Treatment options for hepatic encephalopathy

Few formal treatment guidelines exist for managing hepatic encephalopathy. The nonabsorbable disaccharide, lactulose, is considered the first-line therapeutic agent for treating hepatic encephalopathy. Acidification of the gastrointestinal tract is the principal mechanism by which the drug inhibits production of ammonia by coliform bacteria. Elevated ammonia levels are seen in more than 80% of patients with hepatic encephalopathy. Systemic antibiotics, primarily neomycin, have also been employed to reduce bacterial production of ammonia, but associated adverse events limit their use in patients with hepatic encephalopathy. The semisynthetic, nonsystemic antibiotic, rifaximin, was approved in March 2010 by the United States Food and Drug Administration for the treatment of overt hepatic encephalopathy. Rifaximin decreases intestinal production and absorption of ammonia by altering gastrointestinal flora and is almost completely excreted unchanged in the feces. Rifaximin has been effective in improving behavioral, laboratory, mental, and intellectual abnormalities in patients with hepatic encephalopathy. The drug was compared with lactulose in well-designed clinical studies in patients with hepatic encephalopathy. Rifaximin was generally found to be equal or superior to lactulose in these studies. Although dosages have varied, most medical centers use a dosage of rifaximin 400 mg 3 times/day for hepatic encephalopathy. Recent clinical trials have used 550 mg twice/day in order to improve patient compliance. Additional clinical trials are being undertaken to further define the efficacy and safety of rifaximin in hepatic encephalopathy.