Fasting Blood Ammonia Predicts Risk and Frequency of Hepatic Encephalopathy Episodes in Patients With Cirrhosis

John M. Vierling, Masoud Mokhtarani, Robert S. Brown, Parvez Mantry, Don C. Rockey, Marwan Ghabril, Richard Rowell, Marzena Jurek, Dion F. Coakley, Bruce F. Scharschmidt

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Background & Aims: There is controversy over the use of measuring blood levels of ammonia (NH3) in the management of patients with overt hepatic encephalopathy (HE). Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
JournalClinical Gastroenterology and Hepatology
DOIs
StateAccepted/In press - 2016

Keywords

  • Cirrhosis Complications
  • GPB
  • Neurocognitive Function
  • Pharmacoeconomics
  • Portal Hypertension

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

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    Vierling, J. M., Mokhtarani, M., Brown, R. S., Mantry, P., Rockey, D. C., Ghabril, M., Rowell, R., Jurek, M., Coakley, D. F., & Scharschmidt, B. F. (Accepted/In press). Fasting Blood Ammonia Predicts Risk and Frequency of Hepatic Encephalopathy Episodes in Patients With Cirrhosis. Clinical Gastroenterology and Hepatology. https://doi.org/10.1016/j.cgh.2015.11.018