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Serum liver enzymes, insulin sensitivity by clamp like index (CLIX) and hepatic fat by proton <jats:sup>1<\/jats:sup>H\u2011MRS, MRI-PDFF and CAP were assessed. Hepatic energy metabolism and Kupffer cell function were evaluated by phosphorus <jats:sup>31<\/jats:sup>P\u2011MRS and superparamagnetic iron oxide MRI (SPIO-MRI). Other readouts included serum lipids and markers of BA metabolism\/signaling besides fecal microbiome and BA analysis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>A\u00a0significant decrease in ALT (<jats:italic>p<\/jats:italic>\u202f=\u20090.027; 1\u2011tailed) and GGT (<jats:italic>p<\/jats:italic>\u202f=\u20090.019) was observed, without changes in serum alkaline phosphatase or serum lipids. Insulin sensitivity improved in 92% of patients (<jats:italic>p<\/jats:italic>\u202f=\u20090.02). However, hepatic steatosis measured by PDFF-MRI, <jats:sup>1<\/jats:sup>H\u2011MRS and CAP besides extended serum lipoprotein and BA profiles did not change. NADPH\/\u03b3ATP ratios at <jats:sup>31<\/jats:sup>P\u2011MRS significantly decreased (<jats:italic>p<\/jats:italic>\u202f=\u20090.022) possibly reflecting reduced hepatic inflammatory stress, but SPIO-MRI remained unchanged. Reduced preponderance of Coriobacteriaceae (<jats:italic>p<\/jats:italic>\u202f=\u20090.036) correlated with a\u00a0relative reduction of total fecal BAs. There were no serious adverse events but short intervals of cardiac arrhythmia recorded in 2\u00a0patients led to termination of the study.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The non-steroidal FXR agonist PX-104 improved insulin sensitivity and liver enzymes after 4\u00a0weeks of treatment in non-diabetic NAFLD patients. Changes in fecal BAs and gut microbiota deserve more extensive investigations.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00508-020-01735-5","type":"journal-article","created":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T14:03:52Z","timestamp":1600178632000},"page":"441-451","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Open-label phase\u00a0II study evaluating safety and efficacy of the non-steroidal farnesoid X receptor agonist PX-104 in non-alcoholic fatty liver disease"],"prefix":"10.1007","volume":"133","author":[{"given":"Stefan","family":"Traussnigg","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emina","family":"Halilbasic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harald","family":"Hofer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Munda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatjana","family":"Stojakovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00fcnter","family":"Fauler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl","family":"Kashofer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Krssak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Wolzt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Trauner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,9,15]]},"reference":[{"key":"1735_CR1","doi-asserted-by":"publisher","first-page":"1723","DOI":"10.1002\/hep.28123","volume":"62","author":"ZM Younossi","year":"2015","unstructured":"Younossi\u00a0ZM, Otgonsuren\u00a0M, Henry\u00a0L, et\u00a0al. 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M.\u00a0Trauner served as a consultant for Albireo, BiomX, Falk, Genfit, Gilead, Intercept, Janssen, MSD, Novartis, Phenex and Regulus and is a member of the speakers\u2019 bureau of Falk, Gilead, Intercept MSD and Roche. He further received travel grants from AbbVie, Falk, Roche and Gilead and unrestricted research grants from Albireo, Cymabay, Falk, Intercept, MSD and Takeda. He is also co-inventor of a patent on the medical use of nor-UDCA filed by the Medical University of Graz.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures performed in studies involving human participants or on human tissue were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1975 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all patients for being included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical standards"}}]}}