Shu-Fen Wu1,2, Chih-Wei Tseng3,4, Yun-Che Ho1, Yen-Chun Chen3, Ping-Hung Ko3, Yi-Ting He3, Kuo-Chih Tseng5,6. 1. Department of Biomedical Sciences and Institute of Molecular Biology, National Chung Cheng University, Chia-yi, Taiwan. 2. Center for Innovative Research on Aging Society (CIRAS), National Chung Cheng University, Chia-yi, Taiwan. 3. Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No 2, Ming-Shen Road, Dalin Town, Chia-yi, 622, Taiwan. 4. School of Medicine, Tzuchi University, Hualien, Taiwan. 5. Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No 2, Ming-Shen Road, Dalin Town, Chia-yi, 622, Taiwan. tsengkuochih@gmail.com. 6. School of Medicine, Tzuchi University, Hualien, Taiwan. tsengkuochih@gmail.com.
Abstract
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.
BACKGROUNDS: Regulatory T cells (Tregs) affect the pathogenesis of chronic hepatitis C (CHC) infection. AIMS: This study evaluated the function of Tregs in CHCpatients receiving the standard direct-acting antiviral agents (DAA) treatment. METHODS:CHCpatients (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 CHCpatients receiving DAA therapy. The expression of IFN-γ, TNF-α, IL-10, and TGF-β parallelled Treg function.
Entities:
Keywords:
DAA; Function; Hepatitis C; Inhibition; Regulatory T cells
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