Changes of cytokine levels and T cell surface molecules in patients with chronic hepatitis B and the association with functional cure

BACKGROUND This study aimed to examine changes in levels of cytokine and T cell surface molecules in chronic hepatitis B (CHB) patients receiving sequential interferon therapy following 1-year nucleos(t)ide analogues (NAs) treatment. METHODS Cytokine levels were measured in 30 patients, and T cell surface molecule expression was measured in 48 patients receiving sequential interferon therapy and 24 patients only receiving NA mono-therapy. A HBsAg titer of < 0.05 IU/ml was defined as a "functional cure". RESULTS In the cured group (HBsAg < 0.05 IU/ml), a decreasing probability was observed in IFN-γ (after week 0), and IL-22 and IP-10 (after week 12). In the non-cured group (HBsAg ≥ 0.05 IU/ml), a probability of slightly decreasing was observed for IFN-γ (after week 12), and a probability of increasing IP-10 concentration (after week 0) was observed. GEE analyses showed significant differences in the levels of IL-10, IL-23, CCL-3, IL-1β, IL-2, and IL-12P70 between the two groups. In GEE analysis, there were significant differences in expressions of CD45RO+ between the cured group and the non-cured group. The frequencies of T cells expressing Tim-3, CD62L, and CD152 were significantly lower in the sequential interferon therapy group than in the NA mono-therapy group. CONCLUSIONS Changes in cytokine levels (IFN-γ, IP-10, IL-10, IL-23, CCL-3, IL-1β, IL-2, and IL-12P70) and T cell surface molecules (CD45RO+) may predict HBsAg seroconversion in CHB patients receiving sequential interferon therapy. The period from week 12 to week 24 during sequential interferon therapy may be a critical time of immune status change. This article is protected by copyright. All rights reserved.