glycerol-phenylbutyrate and ornithine-phenylacetate

Despite widespread use of lactulose and rifaximin for the treatment of hepatic encephalopathy, this complication of advanced liver disease remains a major burden on the health care system in the United States and continues to predispose to high morbidity and mortality. Several agents have surfaced over recent years with promise to treat hepatic encephalopathy and mitigate the cognitive impairment associated with this disease process. The purpose of this article is to highlight the leading emerging therapies in hepatic encephalopathy as well as their therapeutic targets.

Topics: Acetylcarnitine; Albumins; Ammonia; Dipeptides; Fecal Microbiota Transplantation; Flumazenil; GABA Modulators; Glycerol; Hepatic Encephalopathy; Humans; Nootropic Agents; Ornithine; Phenylbutyrates; Polyethylene Glycols; Probiotics; Surface-Active Agents

Hepatic encephalopathy is one of the most debilitating clinical manifestations of cirrhosis and associated with increased morbidity and mortality. Treatment modalities available include the nonabsorbable disaccharides (lactulose) and the nonabsorbable antibiotics (rifaximin).. Newer therapeutic targets under evaluation include ammonia scavengers (ornithine phenylacetate) and modulation of gut microbiota (fecal microbiota transplantation).. This review will focus on the pathophysiology of hepatic encephalopathy along with an update on therapeutic targets under investigation.

Topics: Amino Acids, Aromatic; Amino Acids, Branched-Chain; Ammonia; Dipeptides; Fecal Microbiota Transplantation; Frailty; Gastrointestinal Agents; Gastrointestinal Microbiome; Glycerol; Hepatic Encephalopathy; Humans; Hypertension, Portal; Lactulose; Liver Cirrhosis; Ornithine; Phenylbutyrates; Polyethylene Glycols; Probiotics; Rifaximin; Trace Elements; Zinc

Hepatic encephalopathy (HE) is a common complication of cirrhosis, leading to frequent hospitalizations. Because ammonia is thought to play an important role in the pathogenesis of HE, therapies specifically aimed at reducing ammonia levels have been developed for conditions causing hyperammonemia, including HE. Ammonia scavengers have been used in HE patients, leading to improvements in symptoms. Bowel cleansing with polyethylene glycol has also been studied recently, resulting in more rapid improvement in acute HE compared with lactulose. Extracorporeal devices have been used in cases of refractory HE but currently are used primarily in research settings and not approved for clinical management for HE.

Topics: Ammonia; Carbon; Gastrointestinal Agents; Glycerol; Hepatic Encephalopathy; Humans; Ornithine; Oxides; Phenylbutyrates; Polyethylene Glycols; Urea

Hepatic encephalopathy (HE) is defined by an altered mental status in the setting of portosystemic shunting, with or without cirrhosis. The basis of HE is probably multi-factorial, but increased ammonia delivery to the brain is thought to play a pivotal role. Medical therapies have typically focused on reducing blood ammonia concentrations. These measures are moderately effective, but further improvements will require identification of new therapeutic targets. Two medications, lactulose and rifaximin, are currently approved for the treatment of HE in the USA - new compounds are available off-label, and are in clinical trials. The presence of HE is associated with a higher risk of death in cirrhotic patients. Liver transplantation typically cures HE, but HE does not increase the MELD score, and therefore does not contribute to the likelihood of liver transplantation.

Topics: Amino Acids, Branched-Chain; Ammonia; Arteriovenous Fistula; Dipeptides; Gastrointestinal Agents; Glycerol; Hepatic Encephalopathy; Humans; Lactulose; Liver Failure; Malnutrition; Ornithine; Phenylbutyrates; Probiotics; Rifamycins; Rifaximin

Topics: Albumins; Amino Acids; Diagnosis, Differential; Diet; Disaccharides; Drug Resistance; Electroencephalography; Glycerol; Hepatic Encephalopathy; Humans; Liver Cirrhosis; Magnetic Resonance Imaging; Neomycin; Neurologic Examination; Nucleic Acid Synthesis Inhibitors; Ornithine; Phenylbutyrates; Probiotics; Protein Synthesis Inhibitors; Rifamycins; Rifaximin; Terminal Care; Tomography, X-Ray Computed