IL-23/IL-17 Axis in Chronic Hepatitis C and Non-Alcoholic Steatohepatitis-New Insight into Immunohepatotoxicity of Different Chronic Liver Diseases

Ankica Vujovic; Andjelka M Isakovic; Sonja Misirlic-Dencic; Jovan Juloski; Milan Mirkovic; Andja Cirkovic; Marina Djelic; Ivana Milošević

doi:10.3390/ijms241512483

IL-23/IL-17 Axis in Chronic Hepatitis C and Non-Alcoholic Steatohepatitis-New Insight into Immunohepatotoxicity of Different Chronic Liver Diseases

Int J Mol Sci. 2023 Aug 5;24(15):12483. doi: 10.3390/ijms241512483.

Authors

Ankica Vujovic^{1

2}, Andjelka M Isakovic^{3

4}, Sonja Misirlic-Dencic^{3

4}, Jovan Juloski^{2

5}, Milan Mirkovic⁶, Andja Cirkovic⁷, Marina Djelic⁸, Ivana Milošević^{1

2}

Affiliations

¹ Clinic for Infectious and Tropical Diseases, University Clinical Center of Serbia, 11 000 Belgrade, Serbia.
² Faculty of Medicine, University of Belgrade, 11 000 Belgrade, Serbia.
³ Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, 11 000 Belgrade, Serbia.
⁴ Center of Excellence for Redox Medicine, 11 000 Belgrade, Serbia.
⁵ Zvezdara Medical University Center, Surgery Clinic "Nikola Spasic", 11 000 Belgrade, Serbia.
⁶ Institute for Orthopedic Surgery "Banjica", 11 000 Belgrade, Serbia.
⁷ Department of Medical Statistics, Faculty of Medicine, University of Belgrade, 11 000 Belgrade, Serbia.
⁸ Institute of Medical Physiology, Faculty of Medicine, University of Belgrade, 11 000 Belgrade, Serbia.

Abstract

Considering the relevance of the research of pathogenesis of different liver diseases, we investigated the possible activity of the IL-23/IL-17 axis on the immunohepatotoxicity of two etiologically different chronic liver diseases. A total of 36 chronic hepatitis C (CHC) patients, 16 with (CHC-SF) and 20 without significant fibrosis (CHC-NSF), 19 patients with non-alcoholic steatohepatitis (NASH), and 20 healthy controls (CG) were recruited. Anthropometric, biochemical, and immunological cytokines (IL-6, IL-10, IL-17 and IL-23) tests were performed in accordance with standard procedure. Our analysis revealed that a higher concentration of plasma IL-23 was associated with NASH (p = 0.005), and a higher concentration of plasma IL-17A but a lower concentration of plasma IL-10 was associated with CHC in comparison with CG. A lower concentration of plasma IL-10 was specific for CHC-NSF, while a higher concentration of plasma IL-17A was specific for CHC-SF in comparison with CG. CHC-NSF and CHC-SF groups were distinguished from NASH according to a lower concentration of plasma IL-17A. Liver tissue levels of IL-17A and IL-23 in CHC-NSF were significantly lower in comparison with NASH, regardless of the same stage of the liver fibrosis, whereas only IL-17A tissue levels showed a difference between the CHC-NSF and CHC-SF groups, namely, a lower concentration in CHC-NSF in comparison with CHC-SF. In CHC-SF and NASH liver tissue, IL17-A and IL-23 were significantly higher in comparison with plasma. Diagnostic accuracy analysis showed significance only in the concentration of plasma cytokines. Plasma IL-6, IL-17A and IL-23 could be possible markers that could differentiate CHC patients from controls. Plasma IL-23 could be considered a possible biomarker of CHC-NSF patients in comparison with controls, while plasma IL-6 and IL-17-A could be biomarkers of CHC-SF patients in comparison with controls. The most sophisticated difference was between the CHC-SF and CHC-NSF groups in the plasma levels of IL-10, which could make this cytokine a useful biomarker of liver fibrosis.

Keywords: IL-23/IL-17 axis; chronic hepatitis C; immunohepatotoxicity; non-alcoholic steatohepatitis.

Grants and funding

This study received funding from the Ministry of Education, Science and Technological Development, Republic of Serbia (grant agreement no. 451-03-9/2021-14/200110).