Intestinal failure‐associated liver disease: Risks and regression

Total parenteral nutrition (TPN) is a life-saving nutritional therapy in conditions where enteral nutrition is contraindicated or inadequate. However, it has been associated with side effects, one of which is parenteral nutrition–associated liver damage (PNALD). The main features of PNALD are cholestasis, fatty liver disease, and early fibrosis, followed by disease progression, cirrhosis, and liver failure. Risk factors for parenterally fed patients include short bowel syndrome, bacterial overgrowth and translocation, disturbances in hepatobiliary circulation and lack of enteral nutrition, and the choice of an inappropriate fat mixture. The source of the oil present in lipid emulsions is believed to play an important role in the development of long-term complications. This review analyzes the current literature and research on the pathogenesis of PNALD. Likewise, possible options for preventing this complication were discussed.

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“…Diagnosis in adults is based primarily on the elimination of other causes of chronic liver disease or cirrhosis. [2,3,4].…”

Section: Introductionmentioning

confidence: 99%

Liver complications of total parenteral nutrition: the latest therapeutic strategies

Dąbrowska

Zaczek

Majewska

et al. 2023

Postępy Higieny I Medycyny Doświadczalnej

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Administration of antibiotics contributes to cholestasis in pediatric patients with intestinal failure via the alteration of FXR signaling

Xiao

Zhou²,

Lu³

et al. 2018

Exp Mol Med

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The link between antibiotic treatment and IF-associated liver disease (IFALD) is unclear. Here, we study the effect of antibiotic treatment on bile acid (BA) metabolism and investigate the involved mechanisms. The results showed that pediatric IF patients with cholestasis had a significantly lower abundance of BA-biotransforming bacteria than patients without cholestasis. In addition, the BA composition was altered in the serum, feces, and liver of pediatric IF patients with cholestasis, as reflected by the increased proportion of primary BAs. In the ileum, farnesoid X receptor (FXR) expression was reduced in patients with cholestasis. Correspondingly, the serum FGF19 levels decreased significantly in patients with cholestasis. In the liver, the expression of the rate-limiting enzyme in bile salt synthesis, cytochrome P450 7a1 (CYP7A1), increased noticeably in IF patients with cholestasis. In mice, we showed that oral antibiotics (gentamicin, GM or vancomycin, VCM) reduced colonic microbial diversity, with a decrease in both Gram-negative bacteria (GM affected Eubacterium and Bacteroides) and Gram-positive bacteria (VCM affected Clostridium, Bifidobacterium and Lactobacillus). Concomitantly, treatment with GM or VCM decreased secondary BAs in the colonic contents, with a simultaneous increase in primary BAs in plasma. Moreover, the changes in the colonic BA profile especially that of tauro-beta-muricholic acid (TβMCA), were predominantly associated with the inhibition of the FXR and further altered BA synthesis and transport. In conclusion, the administration of antibiotics significantly decreased the intestinal microbiota diversity and subsequently altered the BA composition. The alterations in BA composition contributed to cholestasis in IF patients by regulating FXR signaling.

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Intestinal failure‐associated liver disease: Risks and regression

Abstract: See Article on Page 174

Cited by 2 publications

References 21 publications

Liver complications of total parenteral nutrition: the latest therapeutic strategies

Liver complications of total parenteral nutrition: the latest therapeutic strategies

Administration of antibiotics contributes to cholestasis in pediatric patients with intestinal failure via the alteration of FXR signaling

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