title: Review article: the design of clinical trials in hepatic encephalopathy--an International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) consensus statement.
abstract: BACKGROUND
  The clinical classification of hepatic encephalopathy is largely subjective, which has led to difficulties in designing trials in this field.
  
  
  OBJECTIVE
  To review the current classification of hepatic encephalopathy and to develop consensus guidelines on the design and conduct of future clinical trials.
  
  
  METHODS
  A round table was convened at the 14th International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) meeting. Key discussion points were the nomenclature of hepatic encephalopathy and the selection of patients, standards of care and end-points for assessing the treatment and secondary prevention of hepatic encephalopathy.
  
  
  RESULTS
  It was generally agreed that severity assessment of hepatic encephalopathy in patients with cirrhosis, whether made clinically or more objectively, should be continuous rather than categorical, and a system for assessing the SONIC (Spectrum of Neuro-cognitive Impairment in Cirrhosis) was proposed. Within this system, patients currently classified as having minimal hepatic encephalopathy and Grade I hepatic encephalopathy would be classified as having Covert hepatic encephalopathy, whereas those with apparent clinical abnormalities would continue to be classified as overt hepatic encephalopathy. Some aspects of the terminology require further debate. Consensus was also reached on the patient populations, standards of care and endpoints to assess clinical trial outcomes. However, some compromises had to be made as there is considerable inter- and intravariability in the availability of some of the more objective surrogate performance markers.
  
  
  CONCLUSIONS
  The objectives of the round table were met. Robust, defendable guidelines for the conduct of future studies into hepatic encephalopathy have been provided. Outstanding issues are few and will continue to be discussed.
authors.affiliation: Virginia Commonwealth University and McGuire VA Medical Center, 1201 Broad Rock Boulevard, Richmond, VA 23249, USA. jsbajaj@vcu.edu
authors.forename: J S
authors.initials: JS
authors.lastname: Bajaj
authors.forename: J
authors.initials: J
authors.lastname: Cordoba
authors.forename: K D
authors.initials: KD
authors.lastname: Mullen
authors.forename: P
authors.initials: P
authors.lastname: Amodio
authors.forename: D L
authors.initials: DL
authors.lastname: Shawcross
authors.forename: R F
authors.initials: RF
authors.lastname: Butterworth
authors.forename: M Y
authors.initials: MY
authors.lastname: Morgan
mesh_terms: D002986:Clinical Trials as Topic / Q000592:standards*; D006501:Hepatic Encephalopathy / Q000145:classification* / Q000628:therapy; D006801:Humans; D018579:Patient Selection; D012107:Research Design / Q000592:standards*; D012720:Severity of Illness Index; D009626:Terminology as Topic