Wednesday, February 14, 2007
Review article: bacterial flora and pathogenesis in hepatic encephalopathy.
Aliment Pharmacol Ther. 2007 Feb;25
The UCL Institute of Hepatology, Royal Free and University College Medical School, University College London, UK.
The aetiology of hepatic encephalopathy has not been conclusively established, but it is widely agreed that ammonia derived primarily from enteric bacterial flora plays a central role. Recent research on the pathogenesis of hepatic encephalopathy reinforces previous findings, supporting an integral role of bacteria-derived ammonia and reveals other potential mechanisms by which bacterial flora and pathogens may be pathophysiologically important. This review discusses this research and considers its implications for the therapeutic management of hepatic encephalopathy. Besides producing ammonia, the enteric flora generates other neurotoxic products, such as phenols and mercaptans, that may potentiate the effects of ammonia. Bacteria may also constitute a primary source of the benzodiazepine-like compounds implicated in neuropsychiatric symptoms in patients with liver disease. New evidence suggests that acute bacterial infections, long recognized as important precipitants of hepatic encephalopathy, may mediate clinical worsening through effects on systemic inflammatory responses. Considered together, these data suggest wide-ranging pathophysiological contributions of bacteria to hepatic encephalopathy and underline the potential for an integral role of antibiotics and other bactericidal agents in its management.
PMID: 17295848 [PubMed - in process]
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Management of hepatic encephalopathy in patients with cirrhosis.
Best Pract Res Clin Gastroenterol. 2007
Liver Failure Group, The UCL Institute of Hepatology, Division of Medicine, University College London, 69-75 Chenies Mews, London WC1E 6HX, UK.
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.
Management of hepatic encephalopathy: role of rifaximin.
Department of Medicine and Medical Specialities, University of Modena and Reggio Emilia, Modena, Italy. email@example.com
Hepatic encephalopathy (HE) is a neuropsychiatric syndrome, which develops in patients with acute or chronic liver failure. It is widely accepted to be due to impairment of hepatic clearance of toxic products from the gut such as ammonia. Accumulation of ammonia induces a glutamate neurotoxicity leading to an increased tone of the gamma-aminobutyric acid A (GABA-A) receptor system in the brain which results in HE. Factors either increasing the ammonia levels (protein load, constipation, sepsis, or gastrointestinal bleeding) or potentiating the functional activity of the GABAergic system [natural benzodiazepine-like compounds (NBZDs) or exogenous benzodiazepines] may act as precipitating factors of HE. NBZDs are present in trace amounts in the blood of normal subjects and have been found to be increased in the blood of patients with liver cirrhosis, with or without HE. These compounds may derive either from the diet since they have been found in plants, vegetables and animals or from gut bacteria. The observation that intestinal bacterial flora is involved in the production of both primary agent of HE (ammonia) and precipitating factors (NBZDs) suggests that the use of nonabsorbable antibiotics such as rifaximin may be useful in preventing episodes of HE in patients with liver cirrhosis. Copyright (c) 2005 S. Karger AG, Basel.