Glycerol phenylbutyrate (GPB) decreased hepatic encephalopathy episodes in patients with cirrhosis, new study findings show.

“[GPB] is approved to treat urea cycle defects that prevent the removal of ammonia from the body,” Bruce F. Scharschmidt, MD, of Hyperion Therapeutics in San Francisco, said in a press release. “Our trial was the first to investigate the efficacy of a direct ammonia lowering agent in patients with cirrhosis and hepatic encephalopathy.”

The phase 2 study included 178 patients with cirrhosis, of whom 59 were already taking the antibiotic rifaximin (XIFAXAN, Salix Pharmaceuticals), a current treatment for hepatic encephalopathy. Researchers aimed to determine the proportion of patients with hepatic encephalopathy events after being assigned to 6mL GPB twice daily or placebo.  

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Significantly fewer patients assigned to GPB experienced hepatic encephalopathy events than did patients assigned to placebo (21% vs. 36%; P=0.02). The total number of hepatic encephalopathy events was lower in the GPB group as well (n=35 vs. 57). Further, there were 13 total hospitalizations in the GPB arm vs. 25 hospitalizations in the placebo arm. Blood levels of ammonia were significantly lower in patients assigned GPB versus placebo.

Among the participants who were not taking rifaximin at enrollment, GPB decreased the number of patients with a hepatic encephalopathy event (10% vs. 32%; P<0.01), the time to a first event (hazard ratio=0.29; P<0.01) and the total number of events (7 vs. 31; P<0.01) compared with placebo.

“Our findings provide evidence that elevated blood ammonia plays an important role in the development of hepatic encephalopathy,” Scharschmidt said. “GPB reduced the risk for hepatic encephalopathy in patients with cirrhosis and further investigation of its therapeutic potential for patients with hepatic encephalopathy is warranted.”

“This study shows that [GPB] improves the outcome among cirrhotic patients with highly recurrent hepatic encephalopathy,” Juan Cordoba, MD, and Meritxell Ventura-Cots, MD, both of the Hospital Vall Hebron in Barcelona, Spain, wrote in an accompanying editorial. “The new drug avoids the risk for sodium overload, was well tolerated and had a good safety profile.”


  1. Rockey DC et al. Hepatology. 2014;59(3):1073-1083.
  2. Cordoba J. Hepatology. 2014;59(3):764-766.

Disclosure: See study for full list of disclosures.