Hepatic encephalopathy: A review (original) (raw)

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.

Management of hepatic encephalopathy in patients with cirrhosis

Best Practice & Research Clinical Gastroenterology, 2007

The term hepatic encephalopathy encompasses a spectrum of neuropsychiatric abnormalities seen in patients with liver dysfunction. Distinct syndromes are identified in acute liver failure and cirrhosis. Rapid deterioration in consciousness level and increased intracranial pressure that may result in brain herniation and death are a feature of acute liver failure whereas manifestations of hepatic encephalopathy in cirrhosis include psychomotor dysfunction, impaired memory, increased reaction time, sensory abnormalities, poor concentration and in severe forms, coma. In patients with acute-on-chronic liver failure the pathophysiology remains undefined. Ammonia has been considered central to its pathogenesis. In the brain, the astrocyte is the main site for ammonia detoxification, during the conversion of glutamate to glutamine. An increased ammonia level raises the amount of glutamine within astrocytes, causing an osmotic imbalance resulting in cell swelling and ultimately brain oedema. Recent studies suggest that inflammation and it modulators may play a synergistic role with ammonia in the pathogenesis of hepatic encephalopathy. Therapy of hepatic encephalopathy is directed primarily at reducing ammonia generation and increasing its detoxification. The currently accepted regimens to treat hepatic encephalopathy such as lactulose and protein restricted diets need further clinical trials and therefore placebo controlled clinical trials in hepatic encephalopathy are justified. In liver failure, ammonia metabolism involves multiple organs and therefore ammonia reduction will require simultaneous targeting of these organs. The present review describes the pathophysiological basis of hepatic encephalopathy and evaluates the available therapies.

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: a critical current review

Hepatology international, 2018

Hepatic encephalopathy (HE) is a serious neuropsychiatric complication of cirrhosis and/or porto-systemic shunting. The clinical symptoms are widely variable, extending from subtle impairment in mental state to coma. The utility of categorizing the severity of HE accurately and efficiently serves not only to provide practical functional information about the current clinical status of the patient but also gives valuable prognostic information. In the past 20-30 years, there has been rapid progress in understanding the pathophysiological basis of HE; however, the lack of direct correlation between pathogenic factors and the severity of HE make it difficult to select appropriate therapy for HE patients. In this review, we will discuss the classification system and its limitations, the neuropsychometric assessments and their challenges, as well as the present knowledge on the pathophysiological mechanisms. Despite the many prevalent hypotheses around the pathogenesis of the disease, mo...

Hepatic Encephalopathy: An Update of Pathophysiologic Mechanisms (44433A)

2000

Hepatic encephalopathy (HE) is a neuropsychiatric disorder that occurs in both acute and chronic liver failure. Although the precise pathophysiologic mecha- nisms responsible for HE are not completely understood, a deficit in neurotransmis- sion rather than a primary deficit in cerebral energy metabolism appears to be in- volved. The neural cell most vulnerable to liver failure is the astrocyte. In

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.

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 ...

Pathophysiological changes associated with increasing grade of hepatic encephalopathy

Journal of the National Medical Association, 1988

The pathophysiological changes occurring with increasing grade of encephalopathy were examined in 93 consecutive episodes in 44 patients with liver cirrhosis (37 posthepatic). The incidence of gastrointestinal bleeding and leukocytosis increased significantly when the grade advanced from 1 to 5. The following variables showed a trend for change that did not reach statistical significance: rising serum bilirubin, SGOT, and BUN levels; decreasing serum sodium and chloride levels; and increased incidence of infection. The mean values of the following variables were significantly different in 25 fatal episodes and 68 survivors, implicating a bad prognosis: high serum bilirubin, alkaline phosphatase, and BUN levels; low serum albumin, sodium, and chloride levels; and a higher incidence of severe infections (sepsis, infected ascitic fluid). Because increasing grade of encephalopathy is the most important factor in determining the prognosis of hepatic encephalopathy (mortality 0, 10, 5, 19...

Hepatic Encephalopathy: An Overview of Basic Concepts and Mechanisms

Frontiers in Medical Case Reports

The liver failure induced encephalopathy is commonly referred as hepatic encephalopathy (HE). For many decades, scientists have tried to describe the symptoms of this disorder revealing a spectrum with different types of HE. Studies on the mechanisms underlying the pathogenesis of HE have implicated several factors, mainly neurotoxins, including ammonia, manganese, in addition to changes in various physiological factors, especially an imbalance between true and false neurotransmitters, as well as the involvement of various pro-inflammatory mediators. Such changes impact on the brain, which promote disorders in glia and neurons. This review focuses on the most relevant basic pathophysiologic mechanisms associated with HE.