Retrospective Cohort Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jun 27, 2019; 11(6): 531-541
Published online Jun 27, 2019. doi: 10.4254/wjh.v11.i6.531
Efficacy of long-term rifaximin treatment for hepatic encephalopathy in the Japanese
Shinya Nishida, Koichi Hamada, Noriyuki Nishino, Daizo Fukushima, Ryota Koyanagi, Yoshinori Horikawa, Yoshiki Shiwa, Satoshi Saitoh
Shinya Nishida, Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki 215-0026, Japan
Koichi Hamada, Noriyuki Nishino, Daizo Fukushima, Ryota Koyanagi, Yoshinori Horikawa, Yoshiki Shiwa, Satoshi Saitoh, Department of Gastroenterology, Southern-Tohoku General Hospital, Koriyama 963-8563, Japan
Koichi Hamada, Ryota Koyanagi, Department of Minimally Invasive Surgical and Medical Oncology, Fukushima Medical University, Fukushima 960-1295, Japan
Satoshi Saitoh, Department of Hepatology, Toranomon Hospital, Tokyo 105-8470, Japan
Author contributions: Nishida S, Hamada K and Saitoh S designed the research; Nishida S, Hamada K, Fukushima D, Koyanagi R, Horikawa Y and Shiwa Y performed the research and collected the data; Nishida S, Hamada K and Saitoh S analyzed the data; Nishida S wrote the paper; Hamada K, Nishino N and Saitoh S revised the manuscript for important intellectual content.
Institutional review board statement: This study was approved by the Ethics Committee of the Southern-Tohoku General Hospital.
Informed consent statement: This study was retrospective in nature, thus this study received ethical approval for the use of an opt-out methodology.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
STROBE statement: The authors have read the STROBE statement, and the manuscript was prepared according to the STROBE statement checklist of items.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Koichi Hamada, MD, Doctor, Department of Gastroenterology, Southern-Tohoku General Hospital, 7-115 Yatsuyamada, Koriyama 963-8563, Japan. koichi.hamada@mt.strins.or.jp
Telephone: +81-24-9345322 Fax: +81-24-9345328
Received: May 8, 2019
Peer-review started: May 10, 2019
First decision: June 3, 2019
Revised: June 9, 2019
Accepted: June 17, 2019
Article in press: June 17, 2019
Published online: June 27, 2019
Abstract
BACKGROUND

Hepatic encephalopathy (HE) is a complication of liver cirrhosis and can result in neuropsychological and neuromuscular dysfunctions in patients. Rifaximin, an antibiotic, has been reported to decrease the occurrence of overt HE and also improve cognitive function in studies from Europe and the United States of America. There is not enough evidence of the relationship between the long-term use of rifaximin and its clinical effects in the Japanese.

AIM

To determine the clinical effects of long-term rifaximin therapy in decompensated liver cirrhosis patients, with overt HE or hyperammonemia.

METHODS

In this single-center retrospective observational cohort study, we reviewed the data of 38 patients who had taken rifaximin at the dose of 1200 mg/d for more than 24 wk. The primary outcome measured was the efficacy of long-term rifaximin use, and secondary outcome measured was the safety of its long-term use as determined by its influence on portosystemic shunts as well as Escherichia coli-related infections. Moreover, we compared the prognosis between the rifaximin group and control cases, matched for hepatic elasticity assessed by magnetic resonance ela-stography, age, and Child-Pugh classification.

RESULTS

Of the 38 patients included in the study, 12 (31.6%) had overt HE, 27 (71.1%) had complications of esophageal varices, and 9 (23.7%) had hepatocellular carcinoma (HCC). The control group was matched for age, Child-Pugh classification, liver stiffness, and presence of HCC. The median of serum ammonia level before treatment was 104 μg/dL (59-297), and 2 wk after treatment, it significantly decreased to 85 μg/dL (34-153) (P = 0.002). A significantly low value of 80.5 μg/dL (44-150) was maintained 24 wk after treatment. The long-term use of rifaximin did not cause a decline in liver function. Diarrhea occurred in 2 patients, who improved with the administration of probiotics, and there were no cases of aborted rifaximin therapy owing to adverse events. In patients with Child C, the survival was short, but there was no significant difference compared with that of the control group.

CONCLUSION

Rifaximin therapy improves overt HE. The long-term use of rifaximin in the Japanese is effective and safe.

Keywords: Hepatic encephalopathy, Rifaximin, Hepatic cirrhosis, Spontaneous portosystemic shunt, Magnetic resonance elastography, Child-Pugh classification

Core tip: This study evaluated the efficacy and safety of long-term rifaximin therapy for hepatic encephalopathy in the Japanese population. Serum ammonia level was maintained at a significantly low median value of 80.5 μg/dL (range, 44-150 μg/dL) at 24 wk after treatment, and the long-term use of rifaximin did not worsen liver function.