{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T03:01:06Z","timestamp":1785121266989,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24fk0210103"],"award-info":[{"award-number":["JP24fk0210103"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP25fk0210172"],"award-info":[{"award-number":["JP25fk0210172"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP24K18908"],"award-info":[{"award-number":["JP24K18908"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Covert hepatic encephalopathy (CHE) is associated with cognitive impairment and adverse clinical outcomes; however, randomized evidence supporting therapeutic intervention remains limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To evaluate the efficacy of rifaximin (RFX) as a treatment for CHE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this multicentre, open\u2010label randomized controlled trial, patients with CHE associated with liver cirrhosis were randomized (1:1) to receive RFX or no treatment and followed for 12\u2009weeks. The primary endpoint was the change in Stroop test performance. Secondary endpoints included NCT\u2010B scores, serum ammonia levels, cirrhosis\u2010related adverse events, and gut microbiota composition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifty patients were randomized and completed follow\u2010up. Stroop test performance improved significantly in the RFX group (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.006) but not in controls (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.400), with a trend toward greater improvement with RFX (\u0394 Stroop test: \u22124.45\u2009\u00b1\u20097.12 vs. \u22120.98\u2009\u00b1\u20095.74\u2009s;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.056). Among patients not receiving synthetic disaccharides at baseline, improvement was significantly greater with RFX (\u0394 Stroop test: \u22123.73\u2009\u00b1\u20095.96 vs. \u22120.80\u2009\u00b1\u20095.86\u2009s;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.049). No significant changes were observed in NCT\u2010B scores or serum ammonia levels. Cirrhosis\u2010related adverse events were significantly reduced in the RFX group (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.006). Overall, gut microbial diversity did not differ between groups; however, RFX selectively altered specific taxa, including loss of the\n                      <jats:italic>[Eubacterium] brachy<\/jats:italic>\n                      group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>RFX improved cognitive performance assessed by the Stroop test and reduced cirrhosis\u2010related adverse events in patients with CHE. These randomized data support RFX as an effective therapeutic option and highlight the Stroop test as a sensitive endpoint for treatment response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apt.70712","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T03:36:22Z","timestamp":1778124982000},"page":"379-389","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Rifaximin Improves Cognitive Performance and Reduces Cirrhosis\u2010Related Adverse Events in Covert Hepatic Encephalopathy: A Randomized Controlled Trial"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3456-6921","authenticated-orcid":false,"given":"Hiroki","family":"Inada","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Faculty of Life Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshinori","family":"Toyota","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Faculty of Life Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruki","family":"Uojima","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Faculty of Life Sciences Kumamoto University  Kumamoto Japan"},{"name":"Department of Gastroenterology, Internal Medicine Kitasato University School of Medicine  Sagamihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etsuko","family":"Iio","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Faculty of Life Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6373-260X","authenticated-orcid":false,"given":"Takao","family":"Miwa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology\/Internal Medicine, Graduate School of Medicine Gifu University  Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Miuma","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiho","family":"Miyase","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Kumamoto Shinto General Hospital  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Mizuta","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Faculty of Life Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiki","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Faculty of Life Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuya","family":"Nagaoka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Faculty of Life Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8647-9486","authenticated-orcid":false,"given":"Satoshi","family":"Narahara","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Faculty of Life Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sotaro","family":"Kurano","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Faculty of Life Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Faculty of Life Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Yoshimaru","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Faculty of Life Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehisa","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Faculty of Life Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichiro","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Internal Medicine Kitasato University School of Medicine  Sagamihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4151-5663","authenticated-orcid":false,"given":"Hisashi","family":"Hidaka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Internal Medicine Kitasato University School of Medicine  Sagamihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Sugi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology National Hospital Organization Kumamoto Medical Center  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7955-1806","authenticated-orcid":false,"given":"Hiroko","family":"Setoyama","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Faculty of Life Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1151-2058","authenticated-orcid":false,"given":"Masahito","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology\/Internal Medicine, Graduate School of Medicine Gifu University  Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiro","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, Faculty of Agriculture Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2473-6966","authenticated-orcid":false,"given":"Yasuhito","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Faculty of Life Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.31250"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0973-6883(11)60126-6"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.05.042"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2022.114696"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1665-2681(19)32153-2"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11938-006-0003-x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.14022"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jceh.2018.08.001"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24423"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13568"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2011.04590.x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.07.013"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26309"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2014.05.011"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.06.001"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.13629"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000000603"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22032"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2015.11.007"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2007.01424.x"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2010.413"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3892\/br.2016.702"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.13731"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2014.264"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2015.04.016"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27210"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0907893"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0060042"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.761192"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2025.06.019"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0105592"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00203-015-1125-0"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2020.1802866"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.12938\/bmfh.2021-081"}],"container-title":["Alimentary Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apt.70712","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/apt.70712","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apt.70712","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T05:24:38Z","timestamp":1783833878000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apt.70712"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,6]]},"references-count":34,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1111\/apt.70712"],"URL":"https:\/\/doi.org\/10.1111\/apt.70712","archive":["Portico"],"relation":{},"ISSN":["0269-2813","1365-2036"],"issn-type":[{"value":"0269-2813","type":"print"},{"value":"1365-2036","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,6]]},"assertion":[{"value":"2026-01-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}