An Immuno-Clinic score model for evaluating T cell immunity and predicting early antiviral therapy effectiveness in chronic hepatitis B

Aging (Albany NY). 2020 Dec 26;12(24):26063-26079. doi: 10.18632/aging.202274. Epub 2020 Dec 26.

Abstract

We generated an Immuno-Clinic score (ICS) model to evaluate T cell immunity based on the clustering of antiviral cytokines and inhibitory molecules in 229 naïve chronic hepatitis B (CHB) patients. 126 patients receiving antiviral therapy were used to validate the model for predicting antiviral therapy effectiveness. Through receiver-operator characteristic curve analysis, the area under the curve, sensitivity, and specificity of the ICS model were 0.801 (95%CI 0.703-0.900), 0.727, and 0.722, respectively. The cut-off value was 0.442. Re-evaluation of T cell immunity in different phases of CHB showed that patients in the immune tolerant phase had the lowest percentage of ICS-high (15%), while patients in the inactive carrier phase had the highest percentage of ICS-high (92%). Patients in the immune active and gray zone phases had 17% and 56% ICS-high, respectively. Elevation of ICS as early as four weeks after treatment could predict the effectiveness of hepatitis B virus (HBV) DNA loss and normalization of alanine aminotransferase, while eight weeks after treatment could predict HBV surface antigen decline. Thus, this ICS model helps clinicians choose an optimal time for initiating antiviral therapy and predicting its efficacy.

Keywords: Immuno-Clinic score (ICS); T-cell; chronic hepatitis B (CHB); cytokines; hepatitis B virus (HBV).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / immunology
  • Antiviral Agents / therapeutic use*
  • Area Under Curve
  • CTLA-4 Antigen / immunology
  • Clinical Decision Rules
  • Cytokines / immunology*
  • DNA, Viral / blood
  • Early Medical Intervention
  • Female
  • Hepatitis A Virus Cellular Receptor 2 / immunology
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / immunology*
  • Humans
  • Immunophenotyping
  • Interferon-gamma / immunology
  • Interleukin-2 / immunology
  • Lymphocyte Activation Gene 3 Protein
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor / immunology
  • ROC Curve
  • Receptors, Immunologic / immunology
  • T-Lymphocytes / immunology*
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Antigens, CD
  • Antiviral Agents
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Cytokines
  • DNA, Viral
  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • Hepatitis B Surface Antigens
  • IL2 protein, human
  • Interleukin-2
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, Immunologic
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • leukocyte-associated immunoglobulin-like receptor 1
  • Interferon-gamma
  • Lymphocyte Activation Gene 3 Protein
  • Lag3 protein, human