{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T07:05:01Z","timestamp":1784185501033,"version":"3.55.0"},"reference-count":36,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hepatology Research"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aim<\/jats:title>\n                    <jats:p>Pemafibrate, a selective PPAR\u03b1 modulator (SPPARM\u03b1), improves cholestatic liver enzymes in primary biliary cholangitis (PBC). However, whether these effects depend on PBC\u2010specific autoimmune mechanisms or reflect broader anti\u2010cholestatic actions remains unclear. This study evaluated the effects of pemafibrate on cholestatic markers by PBC status and explored bile acid and immunological changes in patients with PBC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This post hoc analysis used data from a 52\u2010week phase III study of pemafibrate in patients with hypertriglyceridemia, including 9 with PBC. Cholestatic markers (ALP, total bilirubin, GGT, and LAP) were assessed serially. Linear regression examined associations between baseline levels and response by PBC status. In patients with PBC, bile acids, FGF19, FGF21, C4, IgM, IgG, and M2BPGi were also evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Pemafibrate significantly reduced all cholestatic markers from week 4\u201352, regardless of the presence of PBC. Greater reductions were observed in patients with higher baseline levels. In patients with PBC, C4 decreased without significant change in FGF19, suggesting suppression of de novo bile acid synthesis independent of intestinal feedback. The bile acid profile shifted toward a more hydrophilic composition with reduced hydrophobic species. IgM, IgG, and M2BPGi decreased, whereas FGF21 increased.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Pemafibrate improved cholestatic markers in a baseline\u2010dependent manner, regardless of the presence of PBC, suggesting mechanisms beyond PBC\u2010specific pathology. These findings support a broader anti\u2010cholestatic effect, potentially mediated by coordinated modulation of bile acid metabolism and immunological activity through PPAR\u03b1 activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      The trials were registered at\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      under the identifiers NCT04716595\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/hepr.70244","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T06:25:40Z","timestamp":1784183140000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pemafibrate Improves Cholestatic Markers Regardless of the Presence of Primary Biliary Cholangitis"],"prefix":"10.1111","author":[{"given":"Ryohei","family":"Tanigawa","sequence":"first","affiliation":[{"name":"Global Clinical Development Department Kowa Company Ltd.  Chuo\u2010ku Japan"},{"name":"Department of Hepatology, Division of Metabolism Faculty of Medicine Saga University  Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Ueno","sequence":"additional","affiliation":[{"name":"Tohoku Central Hospital for Public School Teachers  Yamagata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2374-2889","authenticated-orcid":false,"given":"Hirokazu","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Hepatology, Division of Metabolism Faculty of Medicine Saga University  Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayumi","family":"Saito","sequence":"additional","affiliation":[{"name":"Global Clinical Development Department Kowa Company Ltd.  Chuo\u2010ku Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Suganami","sequence":"additional","affiliation":[{"name":"Clinical Data Science Department Kowa Company Ltd.  Chuo\u2010ku Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6358-5283","authenticated-orcid":false,"given":"Atsushi","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Medicine School of Medicine Teikyo University  Itabashi\u2010ku Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(24)01303\u20105"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtauto.2023.100188"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2306185"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2312100"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000000557"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.5551\/jat.64112"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2026.01.008"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.5551\/jat.65395"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo13050626"},{"key":"e_1_2_13_11_1","doi-asserted-by":"crossref","unstructured":"G. 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