title: Pharmacotherapy for hyperammonemia.
abstract: BACKGROUND
  Hepatic encephalopathy (HE) is a serious neuropsychiatric complication that is seen in patients with liver failure. The pathogenesis of HE is not entirely understood, but several hypotheses have emerged and persisted during the years. Despite the many prevalent hypotheses, most of the existing evidence point to ammonia as the main culprit behind primary and secondary symptoms making it the center of potential therapeutic options for the treatment of HE. Most treatments of hyperammonemia target the organs and metabolic processes involved in ammonia detoxification.
  
  
  METHODS
  This article provides a review of the current targets of therapy as well as the drugs used for hyperammonemia treatment.
  
  
  CONCLUSIONS
  Lactulose and rifaximin have a proven role as measures to use for secondary prophylaxis and are the mainstay of current therapy. The use of molecular adsorbent recirculating system in patients with severe HE has been proven to be efficacious, but through mechanisms that appear to be independent of ammonia. The main challenge that faces the further development of treatments for HE is finding appropriate end points, and the next step would be to provide evidence of the effectiveness of established treatments and define the role of emerging new treatments.
authors.affiliation: UCL Institute for Liver and Digestive Health, UCL Medical School , Upper Third Floor, Royal Free Campus, Pond Street, NW3 2PF, London , UK +44 207 4332 794 ; rjalan@ucl.ac.uk.
authors.forename: Anna
authors.initials: A
authors.lastname: Hadjihambi
authors.forename: Varun
authors.initials: V
authors.lastname: Khetan
authors.forename: Rajiv
authors.initials: R
authors.lastname: Jalan
mesh_terms: D000641:Ammonia / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D006501:Hepatic Encephalopathy / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000628:therapy*; D006801:Humans; D022124:Hyperammonemia / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000628:therapy*; D007792:Lactulose / Q000627:therapeutic use; D012294:Rifamycins / Q000627:therapeutic use; D000078262:Rifaximin; D016060:Sorption Detoxification
chemical_list: D005765:Gastrointestinal Agents; D012294:Rifamycins; D007792:Lactulose; D000641:Ammonia; D000078262:Rifaximin
keywords: acute liver failure; chronic liver failure; hepatic encephalopathy; hyperammonemia; ornithine phenylacetate