Review article: hyperammonaemic and catabolic consequences of upper gastrointestinal bleeding in cirrhosis S. W. M. OLDE DAMINK*,  , C. H. C. DEJONG* & R. JALAN à *Department of Surgery, Maastricht University Medical Centre and Nutrition & Toxicology Research Institute Maastricht (NUTRIM), Maastricht, The Netherlands;  Department of Surgery and àLiver Failure Group, Institute of Hepatology, University College London Medical School, London, UK Correspondence to: Dr S. W. M. Olde Damink, Department of Surgery, Maastricht University Medical Centre, PO Box 616, Maastricht, The Netherlands. E-mail: steven.oldedamink@ah.unimaas.nl Publication data Submitted 12 June 2008 First decision 30 June 2008 Resubmitted 30 December 2008 Resubmitted 8 January 2009 Accepted 9 January 2009 Epub Accepted Article 17 January 2009 SUMMARY Background Upper gastrointestinal (UGI) bleeding in patients with cirrhosis of the liver induces hyperammonaemia and leads to a catabolic cascade that precipitates life-threatening complications. The haemoglobin molecule is unique because it lacks the essential amino acid isoleucine and con- tains high amounts of leucine and valine. UGI bleed therefore presents the gut with protein of very low biologic value, which may be the stim- ulus to induce net catabolism. Aim To describe the hyperammonaemic and catabolic consequences of UGI bleeding in cirrhosis. Methods A semi-structured literature search was performed using PubMed and article references. Results It has recently been proven that (‘simulation of ’) a UGI bleed in patients with cirrhosis leads to impaired protein synthesis that can be restored by intravenous infusion of isoleucine. This may have therapeutic impli- cations for the function of rapidly dividing cells and short half-life pro- teins such as clotting factors. Renal and small bowel ammoniagenesis were shown to be the most prominent causes for the hyperammonaemia that resulted from a UGI bleed. This provides an explanation for the therapeutic failure of the current clinical therapies that are aimed at large bowel-derived ammonia production. Isoleucine infusion did not diminish renal ammoniagenesis. Conclusions New pharmacological therapies to diminish postbleeding hyperammona- emia should target the altered inter-organ ammonia metabolism and promote ammonia excretion and / or increase the excretion of precursors of ammoniagenesis, e.g. L-ornithine–phenylacetate. Aliment Pharmacol Ther 29, 801–810 Alimentary Pharmacology & Therapeutics ª 2009 Blackwell Publishing Ltd 801 doi:10.1111/j.1365-2036.2009.03938.x