CLINICAL MORPHOLOGY OF THE LIVER: DISPLASIA, APOPTOSIS, REGENERATION
Abstract
Background. The existing criteria of morphological changes in the liver do not contain descriptions of the consequences of HCV persistence, which simultaneously characterize oncogenic evolution (dysplasia), death (apoptosis) and regeneration (mitosis, amitosis, polyploidy, multinucleosis) of liver cells.
Objective – to present morphological changes in the liver of patients with HCV infection and other lesions that simultaneously characterize the process of dysplasia, apoptosis and regeneration of cellular and extracellular potential.
Material and methods. Liver biopsy samples were obtained by performing a liver aspiration biopsy in patients with chronic hepatitis C (CHC), whose written informed consent had been obtained. Histological sections were stained with hematoxylin and eosin, picrofuxin according to Van Gieson and Masson, for hemosiderin by Perls’ method. Semithin sections (1 мm thick) were successively stained with azure II, the main magenta. Micrographs were obtained using a digital video camera (Leica FC 320, Germany). Electron microscopic preparations were studied in an electron microscope JEM-1011 (JEOL, Japan) at magnifications of 10,000-60,000 with an accelerating voltage of 80 kW. To take pictures, we used an Olympus Mega View III digital camera (Germany) and iTEM image processing software (Olympus, Germany).
Results. Changes in the liver during CHC are simultaneously characterized by poikilocytosis, anisocytosis, hyperchromatosis, anomalies in the mitotic cell cycle, nuclear polymorphism (multiformity), the presence of multinuclear hepatocytes – often gigantic with a large number (up to 15) of hyperchromic nuclei and giant cell multinuclear symplasts, polyploidy and significant changes in intracellular organelles (nuclei and mitochondria.
Conclusions. In CHC, the liver simultaneously realizes a program of neoplastic evolution, apoptosis and regeneration of the cellular potential, which mechanisms, launch and implementation time is individual and requires further study.
References
1. Al'teracija i vnutrikletochnaja regeneracija gepatocitov pri dejstvii RNK-genomnogo virusa gepatita C [Alteration and intracellular regeneration of hepatocytes under the action of RNA genomic Hepatitis C virus] / G. I. Nepomnjashhih [i dr.] // Bjulleten' jeksperimental'noj biologii i mediciny [Bulletin of Experimental Biology and Medicine]. – 1999. – Tom 128, № 7. – S. 583-587. (Russian)
2. Anatskaya, O. V. Genome multiplication as adaptation to tissue survival: evidence from gene expression in mammalian heart and liver / O. V. Anatskaya, A. E. Vinogradov // Genomics. – 2007. – Vol. 89, № 1. – P. 70-80.
3. Anatskaya, O. V. Somatic polyploidy associated metabolic changes revealed by modular biology / O. V. Anatskaya, А. Е. Vinogradov // Tsitologiya. – 2010. – Vol. 52, № 1. – Р. 52-62. (Russian)
4. Aprosina, Z. G. Virusnyj gepatit C [Viral hepatitis C] / Z. G. Aprosina, T. M. Ignatova, P. E. Krel' // Arhiv patologii. – 1994. – № 11. – S. 79-81. (Russian)
5. Arenas, M. J. Apoptosis: mechanism and roles in pathology / M. J. Arenas, A. H. Wyllie // Int. Rev. Exp. Pathol. – 1991. – Vol. 32. – P. 223-254.
6. Aruin, L. I. Apoptoz i patologija pecheni [Apoptosis and pathology of the liver] / L. I. Aruin // Rossijskij zhurnal gastrojenterologii, gepatologii, koloproktologii [Russian Journal of Gastroenterology, Hepatology, Coloproctology]. – 1998. – № 2. – S. 6-17. (Russian)
7. Bueverov, A. O. Immunologicheskie mehanizmy povrezhdenija pecheni [Immunological mechanisms of liver damage] / A. O. Bueverov // Rossijskij zhurnal gastrojenterologii, gepatologii, koloproktologii [Russian Journal of Gastroenterology, Hepatology, Coloproctology]. – 1998. – № 5. – S. 18-20. (Russian)
8. Classification of chronic hepatitis: diagnosis, grading and staging / J. G. Desmet [et al.] // Hepatology. – 1994. – Vol. 19 (6). – P. 1513-1520.
9. Expression of Hepatitis C Virus Proteins Induces Distinct Membrane Alterations Including a Candidate Viral Replication Complex / D. Egger [et al.] // J. Virol. – 2002. – № 76 (12). – Р. 5974-5984.
10. Glauert, A. M. Fixation, degydratation and embedding of biological specimens / A. M. Glauert // Practical Methods in Electron Microscopy / A. M. Glauert [ed.]. – New York : American Elsevier, 1975. – Vol. 3, part 1. – 207 p.
11. Glauert, R. H. Araldite as embedding medium for electron microscopy / R. H. Glauert // J. Biophys. Biochem. Cytol. – 1958. – Vol. 4. – P. 409-414.
12. Hepatitis C virus targets DC-SIGN and L-SIGN to scape Lisosomal degradation / I. Ludwig [et al.] // J. Virol. – 2004. – Vol. 78, № 15. – P. 8322-8332.
13. Induces Binucleation/Polyploidization in Hepatocytes through a Src-Dependent Cytokinesis Failure / M. De Santis Puzzonia [et al.] // PLoS One. – 2016. – Vol. 11 (11). – URL: https://doi.org/10.1371journal.pone.0167158.
14. Ivashkin, V. T. Mehanizmy immunnogo «uskol'zanija» pri virusnyh gepatitah [Immunological mechanisms of liver damage] / V. T. Ivashkin // Rossijskij zhurnal gastrojenterologii, gepatologii, koloproktologii [Russian Journal of Gastroenterology, Hepatology, Coloproctology]. – 2000. – № 5. – S. 7-13. (Russian)
15. Jeong, S. W. C virus and hepatocarcinogenesis / S. W. Jeong, J. Y. Jang, R. T. Chung // Clinical and molecular hepatology. – 2012. – № 18 (4). – Р. 347-356.
16. Klinicheskaja citologija pecheni: zvezdchatye kletki Ito [Clinical cytology of the liver: stellate cells of Ito] / V. M. Tsyrkunov [i dr.] // Zhurnal Grodnenskogo gosudarstvennogo medicinskogo universiteta [Journal of the Grodno State Medical University]. – 2016. – № 4 (56). – S. 90-99. (Russian)
17. Klinicheskij analiz izmenenij ul'trastruktury gepatocitov pacientov hronicheskim gepatitom С [Clinical analysis of changes in the hepatocyte ultrastructure of patients with chronic hepatitis C] / S. P. Lukashik [i dr.] // Infekcionnye bolezni. – 2005. – Tom 3, № 2. – S. 18-21. (Russian)
18. Loginov, A. S. Klinicheskaja morfologija pecheni / A. S. Loginov, L. I. Aruin. – Moskva : Medicina, 1985. – 238 s. (Russian)
19. Magno, G. Apoptosis, oncosias, necrosis / G. Magno, I. Joris // Am. J. Pathol. – 1995. – Vol. 146. – P. 3-15.
Millonig, G. A. Advantages of a phosphate buffer for osmium tetroxide solutions in fixation / G. A. Millonig // J. Appl. Рhysics. – 1961. – Vol. 32. – P. 1637-1643.
21. Mitotic polyploidization of mouse heart myocytes during the first postnatal week / W. Brodsky [et al.] // Cell and Tissue Research. – 1980. – Vol. 210, № 1. – P. 133-144.
22. Obshhaja patologija cheloveka : rukovodstvo dlja vrachej / pod red. A. I. Strukova, V. V. Serova, D. S. Sarkisova : v 2 t. – 2-e izd, pererab. i dop. – Moskva : Medicina, 1990. – Tom 1. – 448 s. (Russian)
23. Patogeneticheskaja rol' zvezdchatyh kletok Ito I kletochnyh kooperacij v formirovanii fibroza pri hronicheskom gepatite C [The pathogenetic role of Ito star cells and cell cooperations in the formation of fibrosis in chronic hepatitis C] / S. P. Lukashik [i dr.] // Infekcionnye bolezni. – 2010. – Tom 8, № 2. – S. 7-12. (Russian)
24. Reynolds, E. S. The use of lead citrate at high pH as an electronopaque stain in electron microscopy / E. S. Reynolds // The Journal of Cell Biology. – 1963. – Vol. 17. – P. 208-212.
25. Sato, T. An electron microscopic study of specimen-fixed for longer periods in phosphate buffered formalin / T. Sato, I. Takagi // J. Electron. Microsc. – 1982. – Vol. 31, № 4. – P. 423-428.
26. Schoenfelder, K. P. The expanding implications of polyploidy / K. P. Schoenfelder, D. T. Fox // The Journal of Cell Biology. – 2015. – № 209 (4). – Р. 485-491.
27. Sherlok, Sh. Zabolevanie pecheni i zhelchnyh putej / Sh. Sherlok, Dzh. Duli. – Moskva : GJeOTAR-Media, 1999. – 859 s.
28. Serov, V. V. Morfologicheskaja diagnostika zabolevanij pecheni / V. V. Serov, K. Lapish. – Moskva : Medicina, 1989. – 336 s. (Russian)
29. Skljar, L. F. Apoptoz i ego vzaimosvjazi s gepatocelljuljarnym povrezhdeniem i nekotorymi pokazateljami lokal'nogo citokinovogo profilja pri hronicheskoj NSV-infekcii [Apoptosis and its relationship with hepatocellular damage and some indicators of local cytokine profile in chronic HCV infection] / L. F. Skljar, E. V. Markelova, P. A. Luk'janov // Medicinskaja immunologija. – 2008. – Tom 10, № 4/5. – S. 415-422. (Russian)
30. The hepatitis C virus nonstructural protein 4B is an integral endoplasmic reticulum membrane protein / Т. Hugle [et al.] // Virology. – 2001. – № 1. – Р. 70-81.
31. The role of liver biopsy in chronic hepatitis C / S. Saaden [et al.] // Hepatology. – 2001. – Vol. 33, № 1. – P. 196-200.
32. Tsyrkunov, V. M. HCV-infekcija : monografija / V. M. Cyrkunov, N. V. Matievskaja, S. P. Lukashik ; pod red. V. M. Tsyrkunova. – Minsk : Asar, 2012. – 480 s. (Russian)
33. Watson, M. L. Staining of tissue sections for electron microscopy with heavy metals / M. L. Watson // J. Biophys. Biochem. Cyt. – 1958. – Vol. 4. – P. 475-478.
