| dc.description.abstract | 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. | |
