Nishida S, Hamada K, Nishino N, Fukushima D, Koyanagi R, Horikawa Y, Shiwa Y, Saitoh S. Efficacy of long-term rifaximin treatment for hepatic encephalopathy in the Japanese. World J Hepatol 2019; 11(6): 531-541 [PMID: 31293721 DOI: 10.4254/wjh.v11.i6.531]
Corresponding Author of This Article
Koichi Hamada, MD, Doctor, Department of Gastroenterology, Southern-Tohoku General Hospital, 7-115 Yatsuyamada, Koriyama 963-8563, Japan. koichi.hamada@mt.strins.or.jp
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Retrospective Cohort Study
Open-Access Policy of This Article
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/
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 Processing time: 51 Days and 5.5 Hours
ARTICLE HIGHLIGHTS
Research background
Hepatic encephalopathy (HE) is a complication of liver cirrhosis. Rifaximin, an antibiotic, has been reported to decrease the occurrence of overt HE and 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.
Research objectives
To determine the clinical effects of long-term rifaximin therapy in decompensated liver cirrhosis patients, with overt HE or hyperammonemia. We evaluated the relationship between the long-term use of rifaximin and its clinical effects and the size of the shunts.
Research 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 the secondary outcome measured was the safety of its long-term use as determined by its influence on portosystemic shunts.
Research results
Rifaximin did not worsen the functionality of the liver 24 wk after the treatment. Adverse events included 2 cases of diarrhea (5.3%), which improved following the intake of probiotics. There were no cases of treatment interruption due to adverse events. Serum ammonia levels were significantly decreased 2 wk after the beginning of rifaximin compared to the pretreatment levels (P = 0.002), and it remained significantly lower for up to 60 wk. Multivariate analyses revealed that the insufficient improvement in the serum ammonia level was independently associated with the maximum shunt diameter of ≥ 8.0 mm (risk ratio = 5.52, P = 0.040).
Research conclusions
The long-term use of rifaximin was found to be safe and effective in the Japanese population.
Research perspectives
In this retrospective study, we did not examine each test to diagnose minimal HE, and the improvement of minimal HE cannot be proved. Tests as the Trail Making Test should be evaluated to minimal HE in the future investigation.
