Treg cells in the course of chronic hepatitis C virus infection partially normalize in longitudinal observation after successful DAA treatment regardless of hepatic fibrosis stage

Agata Zientarska; Mariusz Kaczmarek; Iwona Mozer-Lisewska; Arleta Kowala-Piaskowska; Aleksandra Witkowska; Jan Żeromski

doi:10.5114/ceh.2021.107122

Treg cells in the course of chronic hepatitis C virus infection partially normalize in longitudinal observation after successful DAA treatment regardless of hepatic fibrosis stage

Clin Exp Hepatol. 2021 Jun;7(2):196-204. doi: 10.5114/ceh.2021.107122. Epub 2021 Jun 30.

Authors

Agata Zientarska¹, Mariusz Kaczmarek^{2

3}, Iwona Mozer-Lisewska¹, Arleta Kowala-Piaskowska¹, Aleksandra Witkowska¹, Jan Żeromski⁴

Affiliations

¹ Chair and Department of Infectious Diseases, Hepatology and Acquired Immunodeficiencies, Karol Marcinkowski University of Medical Sciences, Poznan, Poland.
² Chair of Clinical Immunology and Department of Cancer Immunology, Karol Marcinkowski University of Medical Sciences, Poznan, Poland.
³ Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, Poznan, Poland.
⁴ Chair of Clinical Immunology, Karol Marcinkowski University of Medical Sciences, Poznan, Poland.

Abstract

Aim of the study: Elevated circulating CD4+ CD25+ Foxp3+ regulatory T cells in patients with chronic hepatitis C (CHC) play an unspecified role in liver fibrosis development. This study aimed to determine whether Treg cells diminish after successful treatment with directacting antivirals (DAA) in patients at different liver fibrosis stages.

Material and methods: We examined 44 patients with CHC (including 29 with liver cirrhosis) seven days before DAA treatment (T0), six months later (T1) and then 22 of them were examined one year (T2) after the first dose. Subsequently, these were compared with 28 volunteers without hepatitis C virus (HCV) (15 with excessive alcohol intake). We assessed the degree of liver fibrosis with FibroScan, aspartate transaminase (AST) to platelet ratio index (APRI), FibroIndex, the Forns index and Fib-4. Circulating Treg cells were measured using flow cytometry.

Results: All patients achieved a sustained virological response (SVR). After the treatment, all liver fibrosis indicators decreased significantly. The number of circulating Tregs was lower in healthy controls than in patients with CHC (0.0066 × 10³ cells/µl and 0.0084 × 10³ cells/µl, respectively, p = 0.048). After the treatment we observed an insignificant change to 0.0047 × 10³ cells/µl for T1 (p > 0.05) and a significant fall to 0.0041 × 10³ cells/µl for T2 (p = 0.03). There was no correlation between the degree of hepatic fibrosis and number of Tregs or post-treatment dynamics.

Conclusions: Our study shows that Treg cells normalize gradually over a prolonged period of time after a successful DAA treatment. Their number and dynamics remain independent of liver fibrosis degree. The correlation of this revelation with metabolic disorders, increased susceptibility to infections or persistent risk of HCC remains unclear.

Keywords: Treg cells; hepatitis C; liver fibrosis.