{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:48:56Z","timestamp":1792788536782,"version":"4.5.0"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T00:00:00Z","timestamp":1647216000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Norgine Denmark","award":["2014RH"],"award-info":[{"award-number":["2014RH"]}]},{"name":"Department of Hepatology, Rigshospitalet"},{"name":"Norgine Denmark","award":["2014RH"],"award-info":[{"award-number":["2014RH"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background and aims<\/jats:title>\n                    <jats:p>Alcoholic hepatitis (AH) is characterized by acute liver failure, neurocognitive impairment and renal failure. Severe inflammatory reactions are also known to occur in AH. Inflammation and bacterial translocation in the gut are thought to have major impact on disease development and progression. The mortality rate for AH is close to 50%. We aimed to assess the efficacy of rifaximin in treating AH and its impact on inflammation and metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The trial was approved by relevant authorities (EudraCT no: 2014-02264-33, Scientific Ethics Committee, jr. no: H-1-2014-056). Primary outcomes were changes in metabolic and inflammatory markers. Secondary outcomes were portal hypertension, kidney and neurocognitive function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Thirty-two patients were randomized to standard medical therapy (SMT) or SMT plus rifaximin, allocation was concealed. Four patients in the SMT group and five patients in the SMT + rifaximin group died due to AH and liver failure. No adverse events related to the study medication were observed. We found no significant differences in amino acids or inflammation markers (IL-2, IL-6, IL-8, IL-10, TNF-\u03b1, interferon-\u03b3) between the groups after 28 and 90 days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Rifaximin does not alter inflammation or metabolism in patients with AH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0264278","type":"journal-article","created":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T13:26:18Z","timestamp":1647264378000},"page":"e0264278","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":31,"title":["The impact of rifaximin on inflammation and metabolism in alcoholic hepatitis: A randomized clinical trial"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4807-1575","authenticated-orcid":true,"given":"Nina","family":"Kimer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mads","family":"Meldgaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole","family":"Hamberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thit Mynster","family":"Kronborg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan M.","family":"Lund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger Jon","family":"M\u00f8ller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flemming","family":"Bendtsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henriette","family":"Ytting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,3,14]]},"reference":[{"key":"pone.0264278.ref001","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1053\/j.gastro.2014.01.018","article-title":"A histologic scoring system for prognosis of patients with alcoholic hepatitis","volume":"146","author":"J Altamirano","year":"2014","journal-title":"Gastroenterology"},{"key":"pone.0264278.ref002","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nrgastro.2015.35","article-title":"Alcoholic liver disease: Mechanisms of injury and targeted treatment","author":"A Louvet","year":"2015","journal-title":"Nature Reviews Gastroenterology and Hepatology"},{"issue":"6","key":"pone.0264278.ref003","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1002\/hep.21607","article-title":"The Lille model: A new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids","volume":"45","author":"A Louvet","year":"2007","journal-title":"Hepatology"},{"issue":"3","key":"pone.0264278.ref004","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/apt.15376","article-title":"Systematic review with meta-analysis: high mortality in patients with non-severe alcoholic hepatitis","volume":"5","author":"K Bennett","year":"2019","journal-title":"Aliment Pharmacol Ther"},{"key":"pone.0264278.ref005","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1016\/S0140-6736(15)60337-3","article-title":"Acute alcoholic hepatitis and cellular Th1 immune responses to alcohol dehydrogenase","volume":"385","author":"LJ Blackmore","year":"2015","journal-title":"Lancet"},{"issue":"5","key":"pone.0264278.ref006","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1016\/j.jhep.2018.06.019","article-title":"Prevalent acute-on-chronic liver failure and response to corticosteroids in alcoholic hepatitis","volume":"69","author":"EH Forrest","year":"2018","journal-title":"J Hepatol"},{"issue":"1","key":"pone.0264278.ref007","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.jhep.2013.07.044","article-title":"Pathological bacterial translocation in liver cirrhosis","volume":"60","author":"R Wiest","year":"2014","journal-title":"J Hepatol"},{"issue":"7","key":"pone.0264278.ref008","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1053\/j.gastro.2013.02.042","article-title":"Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis","volume":"144","author":"R Moreau","year":"2013","journal-title":"Gastroenterology"},{"issue":"3","key":"pone.0264278.ref009","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1002\/hep.20632","article-title":"Bacterial translocation (BT) in cirrhosis","volume":"41","author":"R Wiest","year":"2005","journal-title":"Hepatology"},{"issue":"3","key":"pone.0264278.ref010","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.jhep.2008.10.028","article-title":"Evidence that chronic alcohol exposure promotes intestinal oxidative stress, intestinal hyperpermeability and endotoxemia prior to development of alcoholic steatohepatitis in rats","volume":"50","author":"A Keshavarzian","year":"2009","journal-title":"J Hepatol"},{"issue":"10","key":"pone.0264278.ref011","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1111\/j.1530-0277.2009.01022.x","article-title":"Intestinal dysbiosis: A possible mechanism of alcohol-induced endotoxemia and alcoholic steatohepatitis in rats","volume":"33","author":"E Mutlu","year":"2009","journal-title":"Alcohol Clin Exp Res"},{"issue":"4","key":"pone.0264278.ref012","first-page":"317","article-title":"Cytokines and alcoholic liver disease","volume":"21","author":"CJ McClain","year":"1997","journal-title":"Alcohol Res Heal"},{"key":"pone.0264278.ref013","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1007\/BF01691128","article-title":"Bacterial DNA as an evolutionary conserved ligand signalling danger of infection to immune cells","volume":"17","author":"K Heeg","year":"1998","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"pone.0264278.ref014","first-page":"29","article-title":"Relation of endotoxin, endotoxin binding proteins and macrophages to severe alcoholic liver injury and multiple organ failure","author":"H. Fukui","year":"2005","journal-title":"Alcohol Clin Exp Res"},{"issue":"4","key":"pone.0264278.ref015","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1002\/hep.28740","article-title":"Systemic inflammation in decompensated cirrhosis: Characterization and role in acute-on-chronic liver failure","volume":"64","author":"J Claria","year":"2016","journal-title":"Hepatology"},{"issue":"2","key":"pone.0264278.ref016","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/0168-8278(95)80424-2","article-title":"Endotoxemia in patients with chronic liver diseases: relationship to severity of liver diseases, presence of esophageal varices, and hyperdynamic circulation","volume":"22","author":"RS Lin","year":"1995","journal-title":"J Hepatol"},{"issue":"11","key":"pone.0264278.ref017","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1016\/j.bcp.2006.04.011","article-title":"NF-\u03baB activation by reactive oxygen species: Fifteen years later","volume":"72","author":"G Gloire","year":"2006","journal-title":"Biochem Pharmacol"},{"issue":"42","key":"pone.0264278.ref018","doi-asserted-by":"crossref","first-page":"11904","DOI":"10.3748\/wjg.v21.i42.11904","article-title":"Immune dysfunction in acute alcoholic hepatitis","volume":"21","author":"AD Dhanda","year":"2015","journal-title":"World J Gastroenterol"},{"issue":"12","key":"pone.0264278.ref019","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1056\/NEJMoa0907893","article-title":"Rifaximin treatment in hepatic encephalopathy","volume":"362","author":"NM Bass","year":"2010","journal-title":"N Engl J Med"},{"issue":"14","key":"pone.0264278.ref020","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.3748\/wjg.v18.i14.1700","article-title":"Rifaximin for the prevention of spontaneous bacterial peritonitis","volume":"18","author":"GN Kalambokis","year":"2012","journal-title":"World J Gastroenterol"},{"issue":"Suppl 1","key":"pone.0264278.ref021","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/apt.13435","article-title":"Review article: potential mechanisms of action of rifaximin in the management of hepatic encephalopathy and other complications of cirrhosis","volume":"43","author":"JS Bajaj","year":"2016","journal-title":"Aliment Pharmacol Ther"},{"key":"pone.0264278.ref022","unstructured":"Commission E. The Rules Governing Medicinal Products in the European Union [Internet]. EU GMP Annex 13: Investigational Medicinal Products. 2010 [cited 2021 Jul 1]. p. 1\u201319. Available from: https:\/\/www.gmp-compliance.org\/files\/guidemgr\/2009_06_annex13.pdf"},{"issue":"5","key":"pone.0264278.ref023","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/S0168-8278(01)00026-5","article-title":"Neuropsychological characterization of hepatic encephalopathy","volume":"34","author":"K Weissenborn","year":"2001","journal-title":"J Hepatol"},{"issue":"11","key":"pone.0264278.ref024","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1111\/j.1572-0241.2008.02104.x","article-title":"A new scoring system for prognostic stratification of patients with alcoholic hepatitis","volume":"103","author":"M Dominguez","year":"2008","journal-title":"Am J Gastroenterol"},{"issue":"2","key":"pone.0264278.ref025","doi-asserted-by":"crossref","DOI":"10.1053\/j.gastro.2015.04.044","article-title":"Combining data from liver disease scoring systems better predicts outcomes of patients with alcoholic hepatitis","volume":"149","author":"A Louvet","year":"2015","journal-title":"Gastroenterology"},{"key":"pone.0264278.ref026","article-title":"Variability of hydrostatic hepatic vein and ascitic fluid pressure, and of plasma and ascitic fluid colloid osmotic pressure in patients with liver cirrhosis","author":"JH Henriksen","year":"1980","journal-title":"Scand J Clin Lab Invest"},{"issue":"4","key":"pone.0264278.ref027","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1080\/003655102760145852","article-title":"Characterization of an enzyme-linked immunosorbent assay for soluble CD163","volume":"62","author":"HJ Moller","year":"2002","journal-title":"Scand J Clin Lab Invest"},{"key":"pone.0264278.ref028","unstructured":"Mesoscale.com. MSD Multispot Assay asystem [Internet]. https:\/\/www.mesoscale.com\/en\/products\/v-plex-proinflammatory-panel-1-human-kit-k15049d\/. [cited 2021 Mar 25]. Available from: https:\/\/www.mesoscale.com\/~\/media\/files\/product inserts\/proinflammatory panel 1 human insert.pdf"},{"key":"pone.0264278.ref029","article-title":"EASL clinical practical guidelines: Management of alcoholic liver disease","author":"P Mathurin","year":"2012","journal-title":"Journal of Hepatology"},{"key":"pone.0264278.ref030","article-title":"EASL Clinical Practice Guidelines: Management of alcohol-related liver disease","author":"M Thursz","year":"2018","journal-title":"J Hepatol"},{"issue":"7","key":"pone.0264278.ref031","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/j.cgh.2012.02.025","article-title":"Rifaximin improves systemic hemodynamics and renal function in patients with alcohol-related cirrhosis and ascites","volume":"10","author":"GN Kalambokis","year":"2012","journal-title":"Clin Gastroenterol Hepatol"},{"issue":"3","key":"pone.0264278.ref032","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1111\/jgh.12070","article-title":"Long-term administration of rifaximin improves the prognosis of patients with decompensated alcoholic cirrhosis","volume":"28","author":"J Vlachogiannakos","year":"2013","journal-title":"J Gastroenterol Hepatol"},{"issue":"9","key":"pone.0264278.ref033","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1111\/j.1365-2036.2009.03958.x","article-title":"Intestinal decontamination improves liver haemodynamics in patients with alcohol-related decompensated cirrhosis","volume":"29","author":"J Vlachogiannakos","year":"2009","journal-title":"Aliment Pharmacol Ther"},{"issue":"2","key":"pone.0264278.ref034","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1002\/hep.28898","article-title":"Rifaximin has no effect on hemodynamics in decompensated cirrhosis: A randomized, double-blind, placebo-controlled trial","volume":"65","author":"N Kimer","year":"2017","journal-title":"Hepatology"},{"issue":"1","key":"pone.0264278.ref035","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1111\/jgh.13852","article-title":"Rifaximin has minor effects on bacterial composition, inflammation, and bacterial translocation in cirrhosis: A randomized trial","volume":"33","author":"N Kimer","year":"2018","journal-title":"J Gastroenterol Hepatol"},{"issue":"1","key":"pone.0264278.ref036","doi-asserted-by":"crossref","first-page":"371","DOI":"10.2741\/2070","article-title":"Glutamine metabolism and signaling in the liver","volume":"12","author":"D H\u00e4ussinger","year":"2007","journal-title":"Front Biosci"},{"issue":"2","key":"pone.0264278.ref037","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1113\/jphysiol.2006.126029","article-title":"Intestinal and hepatic metabolism of glutamine and citrulline in humans","volume":"581","author":"MCG Van De Poll","year":"2007","journal-title":"J Physiol"},{"key":"pone.0264278.ref038","article-title":"Balance between pro and anti-inflammatory cytokines in patients with acute alcoholic hepatitis","author":"S Naveau","year":"2005","journal-title":"Gastroenterol Clin Biol"},{"issue":"3","key":"pone.0264278.ref039","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1053\/j.gastro.2014.11.041","article-title":"Blockade of PD1 and TIM3 restores innate and adaptive immunity in patients with acute alcoholic hepatitis","volume":"148","author":"LJL Markwick","year":"2015","journal-title":"Gastroenterology"},{"issue":"1","key":"pone.0264278.ref040","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.gene.2012.07.077","article-title":"Genetic variants of TNF\u03b1, IL10, IL1\u03b2, CTLA4 and TGF\u03b21 modulate the indices of alcohol-induced liver injury in East Indian population","volume":"509","author":"N Roy","year":"2012","journal-title":"Gene"},{"issue":"4","key":"pone.0264278.ref041","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1111\/apt.16200","article-title":"Microbiome as a potential diagnostic and predictive biomarker in severe alcoholic hepatitis","volume":"53","author":"SS Kim","year":"2021","journal-title":"Aliment Pharmacol Ther"},{"issue":"3","key":"pone.0264278.ref042","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1002\/hep.31708","article-title":"The use of Rifaximin in Patients with Cirrhosis","volume":"74","author":"P Caraceni","year":"2021","journal-title":"Hepatology"},{"issue":"8","key":"pone.0264278.ref043","doi-asserted-by":"crossref","first-page":"e187","DOI":"10.1038\/ctg.2016.44","article-title":"Rifaximin Exerts Beneficial Effects Independent of its Ability to Alter Microbiota Composition","volume":"7","author":"DJ Kang","year":"2016","journal-title":"Clin Transl Gastroenterol"},{"key":"pone.0264278.ref044","doi-asserted-by":"crossref","first-page":"S58","DOI":"10.1016\/S0168-8278(20)30658-9","article-title":"Lipidomics profiling reveals a distinct pattern of selective lipid depletion in the circulation and liver tissue in patients with progressive alcohol-associated liver fibrosis: a biopsy-controlled study in 400 people","volume":"73","author":"M Thiele","year":"2020","journal-title":"J Hepatol"},{"issue":"2","key":"pone.0264278.ref045","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1002\/hep.31256","article-title":"Circulating Extracellular Vesicles Carrying Sphingolipid Cargo for the diagnosis and Dynamic Risk Profiling of Alcoholic Hepatitis","volume":"73","author":"T Sehrawat","year":"2021","journal-title":"Hepatology"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0264278","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T15:35:15Z","timestamp":1700321715000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0264278"}},"subtitle":[],"editor":[{"given":"Wan-Long","family":"Chuang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,3,14]]},"references-count":45,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0264278","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,14]]}}}