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Traditional views of the pathogenesis of hepatic encephalopathy (HE) have emphasised the role of neurotoxins arising from the gut. These compounds gain access to the systemic circulation as a result of the combined effects of hepatocellular failure and portal-systemic shunting. In the past years, a new mechanistic paradigm has been developed, emphasising changes in brain astrocyte function with subsequent alterations in glial-neuronal communications.1 ,2 Astrocyte dysfunction results from several factors. These include a decrease in plasma osmolarity, effects of circulating cytokines, and the changes brought on by accumulation of glutamine, the product of ammonia detoxification in glial cells. After many years of research, ammonia continues to play a central role in the pathogenesis of HE.
Under normal conditions, ammonia is generated in both the small bowel (from the effects of glutaminase on glutamine) and large intestine (from the urease activity of the colonic flora). The relative contribution of each site is difficult to quantitate but hyperammonaemic coma can still occur in hepatectomised germ free rats3 where the main source of ammonia is presumably the small bowel. Neomycin, an antibiotic active against urease containing bacteria in the colon, also …