Signs of liver disease also improve in conjunction with alterations to gut flora

Some cirrhotic patients develop brain dysfunction, called hepatic encephalopathy, which causes deficits in behavior, intelligence, consciousness and neuromuscular function. When the dysfunction is minor, it is called minimal hepatic encephalopathy (MHE). Since ammonia has been shown to play a key role in overt hepatic encephalopathy, treatment options for MHE have also focused on reducing ammonia levels in the body.

A new study published in the May 2004 issue of Hepatology has shown that treating cirrhotic patients with synbiotics or fermentable fiber can alter the flora in the gut, lowering its pH levels as well as the ammonia levels in the blood. Both treatments improved clinical signs of brain and liver dysfunction. They may be useful alternatives to lactulose for the management of MHE.

Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD), published by John Wiley & Sons, Inc., is available online via Wiley InterScience at http://www.interscience.wiley.com/journal/hepatology.

To consider the effect of synbiotics and fermentable fiber on gut flora and MHE, a collaborative research team from Beijing Youan Hospital and Capital University of Medical Sciences, China, University College London, England and the Prince of Wales Hospital, Sydney, Australia conducted a pilot, placebo-controlled study of 55 individuals with MHE. Twenty of the patients were treated for 30 days with a daily symbiotic preparation. Twenty took fermentable fibers for 30 days, and fifteen received a placebo treatment for 30 days. At 30 days, all patients were re-screened for MHE. The researchers also assessed gut flora in fecal samples at day 1, day 30, and day 44. They compared their findings with the gut flora of 20 normal healthy volunteers.

After 30 days of treatment, 50 percent of patients treated with either the synbiotic preparation or fermentable fiber showed a reversal of MHE, compared to a 13 percent reversal rate in the placebo group. Furthermore, patients in both treatment groups had a lower fecal pH at day 30, along with significantly reduced levels of ammonia in their veins, and significantly reduced serum endotoxin levels.

Both treatments appeared to have significantly altered the cirrhotic patients' gut flora. At the outset of the study, the cirrhotic patients with MHE were found to have significant fecal overgrowths of E. Coli and Staphylococcus. Treatment with the synbiotic preparation reduced these levels to those of the healthy controls, while counts of non-urease producing Lactobacillus were significantly increased. Treatment with fermentable fiber alone increased non-urease producing Bifidobacterium spp and significantly reduced overgrowths of E. Coli and Fusobacterium spp. Treatment with the placebo did not alter the counts of any of the gut flora assessed.

"Our study is the first to examine the impact of synbiotics and fermentable fiber alone on MHE and other aspects of hepatic function in patients with cirrhosis," the authors report. "We conclude that treatment with synbiotics or fermentable fiber alone is an alternative to use of non- absorbable disaccharides, such as lactulose, for the management of MHE in patients with cirrhosis. Significant reductions in viable counts of potentially pathogenic gut flora occur with both treatments."

In an accompanying editorial in the same issue of Hepatology, Drs. Steven F. Solga and Anna Mae Diehl of Johns Hopkins University discuss the "impressive and exciting improvements in HE with both synbiotic therapy and fiber alone." They note that it is even more exciting that altering the gut flora may improve not only HE but also liver disease.

The researchers "have made a major contribution to the application to gut flora therapy to humans with liver disease," they write. "We expect this research to stimulate further interest in the study of gut flora therapy and the 'gut-liver' axis, because the liver does, indeed, care about the gut." 

Article: "Synbiotic Modulation of Gut Flora: Effect on Minimal Hepatic Encephalopathy in Patients With Cirrhosis." Qing Liu, Zhong Ping Duan, Da Kang Ha, Stig Bengmark, Jelica Kurtovic, and Stephen M. Riordan, Hepatology; May 2004; 39:5.

Editorial: "Gut Flora-Based Therapy in Liver Disease? The Liver Cares About the Gut." Steven F. Solga, M.D., and Anna Mae Diehl, M.D., Hepatology; May 2004; 39:5.