Active Clinical Trials in Hepatic Encephalopathy: Something Old, Something New and Something Borrowed

Abstract

Hepatic encephalopathy (HE) is a potentially reversible neurocognitive syndrome that occurs in patients with acute or chronic liver disease. Currently, most of the therapies for HE aim to reduce ammonia production or increase its elimination. To date, only two agents have been approved as treatments for HE: lactulose and rifaximin. Many other drugs have also been used, but data to support their use are limited, preliminary or lacking. The aim of this review is to provide an overview and discussion of the current development of treatments for HE. Data from ongoing clinical trials in HE were obtained from the ClinicalTrials.gov website, and a breakdown analysis of studies that were active on August 19th, 2022, was performed. Seventeen registered and ongoing clinical trials for therapeutics targeting HE were identified. More than 75% of these agents are in phase II (41.2%) or in phase III (34.7%). Among them, there are many old acquaintances in the field, such as lactulose and rifaximin, some new entries such as fecal microbiota transplantation and equine anti-thymocyte globulin, an immunosuppressive agent, but also some therapies borrowed from other conditions, such as rifamycin SV MMX and nitazoxanide, two antimicrobial agents FDA approved for the treatment of some types of diarrheas or VE303 and RBX7455, two microbiome restoration therapies, currently used as treatment of high-risk Clostridioides difficile infections. If working, some of these drugs could soon be used as valid alternatives to current therapies when ineffective or be approved as novel therapeutic approaches to improve the quality of life of HE patients. Supplementary Information The online version contains supplementary material available at 10.1007/s11064-023-03916-w.

Revolutionizing Renewable Resources: Cutting-Edge Trends and Future Prospects in the Valorization of Oligosaccharides

“…Beyond its nutritional value, GOS is crucial in dietary supplements aimed at infants and the elderly, supporting gut health and overall wellness [53]. In medical contexts, lactulose, a derivative of GOS, is utilized to manage conditions such as hyperammonemia and portosystemic encephalopathy [54]. Importantly, GOS supplementation in infants has been linked to lower risks of allergic conditions, such as eczema, underscoring its potential in allergy prevention.…”

Advancements in Interventional Radiology for Managing Hepatic Encephalopathy: A Comprehensive Review

“…IR procedures, such as TIPS and spontaneous portosystemic shunts (SPSS), play a pivotal role in the development of HE, particularly among patients with chronic liver disease [41]. Techniques like shunt occlusion and TIPS reduction have shown efficacy and safety in alleviating neurological symptoms in individuals with refractory HE, focusing on managing portal-systemic shunts integral to its pathophysiology [41,42]. A review of ongoing clinical trials in HE identified 17 active studies as of August 2022, with over 75% of these trials in phase II (41.2%) or phase III (34.7%) stages [1].…”

The Mechanism of Hepatic Encephalopathy Induced by Thioacetamide Based on Metabolomics and Proteomics: A Preliminary Study

“…Hepatic encephalopathy (HE) is a syndrome of central nervous system dysfunction caused by acute and chronic liver failure or various portal systemic shunt disorders; it is based on metabolic disorder and excludes other known types of encephalopathy [ 1 ]. HE is the third most serious complication of decompensated liver cirrhosis and affects at least 30% of people with cirrhosis [ 2 ]. HE is characterized by a series of neuropsychiatric syndromes as diverse as subclinical changes and coma, including abnormal changes in cognitive function, emotion, behavior, and motor function.…”