Reduced cortical thickness in patients with acute-on-chronic liver failure due to non-alcoholic etiology

Background: Acute-on-chronic liver failure (ACLF) is a form of liver disease with high short-term mortality. ACLF offers considerable potential to affect the cortical areas by significant tissue injury due to loss of neurons and other supporting cells. We measured changes in cortical thickness and metabolites profile in ACLF patients following treatment, and compared it with those of age matched healthy volunteers. Methods: For the cortical thickness analysis we performed whole brain high resolution T1-weighted magnetic resonance imaging (MRI) on 15 ACLF and 10 healthy volunteers at 3T clinical MR scanner. Proton MR Spectroscopy (1H MRS) was also performed to measure level of altered metabolites. Out of 15 ACLF patients 10 survived and underwent follow-up study after clinical recovery at 3 weeks. FreeSurfer program was used to quantify cortical thickness and LC- Model software was used to quantify absolute metabolites concentrations. Neuropsychological (NP) test was performed to assess the cognitive performance in follow-up ACLF patients compared to controls. Results: Significantly reduced cortical thicknesses in multiple brain sites, and significantly decreased N-acetyl aspartate (NAA), myo-inositol (mI) and significantly increased glutamate/glutamine (glx) metabolites were observed in ACLF compared to those of controls at baseline study. Follow-up patients showed significant recovery in cortical thickness and Glx level, while NAA and mI were partially recovered compared to baseline study. When compared to controls, follow-up patients still showed reduced cortical thickness and altered metabolites level. Follow-up patients had abnormal neuropsychological (NP) scores compared to controls. Conclusions: Neuronal loss as suggested by the reduced NAA, decreased cellular density due to increased cerebral hyperammonemia as supported by the increased glx level, and increased proinflammatory cytokines and free radicals may account for the reduced cortical thickness in ACLF patients. Presence of reduced cortical thickness, altered metabolites and abnormal NP test scores in post recovery subjects as compared to those of controls is associated with incomplete clinical recovery. The current imaging protocol can be easily implemented in clinical settings to evaluate and monitor brain tissue changes in patients with ACLF during the course of treatment

METABOLISM AND BRAIN UPTAKE OF GAMMA-AMINOBUTYRIC ACID IN GALACTOSAMINE-INDUCED HEPATIC-ENCEPHALOPATHY IN RATS

Kinetic studies of [3H]\u3b3-aminobutyric acid ([3H]GABA) after an intravenous injection were performed in normal rats and in rats with severe degree of hepatic encephalopathy due to fulminant hepatic failure induced by galactosamine. Moreover, plasma and brain GABA levels, and GABA and glutamic acid decarboxylase activity were studied in some brain areas. After intravenous injection, [3H]GABA disappeared very rapidly in the blood of normal rats, with a prompt increase of 3H metabolites. In comatose rats, a delayed disappearance of [3H]GABA was paralleled by a lower amount of metabolites, indirectly indicating a peripheral decrease of GABA-transaminase activity. The amount of [3H]GABA in brain was lightly but constantly lower in comatose rats than in controls, indicating that the change in permeability of the blood-brain barrier in hepatic encephalopathy does not affect the [3H]GABA uptake of the brain. Furthermore, the assay of endogenous GABA in blood, whole brain, and brain areas did not show any significant difference in any of the two groups. The findings that glutamic acid decarboxylase activity in brain was reduced, together with the indirect evidence of a reduction in GABA-transaminase, may account for the steady state of GABA in hepatic encephalopathy. However, the reduction in glutamic acid decarboxylase activity is in favor of a functional derangement at the GABA-ergic nerve terminals in this pathological condition

Presence of benzodiazepine-like compound molecules in food and their implication in the nutrition of cirrhotic patients

Benzodiazepine (BDZ)-like compounds, present in trace amounts in normal subjects increase in the blood of liver cirrhotic patients. The origin of these compounds is still unknown but they are present in medicinal plants and foods. Herein we report the detection of BDZ-like molecules in fruits, vegetables, cereals, meat, milk and cheeses and in different cultivars of potatoes, tomatoes and carrots. The extracted food was separated by HPLC purification and the collected fractions were tested by radioreceptor binding assay in order to evaluate their ability to selectively bind the central benzodiazepine receptors. The mean value was 14.80 ng of diazepam equivalent (DE)/g in fruits, 4.34 ng DE/g in vegetables, 6.35 in cereals and 4.09 in meat. BDZ-like compounds are poorly present in cheeses and completely absent in olive and seeds oil. From these findings it is possible to select food with low amount of BDZ-like molecules useful for cirrhotic diet in order to prevent hepatic encephalopathy

Decrease of brain zinc in experimental hepatic encephalopathy

Since zinc is an important factor in membrane stability, we assayed the levels of zinc in several brain areas during the development of hepatic encephalopathy due to d-galactosamine-HC1 in rat. We now report that zinc is significantly reduced in all tested brain areas. This finding seems to indicate an involvement of zinc in the changes of membrane properties that lead to alteration of GABA receptors in hepatic encephalopathy. © 1983