Mechanisms of Parenteral Nutrition–Associated Liver and Gut Injury

Abstract

Parenteral nutrition (PN) has revolutionized the care of patients with intestinal failure by providing nutrition intravenously. Worldwide, PN remains a standard tool of nutrition delivery in neonatal, pediatric, and adult patients. Though the benefits are evident, patients receiving PN can suffer serious cholestasis due to lack of enteral feeding and sometimes have fatal complications from liver injury and gut atrophy, including PN-associated liver disease or intestinal failure-associated liver disease. Recent studies into gut-systemic cross talk via the bile acid-regulated farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) axis, gut microbial control of the TGR5-glucagon-like peptide (GLP) axis, sepsis, and role of prematurity of hepatobiliary receptors are greatly broadening our understanding of PN-associated injury. It has also been shown that the composition of ω-6/ω-3 polyunsaturated fatty acids given parenterally as lipid emulsions can variably drive damage to hepatocytes and cell integrity. This manuscript reviews the mechanisms for the multifactorial pathogenesis of liver disease and gut injury with PN and discusses novel ameliorative strategies. (Nutr Clin Pract. 2020;35:63-71)

Parenteral Nutrition and Oxidant Load in Neonates

“…The absence of enteral feeding prevents the stimulation of receptors, hormones, and growth factors. It also blocks the normal gut–liver crosstalk by reducing downstream signaling to the liver via portal circulation [ 136 ]. For example, farnesoid X receptor (FXR), a ligand-activated transcription factor, is expressed in the terminal ileum and is regulated by bile acids.…”

“…Exclusive TPN can also cause the favourable growth of Gram-negative, endotoxin-producing bacteria, which can exacerbate systemic bacterial infection. These events can result in the suppression of bile acid transporters, and eventually, hepatic injury by endotoxin- and cytokine-mediated suppression [ 136 ]. Although the mechanisms are complex, the lack of enteral stimulation during TPN feeding can lead to the impaired enterohepatic metabolism of bile acids, leading to profound liver injury and potentially life-threatening sepsis.…”

Fish Oil Enriched Intravenous Lipid Emulsions Reduce Triglyceride Levels in Non-Critically Ill Patients with TPN and Type 2 Diabetes. A Post-Hoc Analysis of the INSUPAR Study

“…This could be because the use of ILEs based on pure soybean oil was very low (only three patients, 1.7% of the sample) in our sample. Therefore, even the rest of the formulas used in our study (MCT/LCT, olive oil, and fish oil emulsions) contain variable quantities of n-6 PUFA (but always less than pure soybean oils), and these ILEs could have advantages due to the reduced accumulation of phytosterols and because of the mitigation of the proinflammatory effect of n-6 PUFA, as well as potentiate positive effects of other lipid sources [26].…”

Glucagon-Like Peptide-2 Modulates Enteric Paneth Cells Immune Response and Alleviates Gut Inflammation During Intravenous Fluid Infusion in Mice With a Central Catheter

“…IV infusion is an indispensable method in parenteral nutritional therapy, through which the nutrients needed of patients are supplied. Parenteral nutrition (PN) has been the standardized treatment of patients with acute and/or chronic intestinal failure (1,2). Some diseases make patients unable to tolerate enteral nutrition and can only rely on parenteral nutrition support, such as short bowel syndrome, small bowel resection, Crohn's disease or intestinal ischemia related to thrombosis, volvulus and trauma, intestinal obstruction and radiation enteritis (3).…”

“…Reported, nearly 400,000 patients in the United States rely on parenteral nutrition to survive every year, including more than 1,000 infants with congenital intestinal atresia (5,6). Despite the apparent benefits, patients receiving PN via IV infusion are more likely to develop severe or fatal complications such as liver injury, intestinal atrophy, and immune function suppression (1,2). Other impairments that may occur during PN via IV infusion include damage to the intestinal mucosal barrier, intestinal inflammatory response, increased cytokine release, and gut bacterial translocation (2).…”