Trial reportHepatology (Baltimore, Md.)2014
Randomized, double-blind, controlled study of glycerol phenylbutyrate in hepatic encephalopathy.
Trial report in Hepatology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 58 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of HPN-100 for Maintaining Remission in Subjects With Cirrhosis and Episodic Hepatic Encephalopathy
Effect of Polyethylene Glycol Versus Lactulose on Hepatic Encephalopathy in Patients With Liver Cirrhosis; a Randomized Clinical Trial (PEGHE Trial)
Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 158 citations in OpenAlex.
- Pharmacotherapies that specifically target ammonia for the prevention and treatment of hepatic encephalopathy in adults with cirrhosis.The Cochrane database of systematic reviews · 2019Pooled it
- Covert hepatic encephalopathy as a multi-organ syndrome: the gut-liver-muscle-brain axis, diagnosis, treatment, and multidisciplinary care.Journal of gastroenterology · 2026Review
- The role of ammonia in chronic liver disease.Hepatology communications · 2026Review
- Advances in understanding, diagnosing, and treating hepatic encephalopathy: from epidemiology to emerging therapies.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- A Mysterious Case of Recurrent Confusion: An Unusual Presentation of Congenital Intrahepatic Portosystemic Shunt.Cureus · 2025Article
- Golexanolone Attenuates Neuroinflammation, Fatigue, and Cognitive and Motor Impairment in Diverse Neuroinflammatory Disorders.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Hepatic Encephalopathy: Current Thoughts on Pathophysiology and Management.Current neurology and neuroscience reports · 2025Review
- Glutamine metabolism and ammonia death: targeted modulation for enhanced cancer immunotherapy.Frontiers in immunology · 2025Review
- Down the road towards hepatic encephalopathy. The elusive ammonia- what determines the arterial concentration?Metabolic brain disease · 2024Review
- Ammonia-induced lysosomal and mitochondrial damage causes cell death of effector CD8Nature cell biology · 2024Article
- Prophylaxis of hepatic encephalopathy: current and future drug targets.Hepatology international · 2024Review
- Investigation of Post-Transplant Mental Well-Being in Liver Transplant Recipients with Hepatic Encephalopathy.Journal of clinical medicine · 2024Article
- Future Therapies of Hepatic Encephalopathy.Clinics in liver disease · 2024Review
- Intensive care management of acute-on-chronic liver failure.Intensive care medicine · 2023Review
- Active Clinical Trials in Hepatic Encephalopathy: Something Old, Something New and Something Borrowed.Neurochemical research · 2023Review
- Update in the Treatment of the Complications of Cirrhosis.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2023Review
- Secondary Ammonia Scavenge With Glycerol Phenylbutyrate Improves Hyperammonemia Following Portosystemic Shunting.JPGN reports · 2022Article
- Hepatic encephalopathy.Nature reviews. Disease primers · 2022Review
- Management of Hepatic Encephalopathy Associated with Advanced Liver Disease.Clinical drug investigation · 2022Review
- Evidence-based approach to management of hepatic encephalopathy in adults.World journal of hepatology · 2022Review
Corrections and comments
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Authors and funding
26 authors at 20 institutions in 4 countries.
Funding
Abstract
unlabelledGlycerol 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.
conclusionGPB 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).
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.