Probiotics Alleviate Symptoms of Minimal Hepatic Encephalopathy

Kristina Rebelo

November 18, 2009

November 18, 2009 (San Diego, California) — Estimates indicate that between 30% and 80% of patients with cirrhosis have a neuropsychiatric dysfunction that manifests as neurocognitive and psychomotor deficits, known as minimal hepatic encephalopathy (MHE). Results of a meta-analysis of randomized controlled trials presented here at the American College of Gastroenterology 2009 Annual Scientific Meeting indicate that probiotics have the potential to become first-line therapy for this patient population.

It is believed that gut-produced ammonia plays a key role in the pathogenesis of MHE because of the failure of the diseased liver to clear toxic products, similar to hepatic encephalopathy, lead investigator Sandhya Shukla, MD, internal medicine resident, State University of New York, Buffalo, told Medscape Gastroenterology in an interview during her poster presentation

"There is an urgent need to diagnose and treat MHE. Even though clinically, MHE doesn't manifest, when you do the complex psychomotor tests, the condition becomes obvious," she said. "MHE is epidemic in cirrhotic patients."

Societal Concerns

Dr. Shukla said that the gravest societal concerns are the poor driving skills and higher risk of automobile accidents and citations within this group, a subject reported on by Medscape Gastroenterology Viewpoints earlier this year. Prior work has been done in the area of evaluating probiotics in MHE in a small number of patients with short treatment duration; however, this is the first study to perform a systematic review to evaluate the role of probiotics and actually reach the conclusion that probiotics can reverse the characteristics of MHE, Dr. Shukla noted.

Her team searched Medline, EMBASE, and the Cochrane Controlled Trials Register to assess the value of probiotic therapy.

Among 56 randomized controlled trials found in the search, 3 fit the inclusion criteria; they involved 140 patients with MHE who were randomly assigned to receive either probiotics (n = 78) or placebo (n = 76) for a mean duration of 4.2 months.

Dr. Shukla reported that treatment with probiotics was associated with an overall risk reduction of 0.54 (95% confidence interval, 0.423 – 0.70; P < .0001).Symptom reduction correlated with a significant reduction in serum ammonia levels, with a standardized mean difference of −3.21 (95% confidence interval, −6.15 to −0.26).

There was a significant reduction in venous ammonia levels with the use of probiotics. Probiotics will alter the gut flora, according to Dr. Shukla and colleagues, replacing the pathogenic urease-producing species with nonpathogenic, non-urease-producing lactobacilli.

Dr. Shukla warned that because of the heterogeneity of the patients, results should be interpreted with a modicum of caution. She said another study limitation was that even among hepatologists, there was no standard definition of MHE.

Future studies, Dr. Shukla said, will include an adequately powered randomized controlled trial conducted over a longer duration to better understand the long-term effects of probiotics on the course of MHE.

Everybody Is a Little Nervous

William D. Carey, MD, director of the Hepatology (Liver) Center in the Department of Gastroenterology at the Cleveland Clinic in Ohio, who attended the poster presentation but was not affiliated with the study, told Medscape Gastroenterology that MHE has many social implications for the patient and for the community. "These people pose a risk for driving," he said, "and they have more citations and accidents."

He added, "I think [management of MHE] this is a very emerging field within hepatology, and certainly the general physicians taking care of patients are probably underinformed about this. Everybody is a little nervous about what the lawyer will say about the risk to physicians having a higher responsibility to report patients to the motor vehicle department."

Dr. Carey said that to date, he has not put his MHE patients on probiotics, but he is tempted to do so. "The question is, there's no data yet that such therapy would reduce driving errors and motor vehicle accidents or citations. That's a fertile area for further research."

Dr. Shukla and her colleagues and Dr. Carey have disclosed no relevant financial relationships.

American College of Gastroenterology 2009 Annual Scientific Meeting: Abstract 191. Presented October. 25, 2009.