Review article: bacterial flora and pathogenesis in hepatic encephalopathy

Abstract

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.