Background and aim Hepatocellular ballooning frequently occurs in chronic
liver diseases, particularly alcoholic and non-alcoholic steatohepatitis, often
associated with Mallory-Denk body and ground glass formation. Cytoplasmic
enlargement and “rarefication” due to ill-defined degenerative
changes have been related to these alterations, but their striking resemblance to
glycogenotic/steatotic changes characterizing preneoplastic clear cell
populations discovered and detailed in various animal models of hepatocarcinogenesis
and chronic human liver diseases prone to develop hepatocellular carcinomas remained
unrecognized.
Materials and methods Using specimens from 96 cirrhotic human livers we
quantified the appearance of ballooned hepatocytes (BH), and studied their
glycogen/lipid stores, Mallory–Denk-bodies, and ground glass
features by light and electron microscopy. Enzyme activities and/or
expression of proteins involved in glycolysis, lipogenesis and proto-oncogenic
signaling cascades were investigated by cytochemical approaches in serial paraffin
and cryostat sections.
Results BH were found in 43.8% of cirrhotic livers with a mean volume
fraction of 14%. Regardless of the underlying etiology, ballooning was
mostly associated with excessive storage of glycogen and/or fat, decreased
glucose-6-phosphatase activity, and increased activity or protein expression of
enzymes involved in glycolysis, lipogenesis and AKT/mTOR pathway.
Conclusion BH often appear in cirrhotic livers, irrespective of the underlying
etiology, mostly showing excessive storage of glycogen and/or lipids.
Ballooning is due to metabolic aberrations corresponding to those of preneoplastic
glycogenotic/steatotic hepatocellular lesions well known from experimental
hepatocarcinogenesis and chronic human liver diseases prone to develop
hepatocellular carcinomas.
