When a diseased liver disrupts the brain: Health & Medicine: Nature World News

August 19, 2019 12:09 pm EDT

The liver plays a vital role as a filter in the human body. But what happens when it works badly? Researchers from the Universities of Geneva (UNIGE) and Lausanne (UNIL), the Vaud University Hospital Center (CHUV), the Center for Biomedical Imaging (CIBM), the Swiss Federal Institute of Technology Lausanne (EPFL) and Geneva University Hospitals (HUG), Switzerland, have teamed up to conduct a detailed badysis of hepatic encephalopathy, a type of brain injury caused by chronic liver disease.

Scientists were able to observe for the first time, on a mouse model, that a liver dysfunction causes cerebral molecular disturbances in two weeks, although no physical symptoms are apparent. In addition, several molecules are involved, two previously unknown. The results of the research, which you can read in the Journal of Hepatology, could help detect brain damage related to liver disease via brain badysis before an individual's health status worsens .

When the liver is sick, as is the case with cirrhosis, a number of substances are no longer filtered, which can cause psychological, motor and neurocognitive disorders in the adult. This disease, called hepatic encephalopathy, can manifest itself in a wide spectrum of symptoms, even in coma. Ammonium is one of the players in hepatic encephalopathy.

As Valérie McLin, professor in the Department of Pediatrics, Gynecology and Obstetrics at the UNIGE School of Medicine and Geneva University Hospitals (HUG) explains, "Ammonium is a substance produced when proteins break down, some of which are directed to the brain. " is transformed into glutamine – used for the production of neurotransmitters – while the other part is filtered by the liver and excreted in the urine. "However, in case of liver dysfunction, it causes an excessive amount of ammonium in the brain and therefore a production of glutamine, which can cause cerebral edema and, in some cases, hepatic encephalopathy." Two unknowns remain : are there other molecular players responsible for hepatic encephalopathy? How long does it take for the brain to be affected by liver dysfunction?

Impact much earlier than expected

In an attempt to answer these questions, researchers observed rats with chronic liver disease for eight weeks. "Each animal was individually monitored by high magnetic field MRI (9.4 Tesla) every two weeks for high-resolution spectroscopy (MRS), allowing us to observe molecular alterations very accurately. from the beginning of a liver disease, "said Dr. Cristina Cudalbu, research scientist and operational director of the Center for Biomedical Imaging of MRI 9.4T, at EPFL. "And we have discovered unpublished observations!"

Scientists have discovered that molecular changes affect the brain as early as the second week of liver disease. And yet, rats have minimal symptoms of the disease. "Based on previous studies, we thought it would take about six weeks to see an impact, that is, at the beginning of the deterioration of the animal's health." "says Dr. Cudalbu.

The external signs of the disease appear between the fourth and the eighth week: jaundice, malnutrition or water in the belly. "From that moment, we observed that in addition to the excess of ammonium in the brain, the concentration of the other two molecules was falling: vitamin C, an antioxidant, and creatine, which fulfills many functions, including functions related to energy, "says Olivier Braissant, professor in the department of clinical chemistry of the CHUV and the faculty of biology and medicine of the University of Lausanne (UNIL ).

This is the first time that the role played by these two new players in the disease is clearly demonstrated. "These appear in a second phase after the rise of ammonium in the blood," says Professor Braissant.

Should the brain be badyzed for liver disease?

The results suggest that an MRS brain scan could detect the neurological manifestations of chronic liver disease well before the onset of the first symptoms. But the researchers also aim to find out if it would be possible to protect the brain from this type of deterioration – or at least to reduce the damage – by compensating for the lack of creatine and vitamin C through supplements or probiotics. "We are also doing similar observations in humans to determine if the brain lesions are similar to those in the rat," concludes Professor McLin.