Combination Therapies Reduce Treg Functions in CHC Patients

by Caleb Sooknanan ’20

Figure 1: Shown here is an example of Scopulariopsis, a genus of fungi capable of living in the absence of soil, air, plant debris, and dung. A new species of this fungi was recently discovered in cotton plants in Hangzhou, China.

Figure 1: Shown here is an example of Scopulariopsis, a genus of fungi capable of living in the absence of soil, air, plant debris, and dung. A new species of this fungi was recently discovered in cotton plants in Hangzhou, China.

Regulatory T-Cells, or Tregs, are important contributors to the development of chronic hepatitis C (CHC) infections in patients. Oral antiviral agents are the most common treatments for CHC infections in most Western countries, while pegylated interferon (PEG-IFN) treatment is the standard therapy in many Asian countries. PEG-IFNs are interferons that attach to polyethylene glycol molecules to trigger sustained virological responses (SVR) in hepatitis C patients. PEG-IFN treatments are sometimes performed with ribavirin (RBV), an antiviral drug normally used to treat lung infections that when administered orally can treat hepatitis C. However, studies have been inconsistent in determining how Tregs are affected in CHC patients receiving combination therapy. When antiviral treatments were used, CHC patients with inflammation had the same Treg frequency as that of CHC patients with normal liver function, but Tregs more commonly suppressed effector T-cell proliferation in patients with inflammation. Still, more research is needed to understand Treg function in CHC patients receiving combination therapy. Dr. Kuo-Chih Tseng and his team at Tzuchi University in Taiwan conducted a study to analyze the frequency and function patterns of Tregs in CHC patients receiving combination therapy.

The study sample comprised 30 CHC patients who were treated with PEG-IFN and RBV between November 2008 and August 2010 at the Dalin Tzu Chi General Hospital in southern Taiwan. The patients showed evidence of anti-hepatitis C antibodies for at least six months. The patients also had alanine aminotransferase (ALT) levels greater than the upper limit of normal (ULN) — indicating damaged livers — along with detectable serum RNA levels for hepatitis C at the time of the study. The researchers evaluated the immunosuppressive function of the patients’ Tregs at the beginning of the study, 12 weeks into treatment, at the end of treatment, and at the end of each week for 24 follow-up weeks. The Treg immunosuppressive activity was thereby measured by the inhibition ratio of normal T-cell proliferation.

The study’s results revealed that Treg-mediated immunosuppression occurred with an inhibition ratio of 44.45% at the baseline, 18.41% at 12 weeks into treatment, 22.62% at the end of treatment, and 17.46% at the end of follow-ups. Immunosuppression was therefore lower throughout the study’s duration than at the onset. Additionally, Treg-mediated immunosuppression was higher in patients with SVR than in those without SVR at the end of follow-up, with inhibition ratios of 24.20% and 6.87%, respectively.

The results of the study, however, are limited by inconsistent reports regarding Treg frequency in CHC patients. Thus, more work is needed to understand Treg function in the disease. However, Tregs have been known to limit immunopathy by suppressing HCV-specific T-cell responses, and this study successfully showed that combination therapies could be used to decrease the suppression of T-cell proliferation.

 

References:

  1. K. Tseng, et al., Decrease in regulatory T-cell function in chronic hepatitis C patients receiving pegylated-interferon plus ribavirin. International Journal of Infectious Diseases 58, 8-17 (2017),  doi: 10.1016/j.ijid.2017.02.015
  2. http://4.bp.blogspot.com/-dQg4obmWv94/T3d1-7F_tSI/AAAAAAAAHEY/zTLxuNMFRmM/s1600/Scopulariopsis%2Bsp%2B07.jpg
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