{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T15:40:15Z","timestamp":1792856415423,"version":"4.5.0"},"reference-count":31,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T00:00:00Z","timestamp":1631750400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015993","name":"Kowa Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015993","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":[[2021,11]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pemafibrate is a novel, selective peroxisome proliferator\u2010activated receptor \u03b1 modulator (SPPARM\u03b1). In mice, Pemafibrate improved the histological features of non\u2010alcoholic steatohepatitis (NASH). In patients with dyslipidaemia, it improved serum alanine aminotransferase (ALT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To evaluate the efficacy and safety of Pemafibrate in patients with high\u2010risk, non\u2010alcoholic fatty liver disease (NAFLD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This double\u2010blind, placebo\u2010controlled, randomised multicentre, phase 2 trial randomised 118 patients (1:1) to either 0.2\u00a0mg Pemafibrate or placebo, orally, twice daily for 72\u00a0weeks. The key inclusion criteria included liver fat content of \u226510% by magnetic resonance imaging\u2010estimated proton density fat fraction (MRI\u2010PDFF); liver stiffness of \u22652.5\u00a0kPa, by magnetic resonance elastography (MRE); and elevated ALT levels. The primary endpoint was the percentage change in MRI\u2010PDFF from baseline to week 24. The secondary endpoints included MRE\u2010based liver stiffness, ALT, serum liver fibrosis markers and lipid parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      There was no significant difference between the groups in the primary endpoint (\u22125.3% vs \u22124.2%; treatment difference \u22121.0%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.85). However, MRE\u2010based liver stiffness significantly decreased compared to placebo at week 48 (treatment difference \u22125.7%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.036), and was maintained at week 72 (treatment difference \u22126.2%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.024), with significant reduction in ALT and LDL\u2010C. Adverse events were comparable between the treatment groups and therapy was well tolerated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Pemafibrate did not decrease liver fat content but had significant reduction in MRE\u2010based liver stiffness. Pemafibrate may be a promising therapeutic agent for NAFLD\/NASH, and also be a candidate for combination therapy with agents that reduce liver fat content. ClinicalTrials.gov, number: NCT03350165.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apt.16596","type":"journal-article","created":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T07:02:08Z","timestamp":1631775728000},"page":"1263-1277","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":203,"title":["Randomised clinical trial: Pemafibrate, a novel selective peroxisome proliferator\u2010activated receptor \u03b1 modulator (SPPARM\u03b1), versus placebo in patients with non\u2010alcoholic fatty liver disease"],"prefix":"10.1111","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6263-1436","authenticated-orcid":false,"given":"Atsushi","family":"Nakajima","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Yokohama City University Graduate School of Medicine  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4693-5736","authenticated-orcid":false,"given":"Yuichiro","family":"Eguchi","sequence":"additional","affiliation":[{"name":"Loco Medical General Institute  Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7815-549X","authenticated-orcid":false,"given":"Masato","family":"Yoneda","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Yokohama City University Graduate School of Medicine  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1931-6326","authenticated-orcid":false,"given":"Kento","family":"Imajo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Yokohama City University Graduate School of Medicine  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4634-6616","authenticated-orcid":false,"given":"Nobuharu","family":"Tamaki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Musashino Red Cross Hospital  Tokyo Japan"},{"name":"NAFLD Research Center Division of Gastroenterology Department of Medicine University of California San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Suganami","sequence":"additional","affiliation":[{"name":"Clinical Data Science Department Kowa Company Ltd  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Nojima","sequence":"additional","affiliation":[{"name":"Clinical Data Science Department Kowa Company Ltd  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryohei","family":"Tanigawa","sequence":"additional","affiliation":[{"name":"Clinical Development Department Kowa Company Ltd  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakazu","family":"Iizuka","sequence":"additional","affiliation":[{"name":"Clinical Development Department Kowa Company Ltd  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Iida","sequence":"additional","affiliation":[{"name":"Clinical Development Department Kowa Company Ltd  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4845-9991","authenticated-orcid":false,"given":"Rohit","family":"Loomba","sequence":"additional","affiliation":[{"name":"NAFLD Research Center Division of Gastroenterology Department of Medicine University of California San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25762"},{"key":"e_1_2_8_3_1","volume-title":"NICE Guideline","author":"National Guideline Centre","year":"2016"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28431"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.09.021"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-017-1415-1"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-020-0823-5"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.02.019"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-017-0602-y"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.10.039"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42477"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.06.005"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2018.05.059"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756283X16656735"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(17)31811-1"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30974"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31785-9"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-64902-8"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.12845"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu7115475"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.11.048"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.09.024"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-46172-1"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27368"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.01.038"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30474-4"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.07.027"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.113.301468"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2016.03.003"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2018.06.010"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-323082"},{"issue":"20","key":"e_1_2_8_32_1","first-page":"31220","article-title":"Change in MRI\u2010PDFF and histologic response in patients with nonalcoholic steatohepatitis: a systematic review and meta\u2010analysis","volume":"1542","author":"Stine JG","year":"2020","journal-title":"Clin Gastroenterol Hepatol"}],"container-title":["Alimentary Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apt.16596","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/apt.16596","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apt.16596","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T02:50:15Z","timestamp":1693277415000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apt.16596"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,16]]},"references-count":31,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["10.1111\/apt.16596"],"URL":"https:\/\/doi.org\/10.1111\/apt.16596","archive":["Portico"],"relation":{},"ISSN":["0269-2813","1365-2036"],"issn-type":[{"value":"0269-2813","type":"print"},{"value":"1365-2036","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,16]]},"assertion":[{"value":"2021-06-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}