Interferon therapy-induced reduction in PD-1 + CD8 + and CD160 + CD8 + T cells is associated with functional cure in hepatitis B.

[BACKGROUND AND AIMS] HBsAg seroclearance is a key indicator of functional cure in chronic HBV. We evaluated the efficacy of pegylated interferon-α (Peg-IFN-α) in HBeAg-negative patients and its association with T-cell subsets.

[METHODS] We retrospectively analyzed 618 patients, 34 of whom underwent longitudinal immune profiling.

[RESULTS] Among 618 patients, a total of 214 cases (34.6%) achieved HBsAg clearance, namely 214 cases in group R and 404 cases in group NR. The R group was younger, had longer treatment, and had lower baseline HBsAg levels compared to the NR group. In 34 HBeAg-negative patients with chronic HBV infection, we studied the distribution of CD4 + and CD8 + T cells at different stages of differentiation. After 24 weeks of interferon therapy, responders exhibited increased CD4 + TCM and stable CD8 + TCM levels, along with decreased CD8 + TEMRA and Th2 cells. In contrast, non-responders showed reductions in TCM, elevated TEMRA, and Th2 cells. Responders exhibited a marked decline in PD-1 + CD8 + and CD160 + CD8 + T cells (at 0.97 and 0.95 times the baseline), whereas non-responders showed relative increases (at 1.74 and 1.55 times the baseline).

[CONCLUSION] Peg-IFN-α may promote HBsAg clearance in selected HBeAg-negative patients with low antigen burden and partially reversible T-cell exhaustion.