Hepatocellular ballooning in liver cirrhosis is due to glycogenotic metabolic aberrations with facultative steatosis and ground glass formation

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.

Publikationsverlauf

Artikel online veröffentlicht:
26. Januar 2022