title: Fasting Blood Ammonia Predicts Risk and Frequency of Hepatic Encephalopathy Episodes in Patients With Cirrhosis.
abstract: There is controversy over the use of measuring blood levels of ammonia (NH3) in the management of patients with overt hepatic encephalopathy (HE).
  
  
  
  We performed a retrospective analysis of data from a randomized, double-blind study of 178 patients with cirrhosis given glycerol phenylbutyrate (an NH3-lowering agent) or placebo for 16 weeks. Blood samples were collected at baseline and on study days 7 and 14 and NH3 levels were measured. The probabilities of having an HE episode, based on ammonia values, were modeled using binary logistic regression. A Cox proportional model was used to determine the risk of HE episodes in patients with baseline fasting NH3 levels ≤1.5-fold the upper limit of normal (ULN) versus patients with fasting NH3 levels >1.5-fold the ULN.
  
  
  
  The risk and frequency of HE episodes and HE-related hospitalizations correlated with baseline (mean, 51 ± 6 μmol/L; ULN, 35 μmol/L) and on-study fasting levels of NH3, and increased sharply at levels >1.5-fold the ULN. Regardless of baseline level, NH3 exposure and the relative risk of HE episodes were decreased by glycerol phenylbutyrate.
  
  
  
  In analysis of data from a phase 2 study of the effects of glycerol phenylbutyrate in patients with cirrhosis, we found that fasting levels of NH3 in blood can identify patients at risk for HE-related morbidity. Patients with HE might benefit from NH3-lowering therapy. ClinicalTrials.gov no: NCT 00999167.
authors.affiliation: Baylor College of Medicine, Houston, Texas.
authors.forename: John M
authors.initials: JM
authors.lastname: Vierling
authors.affiliation: Horizon Therapeutics, Inc, Lake Forest, Illinois.
authors.forename: Masoud
authors.initials: M
authors.lastname: Mokhtarani
authors.affiliation: Columbia University Medical Center, New York, New York.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Brown
authors.affiliation: Liver Institute at Methodist Dallas Medical Center, Dallas, Texas.
authors.forename: Parvez
authors.initials: P
authors.lastname: Mantry
authors.affiliation: Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Don C
authors.initials: DC
authors.lastname: Rockey
authors.affiliation: Indiana University, Indianapolis, Indiana.
authors.forename: Marwan
authors.initials: M
authors.lastname: Ghabril
authors.affiliation: Horizon Therapeutics, Inc, Lake Forest, Illinois.
authors.forename: Richard
authors.initials: R
authors.lastname: Rowell
authors.affiliation: Horizon Therapeutics, Inc, Lake Forest, Illinois.
authors.forename: Marzena
authors.initials: M
authors.lastname: Jurek
authors.affiliation: Horizon Therapeutics, Inc, Lake Forest, Illinois.
authors.forename: Dion F
authors.initials: DF
authors.lastname: Coakley
authors.affiliation: Horizon Therapeutics, Inc, Lake Forest, Illinois. Electronic address: bruce.scharschmidt@gmail.com.
authors.forename: Bruce F
authors.initials: BF
authors.lastname: Scharschmidt
mesh_terms: D000641:Ammonia / Q000097:blood*; D004311:Double-Blind Method; D005215:Fasting; D006501:Hepatic Encephalopathy / Q000453:epidemiology*; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications* / Q000175:diagnosis / Q000473:pathology*; D015233:Models, Statistical; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D018570:Risk Assessment
chemical_list: D000641:Ammonia
keywords: Cirrhosis Complications; GPB; Neurocognitive Function; Pharmacoeconomics; Portal Hypertension