Hepatocellular ballooning in NASH

JOURNAL OF HEPATOLOGY

卷:53

Article

Caldwell, Stephen¹  Ikura, Yoshihiro²  Dias, Daniela^1,3  Isomoto, Kosuke²  Yabu, Akito²  Moskaluk, Christopher⁴  Pramoonjago, Patcharin⁴  Simmons, Winsor^1,5  Scruggs, Harriet⁴  Rosenbaum, Nicholas⁴  Toms, Patsy⁴  Argo, Curtis K.¹  Al-Osaimi, Abdullah M. S.¹  Redick, Jan A.⁶ 

[1] Univ Virginia, GI Hepatol, Charlottesville, VA USA

[2] Osaka City Univ, Dept Pathol, Osaka 558, Japan

[3] Univ Fed Bahia, Salvador, BA, Brazil

[4] Univ Virginia, Dept Pathol, Charlottesville, VA 22903 USA

[5] Univ Virginia, Surg Therapeut Advancement Ctr, Charlottesville, VA USA

[6] Univ Virginia, Adv Microscopy Facil, Charlottesville, VA USA

关键词: Cellular ballooning;    Steatohepatitis;    NASH;    NAFLD;    Keratin 18;    Fat staining;    Oil red O;   

DOI  :  10.1016/j.jhep.2010.04.031

来源: Elsevier

【 摘 要 】

Background & Aims: Hepatocellular ballooning is a key finding in nonalcoholic steatohepatitis (NASH). It is conventionally defined by hemotoxylin and eosin (H&E) staining showing enlarged cells with rarefied cytoplasm and recently by changes in the cytoskeleton. Fat droplets are emerging as important organelles in cell metabolism. To address a possible relation between fat droplets and ballooning, we studied fat staining, H&E, and keratin 18 staining in human NASH. Methods: Sequential staining and high resolution imaging were used to study freshly prepared cryo-sections from 10 patients with histologically confirmed steatohepatitis using oil red O for fat droplet identification, H&E to identify ballooning, and anti-K18 to confirm cytoskeletal changes. High resolution images were captured at each stage using the Aperio Scanscope. To provide ultrastructural correlation, glutaraldehyde-fixed specimens were studied using transmission electron microscopy (TEM) with serial sectioning for localization of ballooned cells by light microscopy and TEM in identical specimens. Results: Serial staining consistently demonstrated that hepatocellular ballooning is associated with fat droplet accumulation evident by oil red O positivity and depletion of cytoplasmic keratin 18 with K-18 positive Mallory-Denk bodies (MDB). TEM confirmed the association between osmium stained fat droplets, MDB formation, and cellular enlargement and suggested droplet-associated dilation of the endoplasmic reticulum. Conclusions: These results indicate a relationship between cellular ballooning, fat droplet accumulation, and cytoskeletal injury in NASH. We speculate that injury to multiple organelles, including fat droplets and endoplasmic reticulum, contribute to this characteristic finding. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

【 授权许可】

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