The state of the cytokine profile in pregnant women with non-alcoholic fatty liver disease at the stage of non-alcoholic steatohepatitis with varying degrees of comorbid obesity under the influence of the developed complex therapy program

Authors

DOI:

https://doi.org/10.14739/2310-1210.2023.2.268274

Keywords:

non-alcoholic steatohepatitis, cytokine profile, obesity, pregnancy complications, vitamin E, ursodeoxycholic acid

Abstract

The aim of the study: to evaluate the cytokine profile state in pregnant women with non-alcoholic fatty liver disease (NAFLD) at the stage of non-alcoholic steatohepatitis (NASH) with varying degrees of obesity under the influence of the developed complex therapy program.

Material and methods. We examined 197 pregnant women with NAFLD at the stage of NASH in combination with obesity. The main group I consisted of 98 pregnant women with NAFLD at the stage of NASH with varying degrees of obesity, who were divided into 3 subgroups depending on body mass index (BMI). Among them, 26 pregnant women with BMI of 25.0–29.9 kg/m2 were included in IA group, 48 pregnant women with BMI of 30.0–34.9 kg/m2 were included in IB group, and 24 pregnant women with BMI of 35.0–39.9 kg/m2 – in IC group. All pregnant women in the main group were prescribed complex therapy including vitamin E at a dose of 400 IU/day, ursodeoxycholic acid (UDCA) at a dose of 15 mg/kg/day, and L-carnitine at a dose of 3 g per day. The comparison group consisted of 69 women with NAFLD at the stage of NASH and abdominal obesity, who corresponded to subgroups of the main group (IIA – 23 patients, IIB – 25 women, IIC – 21 pregnant women) and received basic therapy. The control group consisted of 30 healthy women. To evaluate the cytokine profile, levels of IL-1β, IL-6, IL-10 and TNF-α were determined by ELISPOT.

Results. Analysis of the cytokine profile in women with NASH and obesity showed the presence of systemic inflammation links in the examined groups, which was manifested by increased levels of pro-inflammatory and decreased levels of anti-inflammatory interleukins in blood serum of pregnant women. A prescription of the complex treatment contributed to a decreased activity of the inflammatory response, which was manifested by an improvement in the levels of cytokine profile indicators.

Conclusions. NASH during pregnancy is accompanied by significant changes in the cytokine profile. The prescription of complex therapy in the form of vitamin E, UDCA and L-carnitine is effective in the treatment of pregnant women with NAFLD at the stage of NASH due to cumulative and potentiating effects, reducing manifestations of systemic inflammation by normalizing the level of cytokines.

Author Biographies

L. V. Bahnii, I. Horbachevsky Ternopil National Medical University of Health Ministry of Ukraine

MD, Assistant of the Department of Obstetrics and Gynecology 2

S. M. Heriak, Ivan Horbachevsky Ternopil National Medical University of the Ministry of Health of Ukraine

MD, PhD, DSc, Professor, Head of the Department of Obstetrics and Gynecology 2

N. I. Bahnii, Ivan Horbachevsky Ternopil National Medical University of the Ministry of Health of Ukraine

MD, PhD, Associate Professor, Department of Obstetrics and Gynecology 2

References

  1. EASL–EASD–Easo Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. (2016). Journal of Hepatology, 64(6), 1388-1402. https://doi.org/10.1016/j.jhep.2015.11.004
  2. Cabinet of Ministers of Ukraine. (2018, July 26). Pro zatverdzhennia ta vprovadzhennia medyko-tekhnolohichnykh dokumentiv zi standartyzatsii medychnoi dopomohy pry khronichnykh neinfektsiinykh hepatytakh [On approval and implementation of medical and technological documents standardizing medical care of chronicnon-infectious hepatitis (No. 530-p)]. [in Ukrainian] https://zakon.rada.gov.ua/laws/show/530-2018-%D1%80#top
  3. Francque, S. M., Marchesini, G., Kautz, A., Walmsley, M., Dorner, R., Lazarus, J. V., Zelber-Sagi, S., Hallsworth, K., Busetto, L., Frühbeck, G., Dicker, D., Woodward, E., Korenjak, M., Willemse, J., Koek, G. H., Vinker, S., Ungan, M., Mendive, J. M., & Lionis, C. (2021). Non-alcoholic fatty liver disease: A patient guideline. JHEP Reports, 3(5), 100322. https://doi.org/10.1016/j.jhepr.2021.100322
  4. Younossi, Z. M. (2018). Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: Implications for Liver Transplantation. Liver Transplantation, 24(2), 166-170. https://doi.org/10.1002/lt.25003
  5. Lefere, S., & Tacke, F. (2019). Macrophages in obesity and non-alcoholic fatty liver disease: Crosstalk with metabolism. JHEP Reports, 1(1), 30-43. https://doi.org/10.1016/j.jhepr.2019.02.004
  6. Friedman, S. L., Neuschwander-Tetri, B. A., Rinella, M., & Sanyal, A. J. (2018). Mechanisms of NAFLD development and therapeutic strategies. Nature Medicine, 24(7), 908–922. https://doi.org/10.1038/s41591-018-0104-9
  7. Konerman, M. A., Jones, J. C., & Harrison, S. A. (2018). Pharmacotherapy for Nash: Current and emerging. Journal of Hepatology, 68(2), 362-375. https://doi.org/10.1016/j.jhep.2017.10.015
  8. Dulai, P. S., Singh, S., Patel, J., Soni, M., Prokop, L. J., Younossi, Z., Sebastiani, G., Ekstedt, M., Hagstrom, H., Nasr, P., Stal, P., Wong, V. W.-S., Kechagias, S., Hultcrantz, R., & Loomba, R. (2017). Increased risk of mortality by fibrosis stage in nonalcoholic Fatty Liver Disease: Systematic review and meta-analysis. Hepatology, 65(5), 1557-1565. https://doi.org/10.1002/hep.29085
  9. Lee, Y. W., & Yarrington, C. D. (2017). Obstetric outcomes in women with nonalcoholic fatty liver disease. Metabolic Syndrome and Related Disorders, 15(8), 387-392. https://doi.org/10.1089/met.2017.0058
  10. Lao, T. T. (2020). Implications of abnormal liver function in pregnancy and non-alcoholic fatty liver disease. Best Practice & Research Clinical Obstetrics & Gynaecology, 68, 2-11. https://doi.org/10.1016/j.bpobgyn.2020.02.011
  11. Azzaroli, F., Mazzella, G., Marchesini, G., Brodosi, L., & Petroni, M. L. (2020). Fatty liver in pregnancy: A narrative review of two distinct conditions. Expert Review of Gastroenterology & Hepatology, 14(2), 127-135. https://doi.org/10.1080/17474124.2020.1715210
  12. Sarkar, M., Grab, J., Dodge, J. L., Gunderson, E. P., Rubin, J., Irani, R. A., Cedars, M., & Terrault, N. (2020). Non-alcoholic fatty liver disease in pregnancy is associated with adverse maternal and perinatal outcomes. Journal of Hepatology, 73(3), 516-522. https://doi.org/10.1016/j.jhep.2020.03.049
  13. Duan, Y., Pan, X., Luo, J., Xiao, X., Li, J., Bestman, P. L., & Luo, M. (2022). Association of inflammatory cytokines with non-alcoholic fatty liver disease. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.880298
  14. Westbrook, R. H., Dusheiko, G., & Williamson, C. (2016). Pregnancy and liver disease. Journal of Hepatology, 64(4), 933-945. https://doi.org/10.1016/j.jhep.2015.11.030
  15. Chen, J., Zhou, H., Jin, H., & Liu, K. (2022). Role of inflammatory factors in mediating the effect of lipids on nonalcoholic fatty liver disease: A two-step, multivariable Mendelian randomization study. Nutrients, 14(20), 4434. https://doi.org/10.3390/nu14204434
  16. Dufour, J. F., Oneta, C. M., Gonvers, J. J., Bihl, F., Cerny, A., Cereda, J. M., Zala, J. F., Helbling, B., Steuerwald, M., & Zimmermann, A. (2006). Randomized placebo-controlled trial of Ursodeoxycholic acid with vitamin E in nonalcoholic steatohepatitis. Clinical Gastroenterology and Hepatology, 4(12), 1537-1543. https://doi.org/10.1016/j.cgh.2006.09.025
  17. Haedrich, M., & Dufour, J.-F. (2011). UDCA for NASH: End of the story? Journal of Hepatology, 54(5), 856-858. https://doi.org/10.1016/j.jhep.2010.10.009
  18. Ratziu, V., Francque, S., & Sanyal, A. (2022). Breakthroughs in therapies for Nash and remaining challenges. Journal of Hepatology, 76(6), 1263-1278. https://doi.org/10.1016/j.jhep.2022.04.002
  19. Ratziu, V., de Ledinghen, V., Oberti, F., Mathurin, P., Wartelle-Bladou, C., Renou, C., Sogni, P., Maynard, M., Larrey, D., Serfaty, L., Bonnefont-Rousselot, D., Bastard, J.-P., Rivière, M., & Spénard, J. (2011). A randomized controlled trial of high-dose ursodesoxycholic acid for nonalcoholic steatohepatitis. Journal of Hepatology, 54(5), 1011-1019. https://doi.org/10.1016/j.jhep.2010.08.030
  20. Geier, A., Rinella, M. E., Balp, M.-M., McKenna, S. J., Brass, C. A., Przybysz, R., Cai, J., Knight, A., Gavaghan, M., Howe, T., Rosen, D., & Ratziu, V. (2021). Real-world burden of nonalcoholic steatohepatitis. Clinical Gastroenterology and Hepatology, 19(5), 1020-1029.e7. https://doi.org/10.1016/j.cgh.2020.06.064
  21. Oseini, A. M., & Sanyal, A. J. (2017). Therapies in non-alcoholic steatohepatitis (NASH). Liver International, 37, 97-103. https://doi.org/10.1111/liv.13302
  22. Pierantonelli, I., & Svegliati-Baroni, G. (2019). Nonalcoholic fatty liver disease: Basic pathogenetic mechanisms in the progression from NAFLD to nash. Transplantation, 103(1). https://doi.org/10.1097/tp.0000000000002480
  23. Sasso, M., Miette, V., Sandrin, L., & Beaugrand, M. (2012). The controlled attenuation parameter (CAP): A novel tool for the non-invasive evaluation of steatosis using Fibroscan®. Clinics and Research in Hepatology and Gastroenterology, 36(1), 13-20. https://doi.org/10.1016/j.clinre.2011.08.001
  24. Goldstein, R. F., Abell, S. K., Ranasinha, S., Misso, M., Boyle, J. A., Black, M. H., Li, N., Hu, G., Corrado, F., Rode, L., Kim, Y. J., Haugen, M., Song, W. O., Kim, M. H., Bogaerts, A., Devlieger, R., Chung, J. H., & Teede, H. J. (2017). Association of gestational weight gain with maternal and infant outcomes. JAMA, 317(21), 2207. https://doi.org/10.1001/jama.2017.3635
  25. Lim, A. W., Van Schalkwyk, M. C., Maani Hessari, N., & Petticrew, M. P. (2019). Pregnancy, fertility, breastfeeding, and alcohol consumption: An analysis of framing and completeness of information disseminated by alcohol industry–funded organizations. Journal of Studies on Alcohol and Drugs, 80(5), 524-533. https://doi.org/10.15288/jsad.2019.80.524
  26. Dyah, A., & Rahadina, R. (2021). Metabolic associated fatty liver disease and adverse maternal and fetal outcomes: A systematic review and meta-analysis. Clinical and Experimental Hepatology, 7(3), 305-311. https://doi.org/10.5114/ceh.2021.109228
  27. Qian, Y., Zhang, Y., Fan, X., Yan, H., Li, X., Fan, Y., Song, Y., Ma, S., Hu, Z., Gao, X., & Yang, J. (2022). Nonalcoholic fatty liver disease and adverse pregnancy outcomes in women with normal prepregnant weight. The Journal of Clinical Endocrinology & Metabolism, 108(2), 463-471. https://doi.org/10.1210/clinem/dgac567
  28. Li, N., & Zhao, H. (2021). Role of carnitine in non-alcoholic fatty liver disease and other related diseases: An update. Frontiers in Medicine, 8. https://doi.org/10.3389/fmed.2021.689042
  29. Dufour, J.-F., Anstee, Q. M., Bugianesi, E., Harrison, S., Loomba, R., Paradis, V., Tilg, H., Wong, V. W.-S., & Zelber-sagi, S. (2022). Current therapies and new developments in Nash. Gut, 71(10), 2123-2134. https://doi.org/10.1136/gutjnl-2021-326874

Downloads

Published

2023-03-28

How to Cite

1.
Bahnii LV, Heriak SM, Bahnii NI. The state of the cytokine profile in pregnant women with non-alcoholic fatty liver disease at the stage of non-alcoholic steatohepatitis with varying degrees of comorbid obesity under the influence of the developed complex therapy program. Zaporozhye Medical Journal [Internet]. 2023Mar.28 [cited 2026May16];25(2):136-41. Available from: https://zmj.zsmu.edu.ua/article/view/268274

Issue

Vol. 25 No. 2 (2023)

Section

Original research

License

Authors who publish with this journal agree to the following terms:

Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.  Лицензия Creative Commons