IF), requiring intravenous fluids and parenteral nutrition to preserve patients' nutritional status. Approximately 15% to 40% of subjects with SBS and IF develop chronic hepatic damage during their life, a condition referred to as intestinal-failure-associated liver disease (IFALD), which ranges from steatosis to fibrosis or end-stage liver disease. Parenteral nutrition has been largely pointed out as the main pathogenetic factor for IFALD. However, other elements, such as inflammation, bile acid metabolism, bacterial overgrowth and gut dysbiosis also contribute to the development of liver damage and may deserve specific treatment strategies. Indeed, in our review, we aim to explore IFALD pathogenesis beyond parenteral nutrition. By critically analyzing recent literature, we seek to delve with molecular mechanisms and metabolic pathways underlying liver damage in such a complex set of patients.

Keywords: Short bowel syndrome; intestinal failure; intestinal-failure-associated liver disease (IFALD); parenteral nutrition.

Figure 1

The imbalance in parenteral nutrition composition contributes to liver injury. Elements in orange have a confirmed role in promoting IFALD; the yellow color refers to elements with a role in preclinical studies, without any available data on humans; the grey color refers to elements with contrasting data from pre-clinical and clinical studies. See the main text for further details. IVFEs: intravenous fat emulsions.

Figure 2

The main pathogenetic factors contributing to the complex pathogenesis of IFALD. FXR: farnesoid-X receptor; TGR5: Takeda-G-protein-coupled receptor 5; GLP-2: glucagon-like peptide-2; DPP4: dipeptidyl peptidase IV.