“Immune-tolerant” — a misnomer for HBV infection

When hepatitis B virus (HBV) infection occurs in the perinatal period, often the result is high levels of  HBV DNA yet immune-mediated damage of the infected liver is generally not observed and serum aminotransferases are normal.  This phase of infection has been considered “immune-tolerant.”  This phase can last for years or even decades.  New data indicate that the during this phase, there is preserved T-cell function and there are indications of good immune function (Gastroenterol 2012; 143: 637-45, & editorial 529-32).

The authors of the study isolated T cells from different age groups of patients with chronic HBV infection.  Then, they used flow cytometry methods to measure production of numerous cytokines.  In addition, markers of T-cell exhaustion or inhibition were examined.

Key Finding: young patients had more specific HBV-specific T cells with the ability to proliferate and produce cytokines than adult patients.

The study itself is highly technical with graphs of cytokine profiles, quantitation of T-cell expressing exhaustion markers, dot plots, etc.  Some of the figures are easy to understand like Figure 5 which plots the multifunctionality of HBV-specific response with three separate charts lined up; these correspond to “Immune tolerant,” “Chronic active,” and “Inactive carriers.”

The editorial is essential to understanding this study & restates the other findings:

  • “the authors found that T cells from CHB patients were more likely to produce TH1 cytokines …compared with those from healthy subjects”
  • they “found no global differences in this profile between tolerant and active states”
  • HBV-specific T-cell response: “a PD-1 high/CD127 low ‘exhausted’ phenotype were actually found to increase with age”
  • “T-cell responses to HBV core, envelope, and X proteins were readily observable in all patients”

The editorial speculates that so-called ‘tolerance’ may occur at a local/hepatic level, largely a ‘matter of sequestration.’  And, concludes that this study has “view-changing” observations.  Ultimately, this may lead to therapeutic treatments aimed at the liver microenvironment & may change our opinion of the suitability of treating younger patients.

6 thoughts on ““Immune-tolerant” — a misnomer for HBV infection

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