Management of hepatic encephalopathy in patients with cirrhosis (original) (raw)

Pathogenesis, diagnosis, and treatment of hepatic encephalopathy

Journal of clinical and experimental hepatology, 2011

Hepatic encephalopathy (HE) is a neuropsychiatric disorder seen in patients with advanced liver disease or porto-systemic shunts. Based on etiology and severity of HE, the World Congress of Gastroenterology has divided HE into categories and sub-categories. Many user-friendly computer-based neuropsychiatric tests are being validated for diagnosing covert HE. Currently, emphasis is being given to view HE deficits as a continuous spectrum rather than distinct stages. Ammonia is believed to play crucial role in pathogenesis of HE via astrocyte swelling and cerebral edema. However, evidence has been building up which supports the synergistic role of oxidative stress, inflammation and neurosteroids in pathogenesis of HE. At present, treatment of HE aims at decreasing the production and intestinal absorption of ammonia. But as the role of new pathogenetic mechanisms becomes clear, many potential new treatment strategies may become available for clinician.

Hepatic Encephalopathy: Diagnosis and Current Therapies

2015

Hepatic encephalopathy (HE) is a neuropsychological, and a serious neurotoxic disease. HE varies in clinical presentation, in pathogenesis and treatment. HE is caused by the accumulation in the bloodstream of toxic substances that are normally removed by the liver.Clinical manifestations of HE include a wide spectrum of neuropsychiatric and neurological symptoms, disorientation and poor coordination. Acute HE is associated with severe liver failure in patients with fulminant hepatic failure. In chronic HE have neuropsychiatric syndrome characterized with depression of the central nervous system, with varying degrees of severity. HE is traditionally graded into four clinical stages. The synergistic effects of excess ammonia and inflammation cause astrocyte swelling and cerebral edema. Diagnosis of HE include neuropsychometric tests, brain imaging and clinical scales, the West Haven Criteria. Treatment is based on reducing the production and absorption of ammonia, with anti-microbial ...

Current concepts in the assessment and treatment of Hepatic Encephalopathy

QJM: An International Journal of Medicine, 2009

Hepatic encephalopathy (HE) is defined as a metabolically induced, potentially reversible, functional disturbance of the brain that may occur in acute or chronic liver disease. Standardized nomenclature has been proposed but a standardized approach to the treatment, particularly of persistent, episodic and recurrent encephalopathy associated with liver cirrhosis has not been proposed. This review focuses on the pathogenesis and treatment of HE in patients with cirrhosis. The pathogenesis and treatment of hepatic encephalopathy in fulminant hepatic failure is quite different and is reviewed elsewhere.

Hepatic encephalopathy: An approach to its multiple pathophysiological features

World Journal of Hepatology, 2012

Hepatic encephalopathy (HE) is a neuropsychiatric complex syndrome, ranging from subtle behavioral abnormalities to deep coma and death. Hepatic encephalopathy emerges as the major complication of acute or chronic liver failure. Multiplicity of factors are involved in its pathophysiology, such as central and neuromuscular neurotransmission disorder, alterations in sleep patterns and cognition, changes in energy metabolism leading to cell injury, an oxidative/nitrosative state and a neuroinflammatory condition. Moreover, in acute HE, a condition of imminent threat of death is present due to a deleterious astrocyte swelling. In chronic HE, changes in calcium signaling, mitochondrial membrane potential and long term potential expression, N-methyl-D-aspartate-cGMP and peripheral benzodiazepine receptors alterations, and changes in the mRNA and protein expression and redistribution in the cerebral blood flow can be observed. The main molecule indicated as responsible for all these changes in HE is ammonia. There is no doubt that ammonia, a neurotoxic molecule, triggers or at least facilitates most of these changes. Ammonia plasma levels are increased two-to three-fold in patients with mild to moderate cirrhotic HE and up to ten-fold in patients with acute liver failure. Hepatic and inter-organ trafficking of ammonia and its metabolite, glutamine (GLN), lead to hyperammonemic conditions. Removal of hepatic ammonia is a differentiated work that includes the hepatocyte, through the urea cycle, converting ammonia into GLN via glutamine synthetase. Under pathological conditions, such as liver damage or liver blood by-pass, the ammonia plasma level starts to rise and the risk of HE developing is high. Knowledge of the pathophysiology of HE is rapidly ex-HE is rapidly ex-HE is rapidly expanding and identification of focally localized triggers has led the development of new possibilities for HE to be considered. This editorial will focus on issues where, to the best of our knowledge, more research is needed in order to clarify, at least partially, controversial topics.

Management of Hepatic Encephalopathy

International Journal of Hepatology, 2011

Hepatic encephalopathy (HE), the neuropsychiatric presentation of liver disease, is associated with high morbidity and mortality. Reduction of plasma ammonia remains the central therapeutic strategy, but there is a need for newer novel therapies. We discuss current evidence supporting the use of interventions for both the general management of chronic HE and that necessary for more acute and advanced disease.

Current Management of Hepatic Encephalopathy: A Review Article

Journal for Research in Applied Sciences and Biotechnology

Hepatic encephalopathy, a neuropsychiatric syndrome stemming from liver failure, manifests in acute and chronic cases. The prevailing cause behind its development involves the neurotoxicity resulting from elevated ammonia levels in the brain, which can occur due to increased ammonia production or impaired ammonia excretion. The main objective in treating hepatic encephalopathy is to decrease ammonia levels. The detoxification of ammonia in this condition is regulated by two enzymes: glutaminase and glutamine synthetase. Numerous drugs, such as lactulose, rifaximin, BCAA, LOLA, glycerol phenylbutyrate, and zinc, have been utilized to treat hepatic encephalopathy. In terms of future research, experimental treatment options like fecal microbiota transplant, probiotics, bromocriptine, minocycline, indomethacin, ibuprofen, and flumazenil warrant investigation. Furthermore, albumin infusions have been shown to enhance cognitive function and improve the psychosocial quality of life, possib...

Hepatic Encephalopathy: An Update of Pathophysiologic Mechanisms

Proceedings of the Society for Experimental Biology and Medicine, 1999

Hepatic encephalopathy (HE) is a neuropsychiatric disorder that occurs in both acute and chronic liver failure. Although the precise pathophysiologic mechanisms responsible for HE are not completely understood, a deficit in neurotransmission rather than a primary deficit in cerebral energy metabolism appears to be involved. The neural cell most vulnerable to liver failure is the astrocyte. In acute liver failure, the astrocyte undergoes swelling resulting in increased intracranial pressure; in chronic liver failure, the astrocyte undergoes characteristic changes known as Alzheimer type II astrocytosis. In portal-systemic encephalopathy resulting from chronic liver failure, astrocytes manifest altered expression of several key proteins and enzymes including monoamine oxidase B, glutamine synthetase, and the socalled peripheral-type benzodiazepine receptors. In addition, expression of some neuroneal proteins such as monoamine oxidase A and neuronal nitric oxide synthase are modified. In acute liver failure, expression of the astrocytic glutamate transporter GLT-1 is reduced, leading to increased extracellular concentrations of glutamate. Many of these changes have been attributed to a toxic effect of ammonia and/or manganese, two substances that are normally removed by the hepatobiliary route and that in liver failure accumulate in the brain. Manganese deposition in the globus pallidus in chronic liver failure results in signal hyperintensity on T1-weighted Magnetic Resonance Imaging and may be responsible for the extrapyramidal symptoms characteristic of portal-systemic encephalopathy. Other neurotransmitter systems implicated in the pathogenesis of hepatic encephalopathy include the serotonin system, where a synaptic deficit has been suggested, as well as the catecholaminergic and opioid systems. Further elucidation of the precise nature of these alterations could result in the design of novel pharmacotherapies for the prevention and treatment of hepatic encephalopathy.

Mechanisms, diagnosis and management of hepatic encephalopathy

Nature Reviews Gastroenterology & Hepatology, 2010

| Hepatic encephalopathy (HE) is a serious neuropsychiatric complication of both acute and chronic liver disease. Symptoms of HE can include confusion, disorientation and poor coordination. A general consensus exists that the synergistic effects of excess ammonia and inflammation cause astrocyte swelling and cerebral edema; however, the precise molecular mechanisms that lead to these morphological changes in the brain are unclear. Cerebral edema occurs to some degree in all patients with HE, regardless of its grade, and could underlie the pathogenesis of this disorder. The different grades of HE can be diagnosed by a number of investigations, including neuropsychometric tests (such as the psychometric hepatic encephalopathy score), brain imaging and clinical scales (such as the West Haven criteria). HE is best managed by excluding other possible causes of encephalopathy alongside identifying and the precipitating cause, and confirming the diagnosis by a positive response to empiric treatment. Empiric therapy for HE is largely based on the principle of reducing the production and absorption of ammonia in the gut through administration of pharmacological agents such as rifaximin and lactulose, which are approved by the FDA for the treatment of HE.