Dynamic Changes in Ex Vivo T-Cell Function After Viral Clearance in Chronic HCV Infection.

Abstract

BACKGROUND:

Direct-acting antiviral (DAA) agents can successfully treat chronic hepatitis C virus (HCV) infection. However, the ex vivo HCV-specific T-cell function following viral clearance remains unknown.

METHODS:

We investigated functional alterations and phenotypic changes in ex vivo HCV-specific CD8+ T cells with a longitudinal analysis of 41 patients with chronic HCV infection who were undergoing DAA treatment.

RESULTS:

A patient subset exhibited a significantly increased T-cell response (mainly CD8+ T cells) at week 4 of treatment. However, this increased T-cell response diminished in later weeks. Relative to pretreatment levels, the ex vivo HCV-specific CD8+ T-cell frequency decreased at 12 weeks after the end of treatment, along with a decreased antigen-experienced CD8+ T-cell population. DAA treatment increased the proliferative capacity of HCV-specific CD8+ T cells, but this change was not correlated with ex vivo function. Patients experiencing viral breakthrough or relapse exhibited defective restoration of T-cell function.

CONCLUSION:

Our present results indicated that DAA-mediated viral clearance only transiently restored ex vivo T-cell function, suggesting a need to enhance T-cell function in DAA-treated patients.

• Authors: Ji Won Han, Pil Soo Sung, Kyung Hwan Kim, Seon-Hui Hong, Eui-Cheol Shin, Myeong Jun Song, Su-Hyung Park
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 220 Issue 8 Pg. 1290-1301 (09 13 2019) ISSN: 1537-6613 [Electronic] United States
• PMID: 31152667 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

Chemical References

• Antiviral Agents

Topics

• Adult
• Aged
• Aged, 80 and over
• Antiviral Agents (pharmacology, therapeutic use)
• CD8-Positive T-Lymphocytes (drug effects, immunology)
• Cell Proliferation (drug effects)
• Female
• Hepacivirus (drug effects, immunology, isolation & purification)
• Hepatitis C, Chronic (drug therapy, immunology, virology)
• Humans
• Male
• Middle Aged
• Prospective Studies
• Recurrence
• Sustained Virologic Response
• Time Factors