Valérie McLin, Professor in the Department of Paediatrics, Gynaecology and Obstetrics at the UNIGE Faculty of Medicine and Head of the Paediatric Gastroenterology, Hepatology and Nutrition Unit at HUG, will coordinate with Cristina Cudalbu and Bernard Lanz from EPFL and CITB an important research project on chronic hepatic encephalopathy in children, a serious neurological complication linked to chronic liver diseases. This project, worth nearly 3 million francs, is funded by the SNSF.

Chronic hepatic encephalopathy (CHE) is a serious neurological complication linked to chronic liver diseases. Particularly difficult to diagnose in children, it can lead to severe long-term neurological sequelae. "CHE is associated with an accumulation of glutamine in the brain, a particularly dangerous mechanism in the developing brain as it alters its structure and reduces available energy," explains Valérie McLin. "However, it remains unclear how this Gln accumulation modifies brain cells and contributes to cognitive disorders."

Imaging, 3D models and studies with patients

The research team's hypothesis is that an early increase in Gln reduces the complexity of neural networks and disrupts energy metabolism. Their objective is therefore to study the impact of glutamine on brain structure and energy through an innovative approach combining metabolic and diffusion imaging (MRI, magnetic resonance spectroscopy, PET). The project combines 3D brain organoids, animal models and children with congenital portosystemic shunts or chronic liver diseases.

This project is the result of a long-standing collaboration between the teams of Cristina Cudalbu and Valérie McLin. This collaboration now continues with a focus on juvenile models, including Bernard Lanz to study the effects of Gln on brain microstructure in animal and organoid models, analyse the impact of Gln on cerebral energy metabolism, and study brain changes in children before and after closure of congenital portosystemic shunts, Valérie McLin's area of expertise in paediatric hepatology and its links with neurocognitive disorders in children with hepatic bypass or chronic liver disease.

Unique expertise

"The shunt model is unique as it allows us to study the effect of hepatic bypass in isolation, without the background noise of liver disease. This is why the potential scope of this study is considerable. Its potential benefits extend beyond the brain development of children with liver disease: Its relevance may extend to millions of patients with cirrhosis and liver disease," concludes Valérie McLin.