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. 2023 Jun 27;13(13):2187.
doi: 10.3390/diagnostics13132187.

Association of NK Cells with the Severity of Fibrosis in Patients with Chronic Hepatitis C

Anna Kleczka  1 , Bogdan Mazur  2 , Krzysztof Tomaszek  3 , Andrzej Gabriel  3 , Radosław Dzik  4 , Agata Kabała-Dzik  1
Affiliations

Association of NK Cells with the Severity of Fibrosis in Patients with Chronic Hepatitis C

Anna Kleczka et al. Diagnostics (Basel). .

Abstract

Some NK cell subpopulations may be involved in the modulation of fibrogenesis in the liver. The aim of the study was to evaluate the relationship between the number and phenotype of NK cell subsets in peripheral blood (PB) and total NK cell percentage, population density and the degree of liver fibrosis of patients infected with hepatitis C virus (HCV+). The study group consisted of 56 HCV+ patients, divided into two subgroups: patients with mild or moderate fibrosis and patients with advanced liver fibrosis or cirrhosis (F ≥ 3 in METAVIR classification). The preparations were stained with H-E and AZAN staining. NK cells were targeted with anti-CD56 antibody and identified automatically in situ using the DakoVision system. Assessment of different NK cell subsets in PB was performed with the flow cytometry technique. In the PB of HCV+ patients with advanced liver fibrosis, there was a lower proportion of CD62L+; CD62L+/CD94++; CD27+; CD127+/CD27+ and CXCR3+/CD27+ NK subsets, as compared to patients with mild/moderate liver fibrosis. The results also showed no association between total PB NK cell level and total intrahepatic NK cell population density between patients with mild/moderate fibrosis and with advanced liver fibrosis. However, positive correlations between the PB levels of CD94+ and CD62L+ NK cell subsets and the intrahepatic total NK cell percentage and population density in the liver, irrespectively to the extent of fibrosis, were observed. Additionally, positive correlation was found between the PB CXCR3+/CD94+ NK cell percentages and intrahepatic NK cell percentages in patients with advanced hepatic fibrosis. Lower blood availability of specific NK subsets in patients with chronic type C hepatitis might be a cause of progression of liver fibrosis via insufficient control over hepatic stellate cells.

Keywords: NK cells; chronic hepatitis C; fibrosis; flow cytometry; hepatic stellate cells.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flowchart explaining patient inclusion/exclusion criteria.
Figure 2
Figure 2
Results of the study of the percentage of different NK cell subpopulations in the groups of patients with none/mild/moderate liver fibrosis (F0/F1/F2) and with advanced hepatic fibrosis or cirrhosis (F3/F4). The graphs show: (a) percentage of CD16+ natural killer cells in whole blood from groups (antibody mix 1); (b) percentage of CD16+ natural killer cells in whole blood from groups (antibody mix 2); (c) mean percentage of CD62L+ natural killer cells in whole blood in the analyzed groups; (d) mean percentage of CD62L+ CD94++ natural killer cells in whole blood in the analyzed groups; (e) mean percentage of CD27+ natural killer cells in whole blood in the analyzed groups. (f) mean percentage of CD27+ CD127+ natural killer cells in whole blood in the analyzed groups; (g) mean percentage of CXCR3+ CD27+ natural killer cells in whole blood in the analyzed groups. * Statistically significant difference in the percentage of the NK cell population between analyzed groups; p < 0.05.
Figure 3
Figure 3
Sample results of the cytometric analysis with specified NK cell phenotypes.
Figure 4
Figure 4
Liver biopsy with marked AOI. In the frames, you can see the measurement values of the area of the selection. Magnification approx. 120×.
Figure 5
Figure 5
(A) Portal space with marked AOI (blue line). Magnification approx. 500×. (B) AOI from the previous figure with the output of the HistoQuant module. CD56 cells marked in green. Magnification approx. 430×. (C) The same AOI with the output of the NuclearQuant module. Blue indicates portal space lymphocytes, yellow and red CD56 lymphocytes. Magnification approx. 430×. (D) AOI from the previous figure with the result of both counting modules superimposed. Blue contour—lymphocytes; red, yellow and green contours—CD56 cells. Visible complementation of the work of the counting modules. Magnification approx. 480×.
Figure 6
Figure 6
Correlation of the percentage of CD62L+ natural killer cells and the population density of CD56 lymphocytes.
Figure 7
Figure 7
Correlation of the percentage of CD94+ natural killer cells in whole blood and the percentage of CD56 lymphocytes in the liver.
Figure 8
Figure 8
Correlation of the percentage of CXCR3+ CD94+ natural killer cells in peripheral whole blood and the population density of CD56 lymphocytes.
Figure 9
Figure 9
Correlation of the number of CXCR3+ CD94+ natural killer cells in peripheral whole blood and the percentage of intrahepatic CD56+ lymphocytes in the group of patients with advanced liver fibrosis (≥F3).
Figure 10
Figure 10
Correlation between the percentage of CXCR3+ CD94+ NK cells in whole peripheral blood and the population density index of intrahepatic CD56+ lymphocytes in the group of patients with advanced liver fibrosis (≥F3).
Figure 11
Figure 11
Correlation between the percentage of CD94+ NK cells in peripheral whole blood and the population index of intrahepatic lymphocytes in the patients with none/mild/moderate fibrosis.
Figure 12
Figure 12
Correlation between the number of CD94++ NK cells in whole peripheral blood and the population density of lymphocytes in the liver.
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