Русский
Prognostic value of serum biomarkers in case of chronic hepatitis C
DOI: https://dx.doi.org/10.18565/therapy.2024.7.28-34
Tereshkin N.A., Makashova V.V., Ponezheva Zh.B., Omarova Kh.G., Muzyka A.D., Gorelov A.V.
1) Central Research Institute of Epidemiology of Rospotrebnadzor, Moscow; 2) I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University); 3) Russian University of Medicine of the Ministry of Healthcare of Russia, Moscow
The aim: to assess the prognostic value of biomarkers in the development of LC as a result of CHC.
Material and methods. 107 patients, including 66 with CHC and 41 with LC as a result of CHC were involved in the study. Osteopontin (OPN) and hepatocyte growth factor (HGF) were determined in the blood serum by enzyme immunoassay methodic. The stage of liver fibrosis (F) was detected using fibroelastometry on FibroScan medicine. To assess the diagnostic significance of fibrosis biomarkers in predicting the development of LC, the ROC curves analysis method was used.
Results. In patients with F0–F1, median of OPN concentration was 12.5 ng/ml, while in patients with F3–F4 it was 31.25 ng/ml (p = 0.004). In patients with F0–F1, median of HGF level was 441 pg/ml, while in patients with F3–F4 it was 1200 pg/ml (p < 0.001). Correlation of liver tissue stiffness indexes with OPN concentration showed a direct relationship of noticeable tightness, while with the HGF level it showed a direct relationship of high tightness (ρ = 0.716; p = 0.009). Threshold level of OPN in the cut-off point was 23 ng/ml, while for HGF it was 935 pg/ml. Sensitivity and specificity of OPN model were 88.2 and 82.8%, HGF – 75 and 88%, respectively.
Conclusion. With the development of liver cirrhosis, there is an increase in both OPN and HGF concentration. The level of OPN significantly correlates with the stage of fibrosis. A direct relationship of high tightness was fixed between the level of HGF and stiffness of the liver tissue. Sensitivity and specificity of biomarkers were estimated as excellent, since the areas under the curves were more than 0.8. Obtained results indicate the possibility of using OPN and HGF as biomarkers of progressive liver fibrosis and cirrhosis in the outcome of chronic hepatitis C.
Literature
1. Bojanic K., Bogojevic M.S., Vukadin S. et al. Noninvasive fibrosis assessment in chronic hepatitis C infection: An update. J Clin Trans Hepatol. 2023; 11(5): 1228–38. https://doi.org/10.14218/JCTH.2022.00365. PMID: 37577224. PMCID: PMC10412701. 2. World Health Organization. Hepatitis C. URL: https://www.who.int/news-room/fact-sheets/detail/hepatitis-c (date of access – 28.08.2024). 3. Hsu C.C., Gopalakrishna H., Mironova M. et al. Risk of hepatocellular carcinoma after spontaneous clearance of hepatitis C virus and in noncirrhosis chronic hepatitis C patients with sustained virological response: A systematic review. Clin Infect Dis. 2023; 77(Suppl 3): S245–S256. https://doi.org/10.1093/cid/ciad380. PMID: 37579210. PMCID: PMC10425144. 4. World Health Organization. Global health sector strategy on viral hepatitis 2016–2021. URL: http://apps.who.int/iris/bitstream/10665/246177/1/WHO-HIV-2016.06-eng.pdf (date of access – 28.08.2024). 5. Antoniou T., Pritlove C., Shearer D. et al. Accessing hepatitis C direct acting antivirals among people living with hepatitis C: A qualitative study. Int J Equity Health. 2023; 22(1): 112. https://doi.org/10.1186/s12939-023-01924-4. PMID: 37280588. PMCID: PMC10243011. 6. World Health Organization. Global Progress Report on HIV, Viral Hepatitis and Sexually Transmitted Infections, 2021. URL: https://www.who.int/publications/i/item/9789240027077 (date of access – 28.08.2024). 7. Suan M.A.M., Chan H.K., Sem X. et al. Diagnostic performance of two non-invasive biomarkers used individually and in sequential combination for cirrhosis associated with hepatitis C virus infection. Sci Rep. 2022; 12(1): 20153. https://doi.org/10.1038/s41598-022-24612-9. PMID: 36418369. PMCID: PMC9684447. 8. Zhang C.Y., Liu S., Yang M. Treatment of liver fibrosis: Past, current, and future. World J Hepatol. 2023; 15(6): 755–74. https://doi.org/10.4254/wjh.v15.i6.755. PMID: 37397931. PMCID: PMC10308286. 9. Gharbia S., Nazarie S.R., Dinescu S. et al. Adipose-derived stem cells (ADSCs) supplemented with hepatocyte growth factor (HGF) attenuate hepatic stellate cell activation and liver fibrosis by inhibiting the TGF-β/Smad signaling pathway in chemical-induced liver fibrosis associated with diabetes. Cells. 2022; 11(21): 3338. https://doi.org/10.3390/cells11213338. PMID: 36359733. PMCID: PMC9653841. 10. Geng A., Flint E., Bernsmeier C. Plasticity of monocytes and macrophages in cirrhosis of the liver. Front Netw Physiol. 2022; 2: 937739. https://doi.org/10.3389/fnetp.2022.937739. PMID: 36926073. PMCID: PMC10013015. 11. Song Z., Chen W., Athavale D. et al. Osteopontin takes center stage in chronic liver disease. Hepatology. 2021; 73(4): 1594–608. https://doi.org/10.1002/hep.31582. PMID: 32986864. PMCID: PMC8106357. 12. Bruha R., Vitek L., Smid V. Osteopontin – A potential biomarker of advanced liver disease. Ann Hepatol. 2020; 19(4): 344–52. https://doi.org/10.1016/j.aohep.2020.01.001. PMID: 32005637. 13. Marquez-Coello M., Arizcorreta A., Rodríguez-Pardo M. et al. Modifications of liver stiffness and CXCL4, TGF-β1 and HGF are similar in HCV- and HIV/HCV-infected patients after DAAs. Sci Rep. 2021; 11(1): 9824. https://doi.org/10.1038/s41598-021-89370-6. PMID: 33972651. PMCID: PMC8110591. 14. Huang W., Zhu G., Huang M. et al. Plasma osteopontin concentration correlates with the severity of hepatic fibrosis and inflammation in HCV-infected subjects. Clin Chim Acta. 2010; 411(9–10): 675–78. https://doi.org/10.1016/j.cca.2010.01.029. PMID: 20138033. 15. Matsue Y., Tsutsumi M., Hayashi N. et al. Serum osteopontin predicts degree of hepatic fibrosis and serves as a biomarker in patients with hepatitis C virus infection. PLoS One. 2015; 10(3): e0118744. https://doi.org/10.1371/journal.pone.0118744. PMID: 25760884. PMCID: PMC4356538.
About the Autors
Nikita A. Tereshkin, MD, postgraduate student of Central Research Institute of Epidemiology of Rospotrebnadzor. Address: 111123, Moscow, 3A Novogireevskaya St.
E-mail: nteryoshkin@gmail.com
ORСID: https://orcid.org/0009-0002-3541-4150
Vera V. Makashova, MD, Dr. Sci. (Medicine), professor, leading researcher at the Clinical Department of infectious pathology, Central Research Institute of Epidemiology of Rospotrebnadzor. Address: 111123, Moscow, 3A Novogireevskaya St.
E-mail: veramakashova@yandex.ru
ORСID: https://orcid.org/0000-0002-0982-3527
Zhanna B. Ponezheva, MD, Dr. Sci. (Medicine), head of the Clinical Department of infectious pathology, Central Research Institute of Epidemiology of Rospotrebnadzor. Address: 111123, Moscow, 3A Novogireevskaya St.
E-mail: doktorim@mail.ru
ORСID: http://orcid.org/0000-0002-6539-4878
Khadizhat G. Omarova, MD, PhD (Medicine), head of the Department of clinical research, Central Research Institute of Epidemiology of Rospotrebnadzor. Address: 111123, Moscow, 3A Novogireevskaya St.
E-mail: omarova71@inbox.ru
ORСID: http://orcid.org/0000-0002-9682-2230
Anna D. Muzyka, MD, PhD (Medicine), senior researcher at the Clinical Department of infectious pathology, Central Research Institute of Epidemiology of Rospotrebnadzor. Address: 111123, Moscow, 3A Novogireevskaya St.
E-mail: Amyzika@cmd.su
ORСID: https://orcid.org/0000-0002-2269-2533
Alexander V. Gorelov, MD, academician of RAS, Dr. Sci. (Medicine), professor, deputy director for science of Central Research Institute of Epidemiology of Rospotrebnadzor, professor of the Department of childhood diseases of I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University), head of the Department of infectious diseases and epidemiology of Russian University of Medicine of the Ministry of Healthcare of Russia. Address: 111123, Moscow, 3A Novogireevskaya St.
E-mail: zdn@cmd.su
ORCID: http://orcid.org/0000-0001-9257-0171
Similar Articles
