As a result, yesterday the U.S. Food and Drug Administration approved the drug, rifaximin, to prevent severe recurrence of the condition.
The University of Rochester Medical Center was one of 70 sites across the globe, and the only one in upstate New York, to take part in the study, which looked at a drug that has been used in Europe for many years. The results of the study were published in the March 25 issue of the New England Journal of Medicine. The study was funded by Salix Pharmaceuticals, which markets the medication.
In Rochester, 10 patients took part in the study, along with physicians and nurses in the Division of Gastroenterology and Hepatology of the Department of Medicine at the University of Rochester Medical Center. The Rochester effort was led by Benedict Maliakkal, M.D., associate professor of Medicine and medical director of Transplant Hepatology at URMC.
Maliakkal and colleagues in the United States, Canada and Russia studied 299 patients with hepatic encephalopathy, a term that describes a specific change of mental status that can occur in patients with advanced liver disease. The condition comes about because the diseased liver is unable to adequately detoxify ammonia, which is a waste product generated during protein metabolism. Ammonia and other toxins build up in the gut, enter the bloodstream and get into the brain, where at high levels they can cause symptoms like confusion, impaired memory, poor concentration, disorientation, muscle tremors, and even coma.
More than half of the patients who have cirrhosis of the liver have some form of hepatic encephalopathy, and more than 50,000 people a year in the United States are hospitalized because of the condition.
The study focused on rifaximin, an antibiotic that previously was approved in the United States only for the treatment of travelers’ diarrhea. Physicians looked at whether the medication was able to maintain remission and prevent severe recurrence of episodes of hepatic encephalopathy requiring hospitalization.
The answer was a clear “yes.” Participants who received rifaximin were about half as likely as others not on the medication to develop severe hepatic encephalopathy: 22.1 percent on the drug developed the condition, compared to 45.9 percent who received placebo. The rate of complications such as nausea, fatigue, and sleepiness was about the same in the two groups.
Importantly, most patients in the study were also on lactulose, a treatment commonly used both to treat and to prevent severe relapses of hepatic encephalopathy. But that treatment carries with it a host of unwanted side effects, including bloating, excess gas, and severe and unpredictable diarrhea, and many patients simply stop the treatment. So doctors have been searching for effective alternatives.
“Unfortunately, there is no perfect solution for patients with hepatic encephalopathy,” said Maliakkal. “Certain antibiotics like neomycin can be effective, but they can be potentially toxic to the kidneys and cause hearing loss. Lactulose is commonly used, but its side effects, such as diarrhea and bloating, are a major difficulty for patients. Rifaximin therapy looks promising as an effective way to prevent severe relapses of hepatic encephalopathy and has fewer troublesome side effects.”
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