{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:42:46Z","timestamp":1791387766862,"version":"4.3.3"},"reference-count":35,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,2,17]],"date-time":"2014-02-17T00:00:00Z","timestamp":1392595200000},"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":[[2014,9]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Recent evidences indicate that hepatic steatosis suppresses autophagic proteolysis. The present study evaluated the correlation between autophagic function and cathepsin expression in the liver from patients with non\u2010alcoholic fatty liver disease (<jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Liver biopsy specimens were obtained from patients with chronic liver diseases (chronic hepatitis <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content> [<jats:styled-content style=\"fixed-case\">CHC<\/jats:styled-content>; <jats:italic>n<\/jats:italic>\u2009=\u200920], chronic hepatitis <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> [<jats:styled-content style=\"fixed-case\">CHB<\/jats:styled-content>; <jats:italic>n<\/jats:italic>\u2009=\u200916], primary biliary cirrhosis [<jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content>; <jats:italic>n<\/jats:italic>\u2009=\u200923], <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content> [<jats:italic>n<\/jats:italic>\u2009=\u200922] and control [<jats:italic>n<\/jats:italic>\u2009=\u200914]). The number of autophagic vesicles in hepatocytes was counted by using transmission electron microscopy. Expression of cathepsin <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content> and p62 in the liver section was analyzed by immunohistochemical staining. The histological severity of <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content> is assessed by <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content> activity score (<jats:styled-content style=\"fixed-case\">NAS<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The number of autophagic vesicles in hepatocytes was significantly increased in both <jats:styled-content style=\"fixed-case\">CHC<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content> groups, but not <jats:styled-content style=\"fixed-case\">CHB<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content>, more than control. Although hepatocytes with aggregation of p62 were observed in less than 15% of <jats:styled-content style=\"fixed-case\">CHC<\/jats:styled-content>, p62 aggregation was detected in approximately 65% of <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content>. Cathepsin <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content> expression was significantly suppressed in the liver from <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content> patients. Suppression of cathepsin <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content> expression was not observed in <jats:styled-content style=\"fixed-case\">CHB<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">CHC<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content>. In <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content> patients, p62 aggregation was correlated with serum alanine aminotransferase value and inflammatory activity by <jats:styled-content style=\"fixed-case\">NAS<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results indicate that a decrease in hepatic cathepsin expression in <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content> is associated with autophagic dysfunction. Hepatic inflammation correlates with autophagic dysfunction in <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content>. These findings indicate that the suppression of autophagic proteolysis by hepatic steatosis is involved in the pathogenesis of <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.12282","type":"journal-article","created":{"date-parts":[[2013,12,3]],"date-time":"2013-12-03T02:15:03Z","timestamp":1386036903000},"page":"1026-1036","source":"Crossref","is-referenced-by-count":174,"title":["Abnormality of autophagic function and cathepsin expression in the liver from patients with non\u2010alcoholic fatty liver disease"],"prefix":"10.1111","volume":"44","author":[{"given":"Yuka","family":"Fukuo","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Juntendo University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunhei","family":"Yamashina","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Juntendo University School of Medicine 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