Electron microscopic alterations in intermediate hepatocyte-like cells in children with chronic hepatitis B: the first report in pediatric patients

Abstract

The study objective was an in-depth ultrastructural analysis of intermediate hepatocyte-like cells (IHCs), constituting a subpopulation of liver progenitor/oval cells, in children with chronic hepatitis B viral (HBV) infection. Ultrastructural investigations were conducted on liver biopsy material, fixed in a solution of 2.5% glutaraldehyde, 2% paraformaldehyde, and 0.1 mol/l cacodylate buffer, obtained from 40 children, aged 3-16 years, with chronic hepatitis B. Transmission-electron microscopic analysis of liver progenitor/oval cells showed, apart from a morphologically unchanged population of oval cells, the presence of IHCs displaying variously pronounced ultrastructural changes, including degeneration. Interesting was that damaged IHCs were mainly observed in patients with a coexisting advanced liver fibrosis, where they frequently adhered to bundles of collagen fibers. Submicroscopic abnormalities in these cells referred mainly to mitochondria and granular endoplasmic reticulum. The most pronounced mitochondrial alterations observed in degenerating IHCs in the course of chronic HBV infection were characterized by distinct swelling, loss of mitochondrial crests, and the presence of myelin structures within the matrix. In granular endoplasmic reticulum, shortening and segmental degranulation of the reticulum were observed. The above changes were accompanied by the appearance of primitive phagosome-like structures with absorbed biliary pigment. In the vicinity of altered IHCs, transitional hepatic stellate cells could be found. Our study seems to suggest that chronic HBV infection, lasting from childhood and coexisting with intensive fibrosis may, with the involvement of other carcinogenic factors, promote degenerating IHCs towards neoplastic transformation in adulthood.