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Probiotic Yogurt for the Treatment of Minimal Hepatic Encephalopathy

Bajaj, Jasmohan S., M.B.B.S., M.D., M.S.1; Saeian, Kia, M.D., M.S.1; Christensen, Kenneth M., P.A.-C.1; Hafeezullah, Muhammad, M.B.B.S.1; Varma, Rajiv R., M.D.1; Franco, Jose, M.D.1; Pleuss, Joan A., R.D.2; Krakower, Glenn, Ph.D.2; Hoffmann, Raymond G., Ph.D.3; Binion, David G., M.D.1

American Journal of Gastroenterology: July 2008 - Volume 103 - Issue 7 - p 1707–1715
ORIGINAL CONTRIBUTION: Liver
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OBJECTIVES Minimal hepatic encephalopathy (MHE), the preclinical stage of overt hepatic encephalopathy (OHE), is a significant condition affecting up to 60% of cirrhotics. All MHE therapies modify gut microflora, but consensus regarding MHE treatment and long-term adherence studies is lacking. The aim was to determine the effect of probiotic supplementation in the form of a food item, probiotic yogurt, on MHE reversal and adherence.

METHODS Nonalcoholic MHE cirrhotics (defined by a standard psychometric battery) were randomized with unblinded allocation to receive probiotic yogurt (with proven culture stability) or no treatment (no Rx) for 60 days in a 2:1 ratio. Quality of life (short form [SF]-36), adherence, venous ammonia, model of end-stage liver disease (MELD) scores, and inflammatory markers (tumor necrosis factor [TNF]-α, interleukin [IL]-6) were also measured. Outcomes were MHE reversal using blinded scoring, OHE development, and adherence.

RESULTS Twenty-five patients (17 yogurt, 8 no Rx; 84% Child class A) were enrolled. A significantly higher percentage of yogurt patients reversed MHE compared to no Rx patients (71%vs 0%, P= 0.003, intention-to-treat). Yogurt patients demonstrated a significant improvement in number connection test-A (NCT-A), block design test (BDT), and digit symbol test (DST) compared to baseline/no Rx group. Twenty-five percent of no Rx versus 0% of yogurt patients developed OHE during the trial. Eighty-eight percent of yogurt patients were adherent. No adverse effects or change in covariates were observed. All patients who completed the yogurt arm were agreeable to continue yogurt for 6 months if needed.

CONCLUSIONS This trial demonstrated a significant rate of MHE reversal and excellent adherence in cirrhotics after probiotic yogurt supplementation with potential for long-term adherence.

1Division of Gastroenterology and Hepatology; 2General Clinical Research Center; and 3Department of Biostatistics, Medical College of Wisconsin, Milwaukee, Wisconsin

Reprint requests and correspondence: Jasmohan S. Bajaj, M.B.B.S., M.D., M.S., Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 9200 W. Wisconsin Ave, Milwaukee, WI 53226.

CONFLICT OF INTEREST

Guarantor of the article: Jasmohan S. Bajaj, M.B.B.S., M.D., MS.

Specific author contributions: Kia Saeian, Jose Franco, Rajiv R. Varma, Kenneth M. Christensen, Joan A. Pleuss, Glenn Krakower, and Muhammad Hafeezullah were involved in the data collection and conduct of the study. David G. Binion and Kia Saeian were involved in drafting and conceptualization of the study. Raymond G. Hoffmann was involved in statistical analysis and drafting of the manuscript.

Financial support: The General Clinical Research Center at the Medical College of Wisconsin sponsored by the NIH (grant MO1 RR00058) supported this study.

Potential competing interests: None.

Received December 3, 2007; accepted January 25, 2008.

© The American College of Gastroenterology 2008. All Rights Reserved.
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