Parenteral Nutrition and Liver Health Management

Parenteral nutrition (PN) is a vital therapeutic strategy for individuals unable to absorb nutrients enterally, offering macronutrients, micronutrients and essential fatty acids directly into the circulation. Despite its life-sustaining benefits, prolonged PN is frequently complicated by liver dysfunction, collectively termed intestinal failure–associated liver disease (IFALD). The pathogenesis of IFALD is multifactorial, implicating lipid emulsion composition, phytosterol accumulation, bile acid transport disruption and inflammatory mediators released by hepatic macrophages. Management strategies focus on optimising the composition of lipid admixtures, introducing fish-oil based emulsions rich in n-3 polyunsaturated fatty acids, and modulating signalling pathways such as farnesoid X receptor (FXR) and nuclear factor-κB (NF-κB). Emerging approaches explore the addition of natural bioactive compounds, targeted pharmacological agonists of nuclear receptors and refined monitoring techniques to detect early hepatic injury. These advances hold promise for reducing cholestasis, steatosis and oxidative stress, thus preserving liver function in patients dependent on long-term PN.

Research from Nature Portfolio

Investigations using a combined intestinal injury and parenteral nutrition mouse model have elucidated the central role of hepatic macrophages and interleukin-1β in driving cholestatic injury. Activation of NF-κB in hepatocytes was shown to suppress transcription of bile and sterol transporters, leading to impaired bile flow and cholestasis. Experimental antagonism of IL-1 signalling or deletion of key inflammasome components prevented liver injury, highlighting macrophage-derived cytokines as therapeutic targets. This foundational work provides a mechanistic framework linking immune mediators with bile acid homeostasis and identifies potential interventions to restore transporter expression and mitigate parenteral nutrition-associated cholestasis.

Parenteral Nutrition and Liver Health Management publication trend

The graph below shows the total number of articles in parenteral nutrition and liver health management across all publications each year (not limited to Nature Index journals).

Technical terms

Parenteral nutrition (PN): Intravenous administration of nutrients bypassing the gastrointestinal tract to support patients with impaired enteral absorption.

Intestinal failure–associated liver disease (IFALD): A spectrum of liver injuries, including cholestasis and steatosis, arising from prolonged PN.

Cholestasis: Impaired bile flow leading to accumulation of bile acids and bilirubin in the liver and circulation.

Lipid emulsion: Intravenous fat particles providing essential fatty acids and caloric support within PN solutions.

NF-κB signalling: A cellular pathway activated by inflammatory cytokines that can suppress transcription of bile transporter genes.

Farnesoid X receptor (FXR): A nuclear receptor regulating bile acid synthesis, transport and hepatic lipid metabolism.

References

1. Natural bioactive compounds–The promising candidates for the treatment of intestinal failure-associated liver disease. Clinical Nutrition (2024).
2. Investigation of parenteral nutrition-induced hepatotoxicity using human liver spheroid co-cultures. Archives of Toxicology (2024).
3. n-3 Polyunsaturated Fatty Acid Supplementation Affects Oxidative Stress Marker Levels in Patients with Type II Intestinal Failure: A Randomized Double Blind Trial. Antioxidants (2023).
4. Macrophage-derived IL-1β/NF-κB signaling mediates parenteral nutrition-associated cholestasis. Nature Communications (2018).
5. Stat3 role in the protective effect of FXR Agonist in parenteral nutrition-associated cholestasis. Hepatology Communications (2023).