Clinical and Immunomorphological Features of Liver Damage in Severe Preeclampsia

Cover Page
Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access


Background. Liver diseases associated with pregnancy are recorded in 0.7–3% of pregnant women, often accompanied by the development of hepatic dysfunction/insufficiency, and are the cause of increased morbidity and mortality in both mother and child. A pathomorphological study helps to understand the pathophysiology of severe liver damage in preeclampsia, and to optimize the management of such patients. Aims — to study the clinical, morphological and immunohistochemical features of liver tissue lesions in the most severe forms of preeclampsia and eclampsia, which ended in death. Methods. Autopsy material analysis of 10 patients who died from preeclampsia, eclampsia and their complications (main group) and 3 patients who died from other causes (comparison group). Pathomorphological and immunohistochemical studies of organs and tissues (in particular, liver tissue) were performed using a marker of neurons and neuroendocrine cells γ-NSE and a marker of endotheliocytes CD-34. Results. An immunohistochemical study with a CD-34 endotheliocyte marker in the main group revealed a vascularization deficiency in the 2nd and 3rd zone of hepatic acini, there were also foci of necrosis. Such changes indicate deep and prolonged hypoperfusion. The use of the NSE marker in the group of patients who died from preeclampsia/eclampsia revealed a sharp increase in Kupffer cells in the first and second zones of acini with pronounced immunoexpression of NSE in the nuclei and cytoplasm of these cells, which indicates severe hepatic dysfunction (in particular, impaired detoxification and elimination functions of the liver). At the same time, only 3 out of 10 women in the main group are clinically registered with HELLP syndrome, while the rest had signs of multiple organ (including acute liver) failure. Conclusions. The clinical symptoms of liver damage, including those with severe preeclampsia, arise, as a rule, already against the background of severe morphological changes in its tissue and, as a rule, indicate functional decompensation. Liver immunology remains little studied, which requires further research on this problem.

Full Text

Restricted Access

About the authors

Iraida S. Sidorova

I.M. Sechenov First Moscow State Medical University (Sechenov University)

ORCID iD: 0000-0003-2209-8662
SPIN-code: 3823-8259

Russian Federation, Moscow

MD, PhD, Professor, Academician of the RAS

Natalya A. Nikitina

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Author for correspondence.
ORCID iD: 0000-0001-8659-9963
SPIN-code: 8344-1517

Russian Federation, Moscow

MD, PhD, Professor

Mikhail B. Ageev

I.M. Sechenov First Moscow State Medical University (Sechenov University)

ORCID iD: 0000-0002-6603-804X
SPIN-code: 3122-7420

Russian Federation, Moscow


Albert A. Kokin

I.M. Sechenov First Moscow State Medical University (Sechenov University)

ORCID iD: 0000-0001-7615-4530

Russian Federation, Moscow

MD, Resuscitator


  1. Ma K, Berger D, Reau N. Liver Diseases During Pregnancy. Clin Liver Dis. 2019;23(2):345–361. doi:
  2. Westbrook RH, Dusheiko G, Williamson C. Pregnancy and liver disease. Journal of Hepatology. 2016;64(4):933–945. doi:
  3. Филиппов О.С., Гусева Е.В., Малышкина А.И., и др. Материнская смертность в Российской Федерации в 2018 году. Методическое письмо Министерства здравоохранения Российской Федерации от 18.09.2019 № 15-4/10/2-8714. — 100 с. [Filippov OS, Guseva EV, Malyshkina AI, et al. Maternal mortality in the Russian Federation in 2018. Metodicheskoe pis’mo Ministerstva zdravookhraneniya Rossiiskoi Federatsii ot 18.09.2018 № 15-4/10/2-8714. 100 p. (in Russ.)]
  4. Kozic JR, Benton SJ, Hutcheon JA, et al. Abnormal liver function tests as predictors of adverse maternal outcomes in women with preeclampsia. J Obstet Gynaecol Can. 2011;33(10):995–1004. doi:
  5. Goel A, Jamwal KD, Ramachandran A, et al. Pregnancy-related liver disorders. J Clin Exp Hepatol. 2014;4(2):151–162. doi:
  6. Natarajan SK, Thangaraj KR, Eapen CE. Liver injury in acute fatty liver of pregnancy: possible link to placental mitochondrial dysfunction and oxidative stress. Hepatology. 2010;51(1):191–200. doi:
  7. Browning MF, Levy HL, Wilkins-Haug LE, et al. Fetal fatty acid oxidation defects and maternal liver disease in pregnancy. Obstet Gynecol. 2006;107(1):115–120. doi:
  8. Gupta M, Feinberg BB, Burwick RM. Thrombotic microangiopathies of pregnancy: Differential diagnosis. Pregnancy Hypertens. 2018;12:29–34. doi:
  9. Gupta M, Govindappagari S, Burwick RM. Pregnancy-Associated Atypical Hemolytic Uremic Syndrome: A Systematic Review. Obstet Gynecol. 2020;135(1):46–58. doi:
  10. Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017;129(21):2836–2846. doi:
  11. Bruel A, Kavanagh D, Noris M, et al. Hemolytic uremic syndrome in pregnancy and post-partum. Clin J Am Soc Nephrol. 2017;12(8):1237–1247. doi:
  12. Козловская Н.Л., Галстян Г.М., Степанюк В.Н. Сложные вопросы диагностики атипичного гемолитико-уремического синдрома в отделении реанимации и интенсивной терапии // Вестник анестезиологии и реаниматологии. — 2019. — Т. 16. – № 4. — С. 65–76. [Kozlovskaya NL, Galstyan GM, Stepanyuk VN. Difficult issues in diagnosing atypical hemolytic-uremic syndrome in the intensive care unit. Bulletin of anesthesiology and resuscitation. 2019;16(4):65–76 (In Russ.)] doi:
  13. Bremer L, Schramm C, Tiegs G. Immunology of hepatic diseases during pregnancy. Semin Immunopathol. 2016;38(6):669–685. doi:
  14. Mikhaleva LM, Gracheva NA, Biryukov AE. The clinical and anatomical aspects of preeclampsia: current features of its course. Arkh Patol. 2018;80(2):11–17. doi:
  15. Thomson AW, Knolle PA. Antigen-presenting cell function in the tolerogenic liver environment. Nat Rev Immunol. 2010;10(11):753–766. doi:
  16. Mehrfeld C, Zenner S, Kornek M, Lukacs-Kornek V. The Contribution of Non-Professional Antigen-Presenting Cells to Immunity and Tolerance in the Liver. Front Immunol. 2018;9:635. doi:
  17. Amiot L, Vu N, Samson M. Biology of the immunomodulatory molecule HLA-G in human liver diseases. J Hepatol. 2015;62(6):1430–1437. doi:
  18. Ferreira LMR, Meissner TB, Tilburgs T, Strominger JL. HLA-G: At the Interface of Maternal-Fetal Tolerance. Trends Immunol. 2017;38(4):272–286. doi:
  19. Чехонин В.П., Гурина О.И., Дмитриева Т.Б. Моноклональные антитела к нейроспецифическим белкам. — М.: Медицина, 2007. — 344 с. [Chekhonin VP, Gurina OI, Dmitriyeva TB. Monoclonal antibodies to neurospecific proteins. Moscow: Medicine; 2007. 344 p. (In Russ.)]
  20. Isgrò MA, Bottoni P, Scatena R. Neuron-Specific Enolase as a Biomarker: Biochemical and Clinical Aspects. Adv Exp Med Biol. 2015;867:125–143. doi:
  21. Thelin EP, Zeiler FA, Ercole A, et al. Serial Sampling of Serum Protein Biomarkers for Monitoring Human Traumatic Brain Injury Dynamics: A Systematic Review. Front Neurol. 2017;8:300. doi:
  22. Зорников Д.Л., Литусов Н.В., Новоселов А.В. Иммунопатология. — Екатеринбург: Изд-во УГМУ, 2017. — 35 с. [Zornikov DL, Litusov NV, Novoselov AV. Immunopathology. Yekaterinburg: Izdatel’stvo UGMU; 2017. 35 p. (In Russ.)]

Supplementary files

Supplementary Files Action
Figure: 1. Comparison group: A - the presence of hypertrophied binuclear hepatocytes (arrows) in the periportal region (acinus zone 1) (pathological examination, staining with hematoxylin and eosin, × 100); B - branched capillary network (arrows) in zone 1 and partly in zone 2 of acini (immunohistochemical study with the marker CD-34, × 50)

Download (900KB) Indexing metadata
Figure: 2. Eclampsia - the main group: total necrosis of hepatocytes and focal hemorrhages (arrows) in three zones of the hepatic acinus (pathological examination, staining with hematoxylin and eosin, × 50)

Download (562KB) Indexing metadata
Figure: 3. Preeclampsia - main group: A - rarefaction of the capillary network (arrows) in zones 1 and 2 of the hepatic acinus (immunohistochemical study, marker CD-34, × 100); B - pronounced immunoexpression of NSE in the nuclei and cytoplasm of hepatic macrophages (Kupffer's cells) against the background of hypertrophied hepatocyte nuclei (immunohistochemical study, NSE marker, × 400)

Download (917KB) Indexing metadata



Abstract - 101

PDF (Russian) - 1


Article Metrics

Metrics Loading ...



Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies