Expression of Functional Molecule on Plasmacytoid Dendritic Cells Is Associated With HBsAg Loss in HBeAg-Positive Patients During PEG-IFN α-2a Treatment

Abstract

ObjectiveThe ideal endpoint of antiviral therapy in chronic hepatitis B (CHB) patients is to clear hepatitis B surface antigen (HBsAg). This study aimed to evaluate whether the expression of functional molecules on plasmacytoid dendritic cells (pDCs) is associated with HBsAg loss in HBeAg-positive patients during peginterferon alpha-2a (PEG IFN α-2a) therapy.MethodsA single-center prospective cohort study was performed in HBeAg-positive CHB patients who were treated with PEG-IFN α-2a and followed up for 4 years. HBsAg clearance, HBeAg loss and undetectable HBV DNA achieved by PEG-IFN α-2a therapy was considered as functional cure. The frequencies of pDC and CD86+ pDC in peripheral blood, and the mean fluorescence intensity of CD86 (CD86MFI) on the surface of pDC were measured at starting therapy, after 12 and 24 weeks of therapy.ResultsOf 63 patients enrolled, 17 patients achieved HBsAg loss. The baseline HBV DNA load in Non-functional-cure group was significantly higher than that in Functional cure group, and the CD86+ pDC% was significantly lower in patients without functional cure. HBV DNA load (OR=0.146, P = 0.002) and CD86+ pDC% (OR=1.183, P = 0.025) were independent factors associated with functional cure confirmed by binary logistic regression analysis. In the Functional cure group, HBsAg, HBeAg, and HBV DNA loads decreased remarkably after 12 weeks and 24 weeks of treatment compared to baseline. In Non-functional-cure group, CD86+ pDC% and CD86MFI increased significantly from baseline after 12 weeks of treatment. In the Functional cure group, compared with baseline, pDC% increased significantly at 24 weeks, while CD86MFI increased significantly after 24 weeks of treatment.ConclusionThe lower the baseline HBV DNA load and the more the baseline CD86+ pDC%, the easier it is for patients to obtain functional cure.

The relation of the frequency and functional molecules expression on plasmacytoid dendritic cells to postpartum hepatitis in women with HBeAg-positive chronic hepatitis B virus infection

“…Our previous study on the immune function of HBeAg positive chronic hepatitis B patients found that the frequency of pDCs was related to the incidence of CHB, the lower the frequency of pDCs in CHB patients, the more likely they were to develop hepatitis. However, we did not distinguish immature pDCs and mature pDCs frequency changes on the impact of hepatitis in this study ( 7 , 22 ). Our previous retrospective study and this prospective study both suggest that postpartum liver dysfunction is common in women with chronic HBV infection, we also found that the abnormal liver function of HBV infected women mainly occurred in 6-12 weeks postpartum ( 23 , 24 ), which indicated the importance of preventing postpartum hepatitis.…”

Immune response and treatment targets of chronic hepatitis B virus infection: innate and adaptive immunity

“…The TLR9, MyD88, and NF-κB in PDCs are significantly downregulated, type I IFN level is decreased, and immune function is defective ( Zhu et al., 2021 ). The increased frequency of PDCs and high expression of CD86 after treatment help achieve a functional cure ( Cao et al., 2022 ). HBV also induces DCs to produce IL-10, which in turn mediates immune tolerance.…”

Involvement of inflammatory responses in the brain to the onset of major depressive disorder due to stress exposure

“…The IFN therapy has been established as a useful treatment for many diseases such as hepatitis C, hepatitis B, and multiple myeloma (Ettari et al, 2016;Ye and Chen, 2021;Cao et al, 2022;Liu, H. et al, 2022). However, IFN-I treatment is known to induce various neuropsychiatric symptoms, and depression is known to occur at a high frequency of 30% or more (Tovey and Lallemand, 2010;Pinto and Andrade, 2016;Liu et al, 2020).…”