AUTHOR=Li Minghui , Zhang Luxue , Xie Si , Sun Fangfang , Zeng Zhan , Deng Wen , Jiang Tingting , Bi Xiaoyue , Lin Yanjie , Yang Liu , Lu Yao , Shen Ge , Liu Ruyu , Wu Shuling , Chang Min , Hu Leiping , Dong Jianping , Yi Wei , Xie Yao 

TITLE=Dynamic Changes of Cytokine Profiles and Virological Markers Associated With HBsAg Loss During Peginterferon Alpha-2a Treatment in HBeAg-Positive Chronic Hepatitis B Patients

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.892031

DOI=10.3389/fimmu.2022.892031

ISSN=1664-3224

ABSTRACT=<sec><title>Objective</title><p>To explore dynamic changes of cytokines and virological markers associated with hepatitis B surface antigen (HBsAg) loss during peginterferon alpha-2a (PEG-IFN α-2a) treatment in hepatitis B e antigen (HBeAg) positive chronic hepatitis B (CHB) patients.</p></sec><sec><title>Methods</title><p>It was a single-center prospective cohort study. HBeAg-positive CHB patients were prospectively and consecutively enrolled. Cytokines were detected at baseline, week 12 and 24 of PEG-IFN treatment. HBsAg disappearance rate was the primary evaluation index at 48 weeks of PEG-IFN treatment.</p></sec><sec><title>Results</title><p>Among 100 patients who completed the 48-week PEG-IFN α-2a treatment, 38 patients achieved serum HBeAg disappearance, 25 patients achieved HBeAg seroconversion, 9 patients achieved functional cure, 37 patients had HBsAg decline of ≥1 log IU/ml, and 8 patients produced hepatitis B surface antibody (HBsAb). Albumin (ALB), fms-like tyrosine kinase 3 ligand (FLT3-L) and interferon-alpha2 (IFN-α2) in the clinical cure group were significantly lower than those in the non-clinical-cure group at baseline. After 12 weeks of treatment, HBsAg in the clinical cure group was significantly lower than that in the non-clinical-cure group (median 1.14 vs. 3.45 log10IU/ml, Z=-4.355, <italic>P</italic> &lt; 0.001). The decrease of HBsAg and hepatitis B virus desoxyribose nucleic acid (HBV DNA) in the clinical cure group was significantly higher than that in non-clinical-cure group (median: HBsAg 1.96 vs. 0.33 log10IU/ml, Z=-4.703, <italic>P</italic>&lt; 0.001; HBV DNA 4.49 vs.3.13 log<sub>10</sub>IU/ml, Z=-3.053, <italic>P</italic>=0.002). The increase of IFN-α2 in the cure group was significantly higher than that in the non-clinical-cure group (497.89 vs. 344.74, Z=-2.126, <italic>P</italic>=0.034). After 24 weeks of treatment, HBsAg, HBeAg, Flt3-L, and IL-10 in the clinical cure group were significantly lower than those in the non-clinical-cure group (median: HBsAg 0.70 vs. 3.15 log<sub>10</sub>IU/ml, Z=-4.535, P&lt; 0.001; HBeAg 1.48 vs. 13.72 S/CO, Z = 2.512, <italic>P</italic> = 0.012; Flt3-l 0.00 vs 2.24 pg/ml, Z = 3.137, <italic>P</italic>=0.002; IL-10 0.70 vs. 2.71 pg/ml, Z=-4.067, <italic>P</italic> &lt; 0.001). HBsAg decreased significantly in the clinical cure group compared with non-clinical-cure group (median 3.27 vs. 0.45, Z=-4.463, <italic>P</italic> &lt; 0.001).</p></sec><sec><title>Conclusion</title><p>Dynamic changes of cytokines and virology markers during early PEG IFN α-2a treatment were associated with HBsAg loss in HBeAg-positive CHB patients.</p></sec>