Ultrastructural characteristics of the respective forms of hepatic stellate cells in chronic hepatitis B as an example of high fibroblastic cell plasticity. The first assessment in children.

PURPOSE

Activation of hepatic stellate cells (HSCs), mainly responsible for extracellular matrix synthesis, is assumed to be central event in the process of liver fibrogenesis. The major objective of the research was to analyze the ultrastructural profile of activated HSCs in children with chronic hepatitis B (chB), with respect to fibrosis intensity.

MATERIALS/METHODS: Ultrastructural investigations of HSCs were conducted on liver bioptates from 70 children with clinicopathologically diagnosed chB before antiviral treatment. Biopsy material, fixed in paraformaldehyde and glutaraldehyde solution, was routinely processed for electron-microscopic analysis.

RESULTS

In children with intensive liver fibrosis (S-2 and S-3), the ultrastructural picture showed almost total replacement of quiescent HSCs (Q-HSCs) by activated, i.e. transitional HSCs (T-HSCs). Among T-HSCs, two types of cells were distinguished: cells exhibiting initiation of HSC activation (Ti-HSCs), never before described in chB, that were frequently accompanied by activated Kupffer cells, and cells with features of perpetuation of activation (Tp-HSCs). Tp-HSCs were elongated and characterized by substantial loss of cytoplasmic lipid material; they contained an increased number of cytoskeletal components, extremely dilated channels of granular endoplasmic reticulum and activated Golgi apparatus, which indicated their marked involvement in intensive synthesis of extracellular matrix proteins. Many collagen fibers were found to adhere directly to Tp-HSCs.

CONCLUSIONS

The current study showed T-HSCs to be an important link between Q-HSCs and myofibroblastic HSCs (Mf-HSCs). Transformation of HSCs into new morphological variations (Ti-HSCs; Tp-HSCs and Mf-HSCs), observed along with growing fibrosis, indicates their high plasticity and a key role in fibrogenesis in pediatric chB.