Regulatory T Cell Function Modulated After Successful Direct-Acting Antiviral Treatment for Chronic Hepatitis C Patients

• Published in: Digestive diseases and sciences Vol. 65; no. 5; pp. 1385 - 1395
• Main Authors: Wu, Shu-Fen, Tseng, Chih-Wei, Ho, Yun-Che, Chen, Yen-Chun, Ko, Ping-Hung, He, Yi-Ting, Tseng, Kuo-Chih
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-05-2020; Springer; Springer Nature B.V
• Subjects: Aged; Antiviral Agents - therapeutic use; Antiviral drugs; Biochemistry; Biological response modifiers; Cytokines; Cytokines - blood; Drug therapy; Female; Gastroenterology; Genotype; Health aspects; Hepacivirus - genetics; Hepatitis; Hepatitis C; Hepatitis C virus; Hepatitis C, Chronic - blood; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - virology; Hepatology; Humans; Interferon; Male; Medicine; Medicine & Public Health; Middle Aged; Oncology; Original Article; RNA, Viral - blood; Sustained Virologic Response; T cells; T-Lymphocytes, Regulatory - virology; Transforming growth factors; Transplant Surgery; Tumor necrosis factor; Tumor necrosis factor-TNF; Function; Inhibition; Hepatitis C; Regulatory T cells; DAA
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-019-05850-w

Backgrounds
Regulatory T cells (Tregs) affect the pathogenesis of chronic hepatitis C (CHC) infection.
Aims
This study evaluated the function of Tregs in CHC patients receiving the standard direct-acting antiviral agents (DAA) treatment.
Methods
CHC patients (
n
 = 20) who received DAA treatment, clinical data, and function of Tregs were checked at baseline, Week 4, end of treatment (EOT), and 12 weeks after EOT (SVR 12). Treg-mediated inhibition was measured. The cytokine expression and fold change of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-10, and transforming growth factor (TGF)-β with/without Treg inhibition were also detected.
Results
The cohort included 14 females with a mean age of 59.8 ± 11.5 years. Nineteen had HCV genotype 1. The HCV RNA level was 6.17 ± 0.70 log IU/mL. All patients reached the sustained virologic response. The frequency of CD4
+
Foxp3
+
T cells decreased from baseline to EOT and returned at SVR 12. The inhibitory function of Tregs decreased during treatment and then restored (baseline vs. EOT,
P
 = 0.0393; EOT vs. SVR 12,
P
 = 0.0052). The cytokine expression and fold change of IFN-γ and TNF-α were highest at EOT and then decreased at SVR 12. The fold change of IL-10 was lowest at EOT and then increased at SVR 12. The fold change of TGF-β was significantly increased at Week 4 and SVR 12 compared to baseline.
Conclusions
The frequency and inhibitory function of Tregs declined gradually from baseline to EOT and then increased from EOT to SVR 12 in CHC patients receiving DAA therapy. The expression of IFN-γ, TNF-α, IL-10, and TGF-β parallelled Treg function.