Diagnostic values of MMP-9 and TGF-1β in assessing the severity of liver fibrosis and the rate of its progression in patients with chronic hepatitis C GT 1 infection
DOI:
https://doi.org/10.14739/2310-1210.2023.4.276462Keywords:
chronic hepatitis C, viral infection, liver fibrosis, risk factors, cytokines, diagnosis, prognosisAbstract
Aim. The purpose of our work is to find out diagnostic values of serum MMP-9 and TGF-1β determination for assessing the severity of liver fibrosis and the rate of its progression in patients with chronic hepatitis C genotype 1 (CHC GT1) infection.
Materials and methods. 92 patients with CHC GT1 were examined. The severity of liver fibrosis was assessed by elastometry. The rate of liver fibrosis progression was calculated using the T. Poynard formula. Serum levels of TGF-1β and MMP-9 were measured by ELISA method.
Results. In patients with CHC GT1, the most noticeable changes in the serum parameters of fibrogenesis / fibrinolysis were observed in the presence of F 3–4. The probability of liver fibrosis stages F 3–4 was high at the serum levels of TGF-1β >12.03 pg/ml (p < 0.001), MMP-9 ≤987.20 pg/ml (p = 0.016), TGF-1β/MMP-9 ratio >0.011 (p < 0.001).
Fast liver fibrosis progression was more often registered in F 3–4 than in F 0–2 (62.9 % vs. 16.7 %, p < 0.0001). Increasing rate of liver fibrosis progression in these patients was confirmed by a higher ratio of TGF-1β/MMP-9 compared to that in patients with a slow rate of liver fibrosis progression (p < 0.05). The probability of fast liver fibrosis progression was high at the serum levels of TGF-1β >8.69 pg/ml (p < 0.001), MMP-9 ≤920.65 (p = 0.005), TGF-1β/MMP-9 ratio > 0.011 (p < 0.001).
Conclusions. The diagnostic value of MMP-9 and TGF-1β in assessing the liver fibrosis severity and the rate of its progression in patients with CHC GT1 has been defined. Cut-off levels of MMP-9, TGF-1β and the TGF-1β/MMP-9 ratio for stratification of patients with severe liver fibrosis and the fast rate of its progression have been proposed.
References
World Health Organization. (2022, June 24). Hepatitis C. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c
Khatun, M., & Ray, R. B. (2019). Mechanisms Underlying Hepatitis C Virus-Associated Hepatic Fibrosis. Cells, 8(10), 1249. https://doi.org/10.3390/cells8101249
World Health Organization. (2021). Global progress report on HIV, viral hepatitis and sexually transmitted infections. Accountability for the global health sector strategies 2016-2021: actions for impact. Web Annex 1. Key data at a glance. http://apps.who.int/iris/bitstream/handle/10665/342808/9789240030985-eng.pdf
State Enterprise Center of Public Health of the Ministry of Health of Ukraine. (2022). Naiavnist kursiv dlia likuvannia virusnoho hepatytu S u rozrizi oblastei stanom na 1 travnia 2022 roku [Availability of courses for the treatment of viral hepatitis C by region as of May 1, 2022]. [in Ukrainian]. https://phc.org.ua/news/nayavnist-kursiv-dlya-likuvannya-virusnogo-gepatitu-s-u-rozrizi-oblastey-stanom-na-1-travnya
Agbim, U., & Asrani, S. K. (2019). Non-invasive assessment of liver fibrosis and prognosis: an update on serum and elastography markers. Expert review of gastroenterology & hepatology, 13(4), 361-374. https://doi.org/10.1080/17474124.2019.1579641
European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu, Clinical Practice Guideline Panel, Chair:, EASL Governing Board representative:, & Panel members: (2021). EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis - 2021 update. Journal of hepatology, 75(3), 659–689. https://doi.org/10.1016/j.jhep.2021.05.025
Kaur, N., Goyal, G., Garg, R., Tapasvi, C., Chawla, S., & Kaur, R. (2021). Potential role of noninvasive biomarkers during liver fibrosis. World journal of hepatology, 13(12), 1919-1935. https://doi.org/10.4254/wjh.v13.i12.1919
Binet, Q., Loumaye, A., Preumont, V., Thissen, J. P., Hermans, M. P., & Lanthier, N. (2022). Non-invasive screening, staging and management of metabolic dysfunction-associated fatty liver disease (MAFLD) in type 2 diabetes mellitus patients: what do we know so far ?. Acta gastro-enterologica Belgica, 85(2), 346-357. https://doi.org/10.51821/85.2.9775
Mateiko, H. B., & Prokofiev M. V. (2017.) Diahnostyka fibrozu pechinky u ditei, khvorykh na hepatyt C [Diagnosis of liver fibrosis in children with hepatitis C]. Dytiachyi likar, (3), 18-22. [in Ukrainian].
Poynard, T., Bedossa, P., & Opolon, P. (1997). Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet, 349(9055), 825-832. https://doi.org/10.1016/s0140-6736(96)07642-8
Besheer, T., El-Bendary, M., Elalfy, H., Abd El-Maksoud, M., Salah, M., Zalata, K., Elkashef, W., Elshahawy, H., Raafat, D., Elemshaty, W., Almashad, N., Zaghloul, H., El-Gilany, A. H., Abdel Razek, A. A., & Abd Elwahab, M. (2017). Prediction of Fibrosis Progression Rate in Patients with Chronic Hepatitis C Genotype 4: Role of Cirrhosis Risk Score and Host Factors. Journal of interferon & cytokine research, 37(3), 97-102. https://doi.org/10.1089/jir.2016.0111
Farci, P., Wollenberg, K., Diaz, G., Engle, R. E., Lai, M. E., Klenerman, P., Purcell, R. H., Pybus, O. G., & Alter, H. J. (2012). Profibrogenic chemokines and viral evolution predict rapid progression of hepatitis C to cirrhosis. Proceedings of the National Academy of Sciences of the United States of America, 109(36), 14562-14567. https://doi.org/10.1073/pnas.1210592109
Roehlen, N., Crouchet, E., & Baumert, T. F. (2020). Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives. Cells, 9(4), 875. https://doi.org/10.3390/cells9040875
Higashi, T., Friedman, S. L., & Hoshida, Y. (2017). Hepatic stellate cells as key target in liver fibrosis. Advanced drug delivery reviews, 121, 27-42. https://doi.org/10.1016/j.addr.2017.05.007
Rudnik, M., Hukara, A., Kocherova, I., Jordan, S., Schniering, J., Milleret, V., Ehrbar, M., Klingel, K., Feghali-Bostwick, C., Distler, O., Błyszczuk, P., & Kania, G. (2021). Elevated Fibronectin Levels in Profibrotic CD14+ Monocytes and CD14+ Macrophages in Systemic Sclerosis. Frontiers in immunology, 12, 642891. https://doi.org/10.3389/fimmu.2021.642891
Dewidar, B., Meyer, C., Dooley, S., & Meindl-Beinker, A. N. (2019). TGF-β in Hepatic Stellate Cell Activation and Liver Fibrogenesis-Updated 2019. Cells, 8(11), 1419. https://doi.org/10.3390/cells8111419
Abu El Makarem, M. A., El-Sagheer, G. M., & Abu El-Ella, M. A. (2018). The Role of Signal Transducer and Activator of Transcription 5 and Transforming Growth Factor-β1 in Hepatic Fibrosis Induced by Chronic Hepatitis C Virus Infection in Egyptian Patients. Medical principles and practice, 27(2), 115-121. https://doi.org/10.1159/000487308
Gorka-Dynysiewicz, J., Pazgan-Simon, M., & Zuwala-Jagiello, J. (2019). Pentraxin 3 Detects Clinically Significant Fibrosis in Patients with Chronic Viral Hepatitis C. BioMed research international, 2019, 2639248. https://doi.org/10.1155/2019/2639248
Elbanan, W. K., Fathy, S. A., Ibrahim, R. A., & Hegazy, M. G. A. (2020). Assessment of interleukin 17 and transforming growth factor-beta 1 in hepatitis C patients with disease progression. Tropical biomedicine, 37(4), 1093-1104. https://doi.org/10.47665/tb.37.4.1093
Didenko V. I., Klenina, I. A., Tatarchuk, O. M., Konenko, I. S., & Petishko, O. P. (2020). Diahnostychni markery prohresuvannia fibroznykh zmin pechinky u khvorykh na khronichni dyfuzni zakhvoriuvannia alkoholnoho genezu [Diagnostic markers of progression of fibrous liver changes in patients with chronic diffuse liver diseases of alcoholic genesis]. Visnyk medychnykh i biolohichnykh doslidzhen, 3(5), 47-52. [in Ukrainian]. https://doi.org/10.11603/bmbr.2706-6290.2020.3.11295
Khelemendyk, A. B., Riabokon, O. V., Riabokon, Yu. Yu., & Kalashnyk, K. V. (2021). Relationships between HBeAg status of patients with chronic hepatitis B and changes in serum TNF-α, viral load and severity of morphological changes in the liver according to non-invasive tests. Patologia, 18(1), 80-85. https://doi.org/10.14739/2310-1237.2021.1.228933
Cui, N., Hu, M., & Khalil, R. A. (2017). Biochemical and Biological Attributes of Matrix Metalloproteinases. Progress in molecular biology and translational science, 147, 1-73. https://doi.org/10.1016/bs.pmbts.2017.02.005
Fischer, T., & Riedl, R. (2019). Inhibitory Antibodies Designed for Matrix Metalloproteinase Modulation. Molecules, 24(12), 2265. https://doi.org/10.3390/molecules24122265
Badra, G., Lotfy, M., El-Refaie, A., Obada, M., Abdelmonem, E., Kandeel, S., & Fathy, A. (2010). Significance of serum matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in chronic hepatitis C patients. Acta microbiologica et immunologica Hungarica, 57(1), 29-42. https://doi.org/10.1556/AMicr.57.2010.1.3
Martinez-Castillo, M., Hernandez-Barragan, A., Flores-Vasconcelos, I., Galicia-Moreno, M., Rosique-Oramas, D., Perez-Hernandez, J. L., Higuera-De la Tijera, F., Montalvo-Jave, E. E., Torre-Delgadillo, A., Cordero-Perez, P., Muñoz-Espinosa, L., Kershenobich, D., & Gutierrez-Reyes, G. (2021). Production and activity of matrix metalloproteinases during liver fibrosis progression of chronic hepatitis C patients. World journal of hepatology, 13(2), 218-232. https://doi.org/10.4254/wjh.v13.i2.218
Tsomidis, I., Notas, G., Xidakis, C., Voumvouraki, A., Samonakis, D. N., Koulentaki, M., & Kouroumalis, E. (2022). Enzymes of Fibrosis in Chronic Liver Disease. Biomedicines, 10(12), 3179. https://doi.org/10.3390/biomedicines10123179
Roeb E. (2018). Matrix metalloproteinases and liver fibrosis (translational aspects). Matrix biology, 68-69, 463-473. https://doi.org/10.1016/j.matbio.2017.12.012
Zeremski, M., Dimova, R. B., Pillardy, J., de Jong, Y. P., Jacobson, I. M., & Talal, A. H. (2016). Fibrosis Progression in Patients With Chronic Hepatitis C Virus Infection. The Journal of infectious diseases, 214(8), 1164-1170. https://doi.org/10.1093/infdis/jiw332
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