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ISSN: 2392-1099
Clinical and Experimental Hepatology
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2/2021
vol. 7
 
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abstract:
Original paper

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
1
,
Mariusz Kaczmarek
2, 3
,
Iwona Mozer-Lisewska
1
,
Arleta Kowala-Piaskowska
1
,
Aleksandra Witkowska
1
,
Jan Żeromski
4

  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
Clin Exp HEPATOL 2021; 7, 2: 196-204
DOI: https://doi.org/10.5114/ceh.2021.107122
Online publish date: 2021/07/13
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Introduction
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:

hepatitis C, liver fibrosis, Treg cells
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