title: Abnormality of autophagic function and cathepsin expression in the liver from patients with non-alcoholic fatty liver disease.
abstract: OBJECTIVE
  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-alcoholic fatty liver disease (NAFLD).
  
  
  METHODS
  Liver biopsy specimens were obtained from patients with chronic liver diseases (chronic hepatitis C [CHC; n = 20], chronic hepatitis B [CHB; n = 16], primary biliary cirrhosis [PBC; n = 23], NAFLD [n = 22] and control [n = 14]). The number of autophagic vesicles in hepatocytes was counted by using transmission electron microscopy. Expression of cathepsin B, D, L and p62 in the liver section was analyzed by immunohistochemical staining. The histological severity of NAFLD is assessed by NAFLD activity score (NAS).
  
  
  RESULTS
  The number of autophagic vesicles in hepatocytes was significantly increased in both CHC and NAFLD groups, but not CHB and PBC, more than control. Although hepatocytes with aggregation of p62 were observed in less than 15% of CHC, p62 aggregation was detected in approximately 65% of NAFLD. Cathepsin B, D and L expression was significantly suppressed in the liver from NAFLD patients. Suppression of cathepsin B, D and L expression was not observed in CHB, CHC and PBC. In NAFLD patients, p62 aggregation was correlated with serum alanine aminotransferase value and inflammatory activity by NAS.
  
  
  CONCLUSIONS
  These results indicate that a decrease in hepatic cathepsin expression in NAFLD is associated with autophagic dysfunction. Hepatic inflammation correlates with autophagic dysfunction in NAFLD. These findings indicate that the suppression of autophagic proteolysis by hepatic steatosis is involved in the pathogenesis of NAFLD.
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Fukuo
authors.forename: Shunhei
authors.initials: S
authors.lastname: Yamashina
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sonoue
authors.forename: Atsushi
authors.initials: A
authors.lastname: Arakawa
authors.forename: Eisuke
authors.initials: E
authors.lastname: Nakadera
authors.forename: Tomonori
authors.initials: T
authors.lastname: Aoyama
authors.forename: Akira
authors.initials: A
authors.lastname: Uchiyama
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kon
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ikejima
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe
keywords: autophagy; inflammation; p62; steatosis