Main description:

Hepatic Encephalopathy (HE) is a neuropsychiatric disorder resul t- ing from liver failure. HE may be associated with fulminant (acute) hepatic failure or chronic liver disease with portal-systemic shunting. The latter condition is characterized neuropathologically by astro- cytic rather than neuronal changes (Alzheimer Type II astrocytosis). The former is frequently accompanied by cerebral edema. Several hypotheses have been proposed to explain the pathogene- sis of HE. These include: 1. A toxic action of a substance (or substances) such as ammonia on brain function 2. A deficit of cerebral energy metabolism 3. Neurotransmitter changes, and, more recently 4. The role of "endogenous benzodiazepines. " This volume summarizes the results of a symposium held in Val David, Quebec from October 3D-November I, 1988, that was devoted to an evaluation of the evidence for and against the various hypothe- ses of HE. Data from studies in patients, in experimental (animal) models of HE, and in cultured cell preparations were discussed. In addition, a review of available approaches to the treatment and man- agement of HE was included.
The therapeutic use of lactulose, anti- biotics, dietary treatment, and branched-chain amino acid treatments were included, as well as the results of preliminary studies of the therapeutic use of the benzodiazepine antagonist, flumazenil. Roger F. Butterworth, PhD Gilles Pomier Layrargues, MD v Acknowledgments The symposium was made possible by the generous financial assistance of: Hoffman-La Roche Ltd.

Contents:

A. Introduction.- Hepatic Encephalopathy: The Present and the Future,.- B. Pathophysiology of Hepatic Encephalopathy.- The Role of Ammonia and Other Toxins.- Ammonia in Liver and Extrahepatic Tissues: An Overview of Metabolism and Toxicity in Mammals,.- Neurophysiology of Ammonia Intoxication,.- Effect of Portacaval Anastomosis on Ammonia Metabolism in Brain and Liver,.- Selective Inhibition of Mitochondrial Dehydrogenases by Ammonia and Fatty Acyl Coenzyme A Derivatives,.- Acute Action of Ammonia on Leucine Metabolism in Isolated Astrocytes, Neurons, and Oligo Cells of Rat Brain,.- Progressive Hyperammonemia and Insulin Resistance After Portacaval Shunt in Homozygous Familial Hypercholesterolemia,.- Mesenteric Venous Stenosis Reduces Hyperammonemia in the Portacaval Shunted Rat,.- Hyperammonemic Encephalopathy Syndrome Due to Urinary Bladder Distention and Infection.- Role of Toxins and Synergism in Hepatic Encephalopathy,.- Cerebral Metabolism and Function in Hepatic Failure.- Brain Energy Metabolism in Hepatic Encephalopathy.- In Vivo NMR Spectroscopy Studies of Cerebral Metabolism in Rats After Portacaval Shunting,.- Effects of Hypercarbia and Portacaval Shunting on Amino Acids and High Energy Phosphates of the Rat Brain: a 1H and 31P NMR Study,.- Positron-Emission Tomography in the Study of Hepatic Encephalopathy,.- The Use of Cultured Astrocytes in the Study of Hepatic Encephalopathy,.- Brain Edema in Experimental Fulminant Hepatic Failure,.- Encephalopathy of Reye's Syndrome: Studies of the Pathogenic Process in Animal Models,.- The Rat with Carbon Tetrachloride-Induced Cirrhosis as a Model of Hepatic Encephalopathy,.- GABA and Benzodiazepine Receptors in Hepatic Encephalopathy.- Hepatic Encephalopathy and Benzodiazepine Receptor Ligands,.- Detection and Characterization of Endogenous Benzodiazepine Activity in Both Animal Models and Humans with Hepatic Encephalopathy,.- Isolated CNS Neurons from a Model of Hepatic Encephalopathy Exhibit Increased Sensitivity to a Benzodiazepine,.- Studies of Central and "Peripheral-Type" Benzodiazepine Receptors in Autopsied Brain Tissue from Cirrhotic Patients with Hepatic Encephalopathy,.- Ro 15-1788 Kinetics are Markedly Impaired in Cirrhotic Patients,.- Plasma GABA-like Factor in Hepatic Encephalopathy May Be Taurine,.- Diazepam Metabolism in Perfused Cultures of Adult Rat Hepatocytes,.- Other Neurotransmitter Systems (amines, amino acids, peptides) in Hepatic Encephalopathy.- Hepatocerebral Dysfunction and Brain Serotonin,.- Biogenic Amines in Hepatic Encephalopathy: Evidence for Increased Serotonin Turnover in Human Brain,.- Increased Serotoninergic and Noradrenergic Activity in an Experimental Model of Hepatic Encephalopathy in Rats,.- Excitatory Amino Acids and Hepatic Encephalopathy,.- Activities of Glutamate-Related Enzymes in Autopsied Brain Tissue from Cirrhotic Patients with Hepatic Encephalopathy,.- Does Ammonia Exert its Neurotoxicity Through an Inhibition of Transmitter Glutamate Synthesis?.- Beta-Endorphin and Opiate Receptor Changes in Acute and Chronic Models of Hepatic Encephalopathy,.- C. Treatment of Hepatic Encephalopathy.- Update of Existing Therapeutic Approaches.- Treatment of Hepatic Encephalopathy. New Perspectives on Old Ideas,.- Treatment of Hepatic Encephalopathy with Lactulose and Antibiotics,.- Nutritional Therapy of Portal-Systemic Encephalopathy: The Branched-Chain Amino Acid Story,.- Nutrition, Diet, and Hepatic Encephalopathy,.- Partial Portal Decompression: Initial Clinical Experience with Small-Stoma Portacaval Shunt,.- Potential Therapeutic Use of Benzodiazepine Antagonists.- Benzodiazepine-Antagonist (Ro 15-1788) Flumazenil, Anexate (R), Pharmacokinetics, and Therapeutic Applications,.- Effects of the Benzodiazepine Antagonist Flumazenil in Hepatic Encephalopathy in Man,.- Treatment of Hepatic Encephalopathy with the Benzodiazepine Antagonist Flumazenil.