title: Manipulation of Regulatory Cells' Responses to Treatments for Chronic Hepatitis B Virus Infection.
abstract: BACKGROUND
  Identification of effective treatments in hepatitis B virus (HBV) infection remains a controversial topic. Although the currently approved drugs for HBV control the disease's progression and also limit associated outcomes, these drugs may not fully eradicate HBV infection. In addition to better managing patients with chronic hepatitis B (CHB) infection, the induction of seroclearance by these drugs has been a commonly discussed topic in recent years.
  
  
  OBJECTIVE
  In this study, we focused on treating CHB infection via the manipulation of T cells' responses to identify possible approaches to cure CHB.
  
  
  METHODS
  All studies relevant to the role of cellular and humoral responses in HBV infection (especially regulatory cells) were investigated via a systematic search of different databases, including PubMed, Scopus, and Google Scholar. Considering extracted data and also our unpublished data regarding the association between regulatory cytokines and CHB, we introduced a novel approach for the induction of seroclearance.
  
  
  RESULTS
  Considering the increased levels of regulatory cytokines and also regulatory T cells (Tregs) during CHB, it seems that these cells are deeply involved in CHB infection. The inhibition of regulatory T cells may reverse the dysfunction of effector T cells in patients with CHB infection. In order to inhibit Tregs' responses, different types of approaches could be employed to restore the impaired function of effector T cells. The blockade of IL-10, IL-35, CTLA-4, PD-1, and TIM-3 were discussed throughout this study. Regardless of the efficacy of these methods, CHB patients may experience serious liver injuries due to the cytotoxic action of CD8+ T cells. Antiviral therapy and a decrease in HBV DNA to undetectable levels could also significantly reduce the risk of the hepatitis B flare.
  
  
  CONCLUSIONS
  The inhibition of Tregs is a novel therapeutic approach to cure chronically HBV infected patients. However, further studies are needed to investigate the safety and efficacy of this approach.
authors.affiliation: Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqyiatallah University of Medical Sciences, Tehran, IR Iran.
authors.forename: Soheil
authors.initials: S
authors.lastname: Tavakolpour
authors.affiliation: Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqyiatallah University of Medical Sciences, Tehran, IR Iran.
authors.forename: Seyed Moayed
authors.initials: SM
authors.lastname: Alavian
authors.affiliation: Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Sali
keywords: Chronic Hepatitis B; Hepatitis B Viruses; Regulatory T Cells; T-Lymphocytes; Treg Cells