# Dysregulation of Trace Elements in Pediatric Cholestasis: From Pathophysiology to Nutritional Approaches

## TL;DR

This review explores how imbalances in trace elements like zinc and copper affect children with cholestasis and suggests tailored nutritional strategies for better outcomes.

## Contribution

The paper provides a comprehensive overview of trace element dysregulation in pediatric cholestasis and highlights precision nutritional approaches.

## Key findings

- Zinc and selenium deficiencies are common in pediatric cholestasis, leading to growth and immune issues.
- Copper and manganese accumulation due to reduced biliary excretion can worsen liver injury and cause neurotoxicity.
- Understanding metal-specific transporters offers new insights into managing trace element imbalances in cholestatic disease.

## Abstract

Cholestasis in children is characterized by impaired bile flow that disrupts hepatic metabolism, nutrient homeostasis, and effects trace element balance. This narrative review summarizes current evidence on the metabolism, biological functions, and clinical implications of key trace elements—zinc, selenium, copper, and manganese—in pediatric cholestatic liver disease. The liver regulates trace element absorption, intracellular trafficking, storage, and biliary excretion; cholestasis alters these processes, leading to deficiencies or toxic accumulation. Zinc and selenium deficiencies are common and contribute to impaired growth, immune dysfunction, oxidative stress, and delayed hepatic regeneration. Conversely, reduced biliary excretion promotes copper and manganese accumulation, potentially exacerbating liver injury and causing manganese-related neurotoxicity. Recent advances in understanding metal-specific hepatic transporters and trafficking pathways have provided mechanistic insight into these alterations. Management strategies emphasize individualized supplementation, monitoring during enteral and parenteral nutrition, and prevention of deficiency and toxicity. Precision-based nutritional approaches may improve outcomes in pediatric cholestatic liver disease.