The reduction in CD8+PD-1+ T cells in liver histological tissue is related to Pegylated IFN-α therapy outcomes in chronic hepatitis B patients

BMC Infect Dis. 2020 Aug 10;20(1):590. doi: 10.1186/s12879-020-05320-z.

Abstract

Background: Antiviral therapy is recommended for patients with immune-active chronic hepatitis B (CHB) to decrease the risk of liver-related complications. However, the outcomes of the pegylated IFN-α (PEG-IFN-α) therapy vary among CHB patients. We aimed to identify factors that can influence the outcomes in CHB patients who received antiviral PEG-IFN-α monotherapy.

Methods: Thirty-two CHB patients who received PEG-IFN-α monotherapy were enrolled in this study. All of the patients underwent two liver biopsies at baseline and 6 months after the initiation of the therapy. CD8+ T cells, CD4+ T cells, CD68+ mononuclear cells, and PD-1 levels in the 64 liver biopsy specimens were examined via immunofluorescence.

Results: The overall median frequency of CD8+ T cells in the liver tissues of 32 CHB patients significantly decreased at 6 months after the therapy initiation (p < 0.01). In the FIER (fibrosis and inflammation response with HBeAg seroconversion) group, CD8+PD-1+ T cells significantly decreased at 6 months (p < 0.05), while CD8+PD-1- T cells had no significant difference. On the contrary, in the FIENR (no fibrosis and inflammation response and HBeAg seroconversion) group, CD8+PD-1- T cells significantly decreased after 6 months of PEG-IFN-α treatment (p < 0.05), while CD8+PD-1+ T cells had no significant difference. In addition, the levels of CD68+ mononuclear cells in the FIER group showed an overall increasing trend after treatment (p < 0.05).

Conclusions: The changes in the levels of CD8+PD-1+ T cells and CD68+ mononuclear cells may be related to the response to PEG-IFN-α therapy.

Keywords: CD4+ T cells; CD68+ mononuclear cells; CD8+ T cells; Chronic hepatitis B; PD-1; Pegylated IFN-α.

MeSH terms

  • Adult
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Antiviral Agents / therapeutic use*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • Female
  • Hepatitis B e Antigens / blood
  • Hepatitis B e Antigens / immunology
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Interferon-alpha / therapeutic use*
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / metabolism
  • Liver / metabolism
  • Liver / pathology*
  • Male
  • Polyethylene Glycols / therapeutic use*
  • Programmed Cell Death 1 Receptor / metabolism
  • Recombinant Proteins / therapeutic use
  • Young Adult

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Antiviral Agents
  • CD68 antigen, human
  • Hepatitis B e Antigens
  • Interferon-alpha
  • Programmed Cell Death 1 Receptor
  • Recombinant Proteins
  • Polyethylene Glycols
  • peginterferon alfa-2a