Hepatic encephalopathy is one of the most common complications of end stage liver cirrhosis requiring hospital admissions. Although the precise pathophysiology of hepatic encephalopathy is not well defined, data suggest that ammonia generated by the gut microbiota is the critical driver of this process.1
In a healthy individual, the liver protects the brain by converting ammonia to urea, which is excreted partly through the kidneys and partly in the colon. However, patients with liver cirrhosis have more urease-producing bacteria which is associated with increased production of ammonia, which can result in hepatic encephalopathy.
Harnessing the Gut Microbiota
Currently, rifaximin, an antibiotic, and/or lactulose, a synthetic sugar, are the standard of care for hepatic encephalopathy. Hepatic encephalopathy can still recur despite maintenance medical therapy. These patients have a poor quality of life, need almost constant supervision either by a caregiver at home or in an institution and require huge investment of health care costs for their repeated hospitalization.
There is evidence that an alteration in the gut bacterial composition may possibly improve mucosal barrier function and also reduce ammonia production, which in turn would represent a new therapeutic option for these patients with recurrent overt hepatic encephalopathy who otherwise have no other alternatives.
A Rebiotix microbiota-based MRT™ drug platform is currently undergoing feasibility testing for the treatment of hepatic encephalopathy under a physician-sponsored Investigational New Drug application.
- Kao D, Roach B, Park H, et al. Fecal microbiota transplantation in the management of hepatic encephalopathy. Hepatology. 2015; Aug 11. Epub ahead of print.