Hepatic encephalopathy: current challenges and future prospects

Abstract

Hepatic encephalopathy (HE) is a common complication of liver dysfunction, including acute liver failure and liver cirrhosis. HE presents as a spectrum of neuropsychiatric symptoms ranging from subtle fluctuating cognitive impairment to coma. It is a significant contributor of morbidity in patients with liver disease. HE is observed in acute liver failure, liver bypass procedures, for example, shunt surgry and transjugular intrahepatic portosystemic shunt, and cirrhosis. These are classified as Type A, B and C HE, respectively. HE can also be classified according to whether its presence is overt or covert. The pathogenesis is linked with ammonia and glutamine production, and treatment is based on mechanisms to reduce the formation and/or removal of these compounds. There is no specific diagnostic test for HE, and diagnosis is based on clinical suspicion, excluding other causes and use of clinical tests that may support its diagnosis. Many tests are used in trials and experimentally, but have not yet gained universal acceptance. This review focuses on the definitions, pathogenesis and treatment of HE. Consideration will be given to existing treatment, including avoidance of precipitating factors and novel therapies such as prebiotics, probiotics, antibiotics, laxatives, branched-chain amino acids, shunt embolization and the importance of considering liver transplant in appropriate cases.

Sensitivity and Specificity of Alzheimer Type II Astrocytes in Hepatic Encephalopathy

“…In the glutamine synthetase-mediated reaction, ammonia and glutamate are converted to glutamine which, when in abundance, has the osmotic effect of cytoplasmic and then cerebral edema. [6][7][8] The type II astrocyte can be induced in laboratory animals when hepatic failure or bypass is induced, and astrocyte cultures, when exposed to excess ammonia, undergo enlargement and chromatin margination, taking on the morphologic features of type II astrocytes. 9 The appearance of type II astrocytes, therefore, is thought to be primarily the result of induction stimulated by the presence of ammonia.…”

“…3,4 Hyperammonemia results when, because blood bypasses the liver or passes through dysfunctional liver, ammonia is insufficiently converted to urea. [5][6][7][8] This is thought to be the cause of neurologic dysfunction in HE. Furthermore, experimental evidence demonstrates that the distinctive morphologic features of type II astrocytes can be induced by ammonia in vitro, and observational studies confirm that type II astrocytes are observed in animals and human patients with HE.…”

Role of the Gut–Liver Axis in Liver Inflammation, Fibrosis, and Cancer: A Special Focus on the Gut Microbiota Relationship

“…Hepatic encephalopathy (HE) is a serious complication of liver cirrhosis associated with neuropsychiatric impairment . HE is characterized by a high level of blood ammonia, which is known to be produced abundantly by gut microbiota expressing deaminating enzymes and/or urease operons and also by the host's organs, such as the liver and kidney . HE is caused by liver dysfunction, such as liver fibrosis, leading to impaired detoxication of ammonia and creation of portosystemic shunts, thereby facilitating the direct efflux of ammonia into the brain.…”

Characterization of Oxidative Stress and Ammonia According to the Different Grades of Hepatic Encephalopathy

“…Ammonia is the main metabolic alteration associated to HE after it crosses the blood-brain barrier [1]. Beyond the neurotransmitters in the pathogenesis of HE, the brain injury in cirrhosis is associated to inflammatory state and oxidative stress (OxS) induced by ammonia [2,3]. In astrocytes, neuronal and inducible nitric oxide synthases, NADPH oxidase, and mitochondria are sources of reactive nitrogen and oxygen species (RNOS) [4] that are neutralized by the endogenous antioxidants system.…”