Hepatic encephalopathy is a well-known neuropsychiatric complication of cirrhosis with symptoms ranging from mild confusion and sleep disturbance to obtundation. It is highly associated with increased mortality and health care costs.1 As the population of patients with cirrhosis grows, so do these burdens on the health care system. Lactulose treatment has long been the standard of care,2 thought to be effective by acidifying stool and eradicating toxic metabolites created by gut flora that the cirrhotic liver is unable to clear. This therapy is widely available and inexpensive. However, with reported 20% to 30% nonresponse rate and refractory encephalopathy, additional therapies have been sought. Nonabsorbable antibiotics have been explored, with the goal of altering the gut microbiome and decreasing ammonia levels and other toxins implicated in hepatic encephalopathy. A randomized, double-blinded controlled trial from 20133 demonstrated the greater efficacy of lactulose with rifaximin compared with lactulose alone.