{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:55:49Z","timestamp":1792007749571,"version":"4.4.0"},"reference-count":53,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,5,28]],"date-time":"2014-05-28T00:00:00Z","timestamp":1401235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Non\u2010alcoholic fatty liver disease (<jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content>), a hepatic manifestation of metabolic syndrome, is associated with an increased risk of developing lifestyle\u2010related diseases including type 2 diabetes, cardiovascular disease and cerebral vessel disease. No current drug therapy provides the ideal effects of decreasing hepatic inflammation while simultaneously improving liver fibrosis. Liraglutide is a glucagon\u2010like peptide\u20101 receptor agonist that affects the histological findings in patients with non\u2010alcoholic steatohepatitis (<jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>). This study was conducted to evaluate the effect and action of liraglutide for biopsy\u2010proven <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>After lifestyle modification intervention for 24 weeks, subjects whose hemoglobin <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>1c levels failed to improve to less than 6.0% and\/or whose alanine aminotransferase levels were not lower than baseline, received liraglutide at 0.9\u2009mg\/body per day for 24\u2009weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 27 subjects, 26 completed the lifestyle modification intervention. Nineteen subjects received liraglutide therapy for 24\u2009weeks. Body mass index, visceral fat accumulation, aminotransferases and glucose abnormalities improved significantly. Repeated liver biopsy was performed in 10 subjects who continued liraglutide therapy for 96 weeks. Six subjects showed decreased histological inflammation as determined by <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content> activity score and stage determined by <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>runt classification. We saw no significant adverse events during therapy with liraglutide.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our pilot study demonstrated that treatment with liraglutide had a good safety profile and significantly improved liver function and histological features in <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content> patients with glucose intolerance.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.12351","type":"journal-article","created":{"date-parts":[[2014,5,5]],"date-time":"2014-05-05T02:11:00Z","timestamp":1399255860000},"page":"269-278","source":"Crossref","is-referenced-by-count":170,"title":["Pilot study of liraglutide effects in non\u2010alcoholic steatohepatitis and non\u2010alcoholic fatty liver disease with glucose intolerance in <scp>J<\/scp>apanese patients (<scp>LEAN<\/scp>\u2010<scp>J<\/scp>)"],"prefix":"10.1111","volume":"45","author":[{"given":"Yuichiro","family":"Eguchi","sequence":"first","affiliation":[{"name":"Division of Hepatology Saga Medical School  Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichiro","family":"Kitajima","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Saga Medical School  Saga Japan"},{"name":"Clinical Gastroenterology Eguchi Hospital  Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyuki","family":"Hyogo","sequence":"additional","affiliation":[{"name":"Department of Medicine and Molecular Science Graduate School of Biomedical Sciences Hiroshima University  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Saga Medical School  Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoyasu","family":"Kojima","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Saga Medical School  Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Kochi Medical School  Kochi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norimasa","family":"Araki","sequence":"additional","affiliation":[{"name":"Clinical Gastroenterology Eguchi Hospital  Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Clinical Gastroenterology Eguchi Hospital  Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyuki","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Saga Medical School  Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yayoi","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Saga Medical School  Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Ide","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Saga Medical School  Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiga","family":"Otsuka","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Saga Medical School  Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwata","family":"Ozaki","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Saga Medical School  Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naofumi","family":"Ono","sequence":"additional","affiliation":[{"name":"Clinical Gastroenterology Eguchi Hospital  Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahisa","family":"Eguchi","sequence":"additional","affiliation":[{"name":"Clinical Gastroenterology Eguchi Hospital  Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keizo","family":"Anzai","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Saga Medical School  Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Japan Study Group for NAFLD (JSG\u2010NAFLD)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,5,28]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra011775"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50193"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23276"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-789X.2009.00657.x"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-009-0115-x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.01.004"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2012.06491.x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2013.06.009"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1185\/03007995.2013.837817"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2011.12.015"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-1241.2010.02498.x"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60659-0"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61246-5"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.2009.02666.x"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc08-1355"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-009-1472-y"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc08-2124"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.12149"},{"key":"e_1_2_6_20_1","article-title":"Glucagon like peptide\u20101 analogue, liraglutide, improves liver fibrosis markers in obese women with polycystic ovary syndrome and non\u2010alcoholic fatty liver disease","author":"Kahal H","year":"2013","journal-title":"Clin Endocrinol (Oxf)"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0050117"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1100\/2012\/496453"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000441-199203000-00002"},{"key":"e_1_2_6_24_1","unstructured":"Ministry of Health Labour and Welfare of Japan.Exercise and physical activity reference for health promotion.2006. Available at:http:\/\/www.nih.go.jp\/eiken\/programs\/pdf\/epar2006.pdf. Accessed July 2006."},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.19.10.1138"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.211.1.r99ap15283"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70506-8"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.1999.01377.x"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20701"},{"key":"e_1_2_6_31_1","first-page":"1313","article-title":"Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"45","author":"Brunt EM","year":"2005","journal-title":"Hepatology"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2004.09.012"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2009.03.019"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2008.08.006"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc08-1797"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60307-8"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116186"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/35041046"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108378200"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.09.032"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00274.2011"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2011.02462.x"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23569"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21006"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2013.2720"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.02.018"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199305203282001"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2013.3374"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472\u20106823\u201010\u201020"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69705-5"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-0115"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.2337\/db10-1338"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1159\/000341510"},{"key":"e_1_2_6_54_1","first-page":"240","article-title":"Effects of sitagliptin in diabetic patients with nonalcoholic steatohepatitis","volume":"75","author":"Yilmaz Y","year":"2012","journal-title":"Acta Gastroenterol Belg"}],"container-title":["Hepatology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhepr.12351","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hepr.12351","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T04:22:07Z","timestamp":1696306927000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hepr.12351"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,28]]},"references-count":53,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,3]]}},"alternative-id":["10.1111\/hepr.12351"],"URL":"https:\/\/doi.org\/10.1111\/hepr.12351","archive":["Portico"],"relation":{},"ISSN":["1386-6346","1872-034X"],"issn-type":[{"value":"1386-6346","type":"print"},{"value":"1872-034X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,28]]}}}