4 The development of overt hepatic encephalopathy is itself

a poor prognostic indicator.5,6 Gastrointestinal bleeding, in particular, an acute variceal bleed, is a common precipitant of hepatic encephalopathy. The exact prognostic significance of hepatic encephalopathy in the context of an acute variceal bleed is unclear; however, following a first episode, the overall transplant-free survival at 1 year is only 42%.6 The pathogenesis of hepatic encephalopathy is complex and imprecisely defined. It is thought to revolve around elevated levels of ammonia, an inflammatory response, click here and subsequent astrocyte swelling leading to cerebral edema.5 The neuropsychiatric disorder that results is variable, and is by consensus clinically defined using the West Haven criteria developed by Conn et al. in 1977.7,8 Ammonia is produced as a byproduct of the metabolism of nitrogen-containing compounds, abundant in the bacterial flora of the gastrointestinal tract. In the “normal” system, the liver removes systemic ammonia by converting it to the water soluble urea. In liver disease, however, this function is impaired (due to either hepatocellular failure or portosystemic shunting) and brain and muscle Selleck Pirfenidone cells are increasingly involved, converting ammonia to glutamine.5,9 The treatment of hepatic encephalopathy has thus focused around reducing the production and absorption of ammonia in the gut.5 Precipitants of hepatic

encephalopathy are many. In the case of an acute

gastrointestinal bleed, increased ammonia levels arise from the high protein load in the gut. The Baveno IV guidelines, and subsequent AASLD (American Association for the Study of Liver Diseases) practice guidelines, for the management of portal hypertension, outline key management issues immediately after an acute bleeding episode, including the recommendation for antibiotic prophylaxis GPCR & G Protein inhibitor for preventing bacterial infections/spontaneous bacterial peritonitis.10,11 Furthermore, there is a recommendation that treatment with lactulose is indicated if hepatic encephalopathy eventuates.10,11 However, while it would seem prudent to use lactulose as prophylaxis in a setting that is well known to precipitate the condition, this is not currently a guideline recommendation. Lactulose, a non-absorbable disaccharide, is not degraded in the upper gastrointestinal tract. Aside from its cathartic effect, lactulose reduces the synthesis and absorption of ammonia by driving the conversion of ammonia to the non-absorbable ammonium via a reduction in the colonic pH.5,12 A Cochrane Review in 2004 of studies from 1969 to 2003 evaluated the beneficial effect of lactulose in hepatic encephalopathy, and concluded that the evidence was insufficiently sound to support its use. Furthermore, the authors recommended that it should not be utilized as a comparator in future trials.3 However, a study published in 2009 by Sharma et al.