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.