Tuesday, February 20, 2007
Review article: bacterial flora and pathogenesis in hepatic encephalopathy
Review article: bacterial flora and pathogenesis in hepatic encephalopathy
Aliment Pharmacol Ther. 2007 Feb
Williams R.
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]
RELATED:
Review article: the current pharmacological therapies for hepatic encephalopathy.
Aliment Pharmacol Ther. 2007 Feb
Bass NM.
University of California, San Francisco, CA, USA.
Effective treatment options for hepatic encephalopathy are limited. Based on the principle that intestinal-derived ammonia contributes to the pathogenesis of hepatic encephalopathy, current therapeutic approaches are directed at reducing bacterial production of ammonia and enhancing its elimination. Non-absorbable disaccharides are first-line therapy for hepatic encephalopathy, but published clinical studies evaluating their safety and efficacy are limited. Alternative therapies such as benzodiazepine receptor antagonists, branched-chain amino acids, and l-ornithine-l-aspartate also have limited clinical data supporting their use. Studies of antibiotics indicate that they are effective in the treatment of hepatic encephalopathy, but adverse effects and concerns about long-term safety have limited the widespread use of most. Rifaximin is a minimally absorbed antibiotic that concentrates in the gastrointestinal tract and is excreted mostly unchanged in faeces. It has been studied extensively in the treatment of hepatic encephalopathy and appears to confer therapeutic benefits greater than those of placebo and non-absorbable disaccharides and at least comparable with those of systemic antibiotics. Rifaximin was also well tolerated in patients with hepatic encephalopathy and is not associated with clinical drug interactions or clinically relevant bacterial antibiotic resistance. In conclusion, non-absorbed antibiotics such as rifaximin offer a favourable benefit-risk ratio in the treatment of hepatic encephalopathy and may help to improve patient outcomes.
PMID: 17295849 [PubMed - in process]
Aliment Pharmacol Ther. 2007 Feb
Williams R.
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]
RELATED:
Review article: the current pharmacological therapies for hepatic encephalopathy.
Aliment Pharmacol Ther. 2007 Feb
Bass NM.
University of California, San Francisco, CA, USA.
Effective treatment options for hepatic encephalopathy are limited. Based on the principle that intestinal-derived ammonia contributes to the pathogenesis of hepatic encephalopathy, current therapeutic approaches are directed at reducing bacterial production of ammonia and enhancing its elimination. Non-absorbable disaccharides are first-line therapy for hepatic encephalopathy, but published clinical studies evaluating their safety and efficacy are limited. Alternative therapies such as benzodiazepine receptor antagonists, branched-chain amino acids, and l-ornithine-l-aspartate also have limited clinical data supporting their use. Studies of antibiotics indicate that they are effective in the treatment of hepatic encephalopathy, but adverse effects and concerns about long-term safety have limited the widespread use of most. Rifaximin is a minimally absorbed antibiotic that concentrates in the gastrointestinal tract and is excreted mostly unchanged in faeces. It has been studied extensively in the treatment of hepatic encephalopathy and appears to confer therapeutic benefits greater than those of placebo and non-absorbable disaccharides and at least comparable with those of systemic antibiotics. Rifaximin was also well tolerated in patients with hepatic encephalopathy and is not associated with clinical drug interactions or clinically relevant bacterial antibiotic resistance. In conclusion, non-absorbed antibiotics such as rifaximin offer a favourable benefit-risk ratio in the treatment of hepatic encephalopathy and may help to improve patient outcomes.
PMID: 17295849 [PubMed - in process]
Labels: bacterial flora, Hepatic encephalopathy, Non-absorbable disaccharides, pharmacological therapies, Rifaximin
# posted by Pat O'Connor @ 5:15 AM 
