New Therapeutic Strategy for Early-Stage Hepatic Encephalopathy: Rifaximin Improves Cognitive Performance

・In patients with covert hepatic encephalopathy, it was revealed through a multi-center randomized controlled trial that the antibiotic Rifaximin is effective in improving cognitive function.

・Rifaximin reduced the risk of events associated with the progression of hepatic encephalopathy, such as falls and driving accidents, suggesting a potential contribution to improving the QOL and prognosis of patients with liver cirrhosis.

・Because it acts on specific bacteria while maintaining the overall diversity of the gut microbiome, it is expected to be a new therapeutic strategy that does not significantly disturb the gut environment, allowing for early intervention and broader clinical application.

(Overview)
A research team including Specially Appointed Assistant Professor Hiroki Inada, Associate Professor Haruki Ueshima, and Professor Yasuhito Tanaka of the Graduate School of Medical Sciences at Kumamoto University, Professor Hiroshi Hidaka of the Kitasato University School of Medicine, and Professor Jiro Nakayama of the Faculty of Agriculture at Kyushu University conducted a randomized controlled trial targeting patients with covert hepatic encephalopathy. They revealed that Rifaximin, a gut-selective antibiotic, improves cognitive function and reduces the frequency of complications related to hepatic encephalopathy.

In this study, cognitive function was evaluated using the Stroop test, combined with analysis of the gut microbiome, to demonstrate the clinical effects of Rifaximin and a portion of its mechanism of action. These results demonstrate the potential for a new therapeutic strategy for covert hepatic encephalopathy, a stage before symptoms become clinically apparent.

The research findings were published in the electronic version of the gastroenterology journal 'Alimentary Pharmacology & Therapeutics' on May 6, 2026.

(Explanation)
[Background]
Hepatic encephalopathy is a neuropsychiatric symptom associated with conditions such as liver cirrhosis, leading to a decline in concentration and judgment. 'Covert hepatic encephalopathy' is the initial stage, known to cause not only a decline in QOL due to cognitive impairment, such as risks of driving accidents, falls, and sleep disorders, but also to affect the worsening of hepatic encephalopathy and the patient's prognosis. While the need for early intervention at the covert stage has been pointed out, evidence for effective treatments has been insufficient.

[Study Content]
In this study, a randomized controlled trial was conducted by randomly assigning patients diagnosed with covert hepatic encephalopathy to a Rifaximin administration group and a non-administration group. Cognitive function was evaluated using the Stroop test, and adverse events related to hepatic encephalopathy and changes in the gut microbiome were comprehensively analyzed.

[Results]
Rifaximin significantly improved cognitive function in covert hepatic encephalopathy and reduced the incidence of events such as falls and traffic accidents. While the overall diversity of the gut microbiome was maintained, selective changes in specific bacterial groups were observed. These results suggest that the drug may act on the 'gut-brain-liver axis,' where the brain, gut, and liver interact with each other, without significantly disturbing the gut environment.

[Future Prospects]
This study demonstrates the usefulness of therapeutic intervention at the 'pre-symptomatic stage' of covert hepatic encephalopathy, providing results that support the need for reviewing future treatment strategies and the importance of early intervention. In the future, reflection in clinical guidelines is expected through larger-scale verification studies.