Randomized, double-blind, controlled study of glycerol phenylbutyrate in hepatic encephalopathy

Don C. Rockey, John M. Vierling, Parvez Mantry, Marwan Ghabril, Robert S. Brown, Olga Alexeeva, Igor A. Zupanets, Vladimir Grinevich, Andrey Baranovsky, Larysa Dudar, Galyna Fadieienko, Nataliya Kharchenko, Iryna Klaryts'ka, Vyacheslav Morozov, Priya Grewal, Timothy Mccashland, K. Gautham Reddy, K. Rajender Reddy, Vasyl Syplyviy, Nathan M. BassKlara Dickinson, Catherine Norris, Dion Coakley, Masoud Mokhtarani, Bruce F. Scharschmidt, A. Ahmed, L. Balart, B. Berk, K. Brown, A. Frolov, C. Howell, O. Khrustalev, M. Lucey, B. Maliakkal, A. Mendoza, C. O'Brien, R. O'Shea, M. Porayko, V. Radchenko, R. Rahimi, N. Shah, K. Shetty, S. Sigal, G. Storozhakov, S. Zucker, H. Tobias, M. Voigt, S. Weinman, D. Wolf, K. Zhidkov, T. Zvyagintseva

Research output: Contribution to journalArticlepeer-review

109 Scopus citations


Glycerol phenylbutyrate (GPB) lowers ammonia by providing an alternate pathway to urea for waste nitrogen excretion in the form of phenylacetyl glutamine, which is excreted in urine. This randomized, double-blind, placebo-controlled phase II trial enrolled 178 patients with cirrhosis, including 59 already taking rifaximin, who had experienced two or more hepatic encephalopathy (HE) events in the previous 6 months. The primary endpoint was the proportion of patients with HE events. Other endpoints included the time to first event, total number of events, HE hospitalizations, symptomatic days, and safety. GPB, at 6 mL orally twice-daily, significantly reduced the proportion of patients who experienced an HE event (21% versus 36%; P=0.02), time to first event (hazard ratio [HR]=0.56; P<0.05), as well as total events (35 versus 57; P=0.04), and was associated with fewer HE hospitalizations (13 versus 25; P=0.06). Among patients not on rifaximin at enrollment, GPB reduced the proportion of patients with an HE event (10% versus 32%; P<0.01), time to first event (HR=0.29; P<0.01), and total events (7 versus 31; P<0.01). Plasma ammonia was significantly lower in patients on GPB and correlated with HE events when measured either at baseline or during the study. A similar proportion of patients in the GPB (79%) and placebo groups (76%) experienced adverse events. Conclusion: GPB reduced HE events as well as ammonia in patients with cirrhosis and HE and its safety profile was similar to placebo. The findings implicate ammonia in the pathogenesis of HE and suggest that GPB has therapeutic potential in this population. (Clinicaltrials.gov, NCT00999167). (Hepatology 2014;59:1073-1083).

Original languageEnglish (US)
Pages (from-to)1073-1083
Number of pages11
Issue number3
StatePublished - Mar 2014
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology


Dive into the research topics of 'Randomized, double-blind, controlled study of glycerol phenylbutyrate in hepatic encephalopathy'. Together they form a unique fingerprint.

Cite this