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.

Keywords: liver diseases; microbiome; nutrition support; parenteral nutrition; sepsis; short bowel syndrome.

Figure 1.

Parenteral nutrition–associated injury. (A) During regular enteral nutrition, luminal bile acids activate gut farnesoid X receptor (FXR), releasing fibroblast growth factor 19 (FGF19). (B) FGF19 regulates hepatic cholesterol 7α-hydroxylase (CYP7A1), fat, and glucose metabolism. (C) Gut TGR5 activation by bile acids releases glucagon-like peptide-1 (GLP-1) and GLP-2. (D) GLP-1 modulates hepatic steatosis, insulin, and glucose; GLP-2 modulates gut growth. (E) Gut microbes deconjugate primary bile acids (FXR agonists) to secondary bile acids (TGR5 agonists). (F) Gut microbes also regulate cytokines, interleukins (ILs), and tumor necrosis factor-α (TNF-α), modulating liver and gut injury. FGFR4, FGF receptor 4.