Dynamic Changes of Cytokine Profiles and Virological Markers Associated With HBsAg Loss During Peginterferon Alpha-2a Treatment in HBeAg-Positive Chronic Hepatitis B Patients
Minghui Li 1 2 , Luxue Zhang 3 , Si Xie 4 , Fangfang Sun 1 , Zhan Zeng 2 , Wen Deng 1 , Tingting Jiang 1 , Xiaoyue Bi 1 , Yanjie Lin 2 , Liu Yang 1 , Yao Lu 1 , Ge Shen 1 , Ruyu Liu 1 , Shuling Wu 1 , Min Chang 1 , Leiping Hu 1 , Jianping Dong 5 , Wei Yi 6 , Yao Xie 1 2
Affiliations
Affiliations
1
Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
2
Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China.
3
Infectious Disease Department, Xuanwu Hospital, Capital Medical University, Beijing, China.
4
Division of Hepatology, Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
5
Department of Infectious Diseases, Haidian Hospital, Beijing Haidian Section of Peking University Third Hospital, Beijing, China.
6
Department of Gynecology and Obstetrics, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Objective: 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.
Methods: 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.
Results: 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, P < 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, P< 0.001; HBV DNA 4.49 vs.3.13 log10IU/ml, Z=-3.053, P=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, P=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 log10IU/ml, Z=-4.535, P< 0.001; HBeAg 1.48 vs. 13.72 S/CO, Z = 2.512, P = 0.012; Flt3-l 0.00 vs 2.24 pg/ml, Z = 3.137, P=0.002; IL-10 0.70 vs. 2.71 pg/ml, Z=-4.067, P < 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, P < 0.001).
Conclusion: Dynamic changes of cytokines and virology markers during early PEG IFN α-2a treatment were associated with HBsAg loss in HBeAg-positive CHB patients.