Interferon Therapy-Induced Reduction in PD-1+ CD8+ and CD160+ CD8+ T
Cells Promotes Functional Cure in Hepatitis B
Abstract
Background and Aims: HBsAg seroclearance is a key marker of
functional HBV cure, with Peg-IFN-ɑ-induced elimination closely linked
to T lymphocyte responses. This study evaluates the efficacy of
Peg-IFN-ɑ in HBeAg-negative chronic HBV infection and correlates change
in T lymphocyte subsets expressing inhibitory receptors with achieving
functional cure post-treatment. Methods: From January 2008 to
February 2023, HBeAg-negative chronic HBV patients at Beijing You’an
Hospital were treated with Peg-IFN-ɑ alone or nucleoside analogs.
Patients were categorized into HBsAg response (R) and non-response (NR)
groups based on HBsAg seroclearance. Changes in T lymphocytes expressing
inhibitory receptors were detected by flow cytometry before treatment,
at 12 weeks, and 24 weeks, and correlated with functional cure.
Results: 618 patients were enrolled. The response group was
younger (39 vs. 42 years), had longer treatment (63 vs. 49 weeks), and
had lower baseline HBsAg levels (1.42 vs. 2.18 log10 IU/mL) than the
non-response group. The response group had sustained HBsAg decrease and
higher HBV DNA inhibition and HBsAg seroconversion rates. Compared to
baseline, after 24 weeks of treatment, CD4+ (P=0.044*) and CD8+ central
memory T-cell (TCM) (P=0.022*) frequencies increased in the response
group and decreased in the non-response group. Th2 cell frequency
decreased in the response group and increased in the non-response group,
P=0.013*. PD-1+CD8+T and CD160+CD8+T cell frequencies were significantly
reduced in the response group compared to baseline (P=0.005**, 0.016*),
while the non-response group showed an increase. Conclusion:
Reduced PD-1+CD8+ and CD160+CD8+ T cell frequencies favored functional
hepatitis B cure. Restoration of T-cell function is crucial for a
functional cure of hepatitis B, highlighting the importance of exploring
immunotherapy strategies for HBV infection.