CAMBRIDGE, MD. — Two existing medications—an antibiotic and a hypoglycemic agent—may add some strength to the poorly outfitted armamentarium for hepatic encephalopathy, Steve Solga, M.D., said at a hepatobiliary update sponsored by Johns Hopkins University.
The altered brain function of hepatic encephalopathy appears to be related to increased ammonia levels in the blood, although controversy remains on this issue. Intestinal dysmotility, common in cirrhosis, causes an overgrowth of urease-positive bacteria and increased nitrogen absorption. The impaired liver is unable to process this extra load, so ammonia levels increase.
Generally, treatment is aimed at decreasing ammonia production and absorption; neomycin and lactulose are the most common therapies. Neomycin directly decreases the gut flora, whereas lactulose decreases gut bacteria load by promoting elimination and tilts the bacterial balance toward nonammoniagenic types.
The problem, Dr. Solga said, is that while lactulose is safe, it is not as effective in resolving symptoms as is neomycin. But neomycin may not be safe for many patients.
“Some literature suggests that long-term use is associated with irreversible ototoxicity and nephrotoxicity, and that it shouldn't be given for longer than 2 weeks for hepatic encephalopathy in patients with preexisting renal impairment.”
Importantly, neither treatment has been adequately studied in well-designed randomized trials, he added.
Rifaximin, another poorly absorbed antibiotic often used for “traveler's diarrhea,” is being studied for use in hepatic encephalopathy.
“Most of the trials indicate that safety is relatively well established, but we don't have solid efficacy data yet for hepatic encephalopathy,” he said.
However, according to a 2005 review of 15 studies, rifaximin was at least as effective as lactulose and neomycin in improving neurologic symptoms and reducing blood ammonia levels (Rev. Gastroenterol. Disord. 2005;5[suppl. 1]:10–8).
The hypoglycemic agent acarbose might have some benefit for hepatic encephalopathy patients who are diabetic, he added. The drug promotes the growth of saccrolytic bacteria.
An Italian study of 107 patients found that acarbose significantly decreased blood ammonia and improved intellectual function, while controlling blood sugar (Clin. Gastroenterol. Hepatol. 2005;3:184–91).
Finally, gut flora therapy, in the form of either prebiotics or probiotics, has potential. However, this treatment is still in its infancy. There are also regulatory issues to contend with, inasmuch as it remains unclear whether probiotics are drugs or supplements.