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Hepatol Res. 2018 Dec 27. doi: 10.1111/hepr.13300. [Epub ahead of print]

Rifaximin Altered Gut Microbiota Components Associated with Liver/Neuropsychological Functions in Patients with Hepatic Encephalopathy: An Exploratory Data Analysis of a Phase II/III Clinical Trials.

Author information

1
Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine.
2
Department of Hepatology, Toranomon Hospital.
3
Department of Gastroenterology and Hepatology, Kohnodai Hospital, National Center for Global Health and Medicine.
4
Department of Gastroenterology, Mishuku Hospital.
5
Department of Gastroenterology, National Center for Global Health and Medicine.
6
Department of Gastroenterology, Tokai University Hospital.
7
Development Division, ASKA Pharmaceutical Co., Ltd.
8
Third Department of Internal Medicine, Nara Medical University.
9
Shunan Memorial Hospital.
10
Division of Hepatology, Department of Internal Medicine, Iwate Medical University.

Abstract

AIMS:

Rifaximin (RFX), a non-systemic antibiotic, improves liver/neuropsychological functions in patients with hepatic encephalopathy (HE). We aimed to investigate 1) clinical profiles associated with gut bacterial loads using exploratory data analysis and 2) effects of RFX on the gut microbiota of patients with HE.

METHODS:

We analyzed the data from 17 patients with HE who underwent fecal microbiota examination in phase II/III trials in Japan. First, profiles associated with genus Streptococcus, Veillonella, and Lactobacillus loads were analyzed using classification and regression trees (CART). Second, changes in gut microbial consortia of 7 patients with HE were assessed two weeks after RFX treatment by principal component analysis.

RESULTS:

In the CART, the first and second divergence variables for each higher bacterial load were as follows: in Streptococcus, the number connection test-A ≥39.55 sec and presence of portal-systemic shunt; In Veillonella, serum potassium levels <4.75 mEq/L and total cholesterol level <129.5 mg/dL; In Lactobacillus, white blood cell counts ≥3.4 × 103 /μL and aspartate aminotransferase level ≥44.5 U/L". There was no significant change in total bacterial load before and after RFX treatment; however, there was a decrease in Streptococcus, Veillonella, and Lactobacillus counts after RFX treatment.

CONCLUSION:

We demonstrated clinical profiles associated with gut bacterial loads in patients with HE, and showed that RFX altered gut microbiota components associated with liver/neuropsychological functions. Thus, RFX may improve liver/neuropsychological functions through the regulation of the gut microbial consortia in patients with HE.

KEYWORDS:

gut flora; hepatic encephalopathy; liver cirrhosis; rifaximin; veillonella

PMID:
30589492
DOI:
10.1111/hepr.13300

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