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.