Gastroenterology

The researches find that the chronic liver diseases cause molecular changes in the brain. They carried out their research using the 9.4 Tesla high-magnetic-field MRI machine at the Center for Biomedical Imaging (CIBM) at EPFL. The liver plays a vital role as a filter in the human body. But what happens when it malfunctions? A physicist from EPFL; a clinician from the University of Geneva (UNIGE); and the Geneva University Hospitals (HUG) and a biologist from the Vaud University Hospital Centre (CHUV) and the Universities of Lausanne (UNIL); teamed up to perform a detailed analysis of hepatic encephalopathy; a type of brain damage caused by chronic liver disease.

Chronic liver diseases

For the first time; the scientists observed how diseased mouse livers can cause molecular disturbances in the animals’ brains within two weeks, before any physical symptoms appear. They also discovered the previously unknown role of two particular molecules in the process. Therefore Their findings; published in the Journal of Hepatology; suggest that brain scans could help detect liver-related brain damage in humans before their health visibly deteriorates.

The livers of adults suffering from a liver disease like cirrhosis no longer filter out numerous substances. The psychological, motor and neurocognitive disorders that may result; referred to as hepatic encephalopathy, present a wide range of symptoms, including coma. One substance known to play a role in hepatic encephalopathy is ammonium.

Motor and neurocognitive disorders

“Ammonium is produce when proteins break down,” says Valérie McLin, a professor in the Department of Pediatrics; Gynecology and Obstetrics at UNIGE’s Faculty of Medicine and HUG. But “Some of the ammonium goes to the brain, where it is transform into glutamine and used to produce neurotransmitters. The rest is filtered by the liver and excrete in urine. When the liver malfunctions, too much ammonium goes to the brain.

The resulting rise in glutamine production can trigger cerebral edema and, in some cases, hepatic encephalopathy.” That much is known, yet two key questions remained: Are any other molecules involved in hepatic encephalopathy? And how long does it take for a diseased liver to affect the brain? In order to answer these questions, the researchers observed mice with chronic liver disease for eight weeks. Because “They monitored the animals individually,” says Cristina Cudalbu, a research physicist who manages the 9.4 Tesla MRI machine at the CIBM at EPFL.

“Every two weeks, we analyzed them through high-resolution spectroscopy by placing them in a 9.4 Tesla high-magnetic-field MRI machine. Therefore This allowed us to track the molecular changes in their brains very precisely from the very onset of the liver disease. And we made some important discoveries!”