LYSOSOME-DEPENDENT DEATH OF HEPATOCYTES IN CHRONIC HEPATITIS C
Abstract
Background. Currently, lysosome-dependent cell death (LDCD) is universally recognized and directly correlated with many mechanisms of hepatocyte apoptosis in chronic hepatitis C (CHC). In the domestic literature there is a shortage of visualization materials of this process in chronic hepatitis C. Objective – to present the morphological characteristics of lysosome-dependent hepatocyte cell death. Material and methods. The object of the study was intravital liver biopsy samples of 18 patients with chronic HCV infection, obtained after they had signed informed consent. Liver biopsies were studied in a JEM-1011 electron microscope (JEOL, Japan) at magnifications of 10,000 - 60,000 at accelerating voltage of 80 kW. To obtain images, we used an Olympus Mega View III digital camera with iTEM image processing software (Olympus, Germany). Results. The illustrations and description show the interrelated sequential stages of lysosome-dependent cell death (LDCD) and autophagy-dependent cell death (ADCD) of hepatocytes in chronic hepatitis C. The process of autophagosome formation is presented, three types of autophagy are described (macroautophagy, microautophagy, chaperone-mediated autophagy). One of the main forms of autophagy, mitophagy, is illustrated in detail. The features of autophagy, its proviral and antiviral mechanisms, as well as the role of HCV in apoptosis associated with autophagy, are described. Conclusions. Autophagy-dependent hepatocyte death in chronic hepatitis C is a highly regulated and conservative cellular mechanism for maintaining cell homeostasis and promoting cell survival. HCV-induced autophagy suppresses apoptosis to promote cell survival. The autophagic response caused by HCV reduces the antiviral innate immune response in HCV infected hepatocytes, contributing to the chronicity of the infectious process. Visualization of the autophagy process allows for a more accurate assessment of the mechanisms and ultrastructural components of various types and stages of autophagy. Changes in all structural components of autophagy are not isolated, being characterized by a complex of specific signs associated with each other and united by the apoptosogenic mechanism of the pathogenesis of HCV infection.References
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