Rifaximin for Treatment of Hepatic Encephalopathy

OBJECTIVE: To review the effectiveness and safety of rifaximin in the treatment of hepatic encephalopathy (HE). DATA SOURCES: MEDLINE (1990-October 2008) was searched using the terms rifaximin, rifamycins, hepatic encephalopathy, liver cirrhosis, and acute liver failure. Other sources included the bibliographies of pertinent articles as well as programs and abstracts from infectious diseases and gastrointestinal diseases meetings. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the search were evaluated. All primary literature that addressed the efficacy and safety of rifaximin in the treatment of HE was included in this review. DATA SYNTHESIS: HE is a complex neuropsychiatric syndrome seen in patients with liver failure. It is characterized by disturbances in consciousness and behavior, personality changes, fluctuating neurologic signs, asterixis, and electroencephalographic changes. Although the etiology of HE is unknown, the accumulation of several gut-derived toxins such as mercaptans, ammonia, and benzodiazepine has been implicated. Current treatment options for HE include agents that reduce the concentration of these toxins, such as nonabsorbable disaccharides and antibiotics. Several studies have evaluated the use of rifaximin in the treatment of HE. They include a dose-finding study, 9 open-label studies, and 4 double-blind studies comparing rifaximin with either nonabsorbable disaccharides or antibiotics. Commonly used outcomes in most of these studies were changes in portal systemic encephalopathy index and the improvement in HE grade. Despite various limitations of the studies, rifaximin showed superior efficacy compared with lactulose for the treatment of HE, similar efficacy to paromomycin, and similar or greater efficacy than neomycin. Rifaximin was found to be associated with fewer hospitalizations, fewer days of hospitalization, and lower hospitalization charges than were seen with lactulose. Rifaximin also had a better tolerance profile than the comparative agents. CONCLUSIONS: Rifaximin appears to be an effective and safe treatment option for HE. Better-designed studies are needed to characterize its efficacy in the treatment of HE.