{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:56:20Z","timestamp":1792007780351,"version":"4.4.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2022,7,17]],"date-time":"2022-07-17T00:00:00Z","timestamp":1658016000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/ http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Aims:<\/jats:title>\n                    <jats:p>Pruritus is associated with multiple liver diseases, particularly those with cholestasis, but the mechanism remains incompletely understood. Our aim was to evaluate serum IL\u201031 as a putative biomarker of pruritus in clinical trials of an farnesoid X receptor (FXR) agonist, cilofexor, in patients with NASH, primary sclerosing cholangitis (PSC), and primary biliary cholangitis (PBC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results:<\/jats:title>\n                    <jats:p>\n                      Serum IL\u201031 was measured in clinical studies of cilofexor in NASH, PSC, and PBC. In patients with PSC or PBC, baseline IL\u201031 was elevated compared to patients with NASH and healthy volunteers (HVs). IL\u201031 correlated with serum bile acids among patients with NASH, PBC, and PSC. Baseline IL\u201031 levels in PSC and PBC were positively correlated with Visual Analog Scale for pruritus and 5\u2010D itch scores. In patients with NASH, cilofexor dose\u2010dependently increased IL\u201031 from Week (W)1 to W24. In patients with NASH receiving cilofexor 100\u2009mg, IL\u201031 was higher in those with Grade 2\u20133 pruritus adverse events (AEs) than those with Grade 0\u20131 pruritus AEs. IL\u201031 weakly correlated with C4 at baseline in patients with NASH, and among those receiving cilofexor 100\u2009mg, changes in IL\u201031 and C4 from baseline to W24 were negatively correlated.\n                      <jats:italic toggle=\"yes\">IL\u201031<\/jats:italic>\n                      messenger RNA (mRNA) was elevated in hepatocytes from patients with PSC and NASH compared to HVs. In a humanized liver murine model, obeticholic acid increased\n                      <jats:italic toggle=\"yes\">IL\u201031<\/jats:italic>\n                      mRNA expression in human hepatocytes and serum levels of human IL\u201031.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>IL\u201031 levels correlate with pruritus in patients with cholestatic disease and NASH, with FXR agonist therapy resulting in higher serum levels in the latter group. IL\u201031 appears to derive in part from increased hepatocyte expression. These findings have therapeutic implications for patients with liver disease and pruritus.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.32599","type":"journal-article","created":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T09:18:07Z","timestamp":1654852687000},"page":"20-32","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":56,"title":["IL\u201031 levels correlate with pruritus in patients with cholestatic and metabolic liver diseases and is farnesoid X receptor responsive in NASH"],"prefix":"10.1097","volume":"77","author":[{"given":"Jun","family":"Xu","sequence":"first","affiliation":[{"name":"Gilead Sciences, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Wang","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Khoshdeli","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Peach","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jen\u2010Chieh","family":"Chuang","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Lin","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Wei","family":"Tsai","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangeetha","family":"Mahadevan","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesley","family":"Minto","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauri","family":"Diehl","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruchi","family":"Gupta","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Trauner","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyur","family":"Patel","sequence":"additional","affiliation":[{"name":"University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazen","family":"Noureddin","sequence":"additional","affiliation":[{"name":"Fatty Liver Program, Cedars\u2010Sinai Medical Center, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8553-3652","authenticated-orcid":false,"given":"Kris V.","family":"Kowdley","sequence":"additional","affiliation":[{"name":"Liver Institute Northwest, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliya","family":"Gulamhusein","sequence":"additional","affiliation":[{"name":"University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher 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