结果：共入组105例HBeAg阳性CHB患者，其中100例完成了48周的ETV治疗和随访。治疗48周后，7例患者乙肝s抗原（HBsAg）下降≥1 log10，但无一例患者HBsAg消失。 13例患者血清学HBeAg消失，3例患者血清学HBeAg转变。病毒学完全缓解组基线HBsAg和HBeAg水平、HBV DNA载量、IL-10、TGF-β1水平低于病毒学不完全缓解组，而病毒学完全缓解组ALT水平高于病毒学完全缓解组。在不完全病毒学反应组中。单变量分析和多变量分析均显示基线生化指标、病毒学指标和细胞因子水平与48周时的完全病毒学应答无相关性。在多变量分析中，低基线 HBV DNA 载量以及 HBeAg 和 IL-10 水平与 ETV 治疗 48 周后 ALT 正常化显着相关（HBeAg OR = 1.003，95% CI 1.001-1.006，p = 0.007；HBV DNA OR = 0.184, 95% CI 0.046-0.739, p = 0.017；IL-10 OR = 0.040, 95% CI 0.972-0.999, p = 0.040)。
结论：细胞因子水平在 ETV 抗病毒治疗期间发生动态变化。 ETV 治疗 48 周后，低基线 HBV DNA 载量、HBeAg 和 IL-10 水平与 ALT 正常化显着相关。
Dynamic changes of cytokine profiles and virological markers during 48 weeks of entecavir treatment for HBeAg-positive chronic hepatitis B
Minghui Li 1 2 , Yuanjiao Gao 1 , Liu Yang 1 , Yanjie Lin 2 , Wen Deng 1 , Tingting Jiang 1 , Xiaoyue Bi 1 , Yao Lu 1 , Lu Zhang 1 , Ge Shen 1 , Ruyu Liu 1 , Shuling Wu 1 , Min Chang 1 , Mengjiao Xu 1 , Leiping Hu 1 , Rui Song 3 , Yuyong Jiang 4 , Wei Yi 5 , 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
Department of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
4
Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
5
Department of Gynecology and Obstetrics, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Objective: The aims of this study were to investigate the kinetic changes of serum, virological, and immunological markers during entecavir (ETV) antiviral therapy and to explore whether these indicators can predict the antiviral efficacy of ETV in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients.
Methods: HBeAg-positive CHB patients were enrolled and treated with ETV 0.5 mg/day. Clinical biochemical, virological, and serological tests were performed at baseline and every 12 weeks during the 48-week treatment. Plasma levels of cytokines (Flt-3L, IFN-α2, IFN-γ, IL-10, IL-17A, IL-6, TGF-β1, TGF-β2, TGF-β3, and TNF-α) were measured at baseline and at 12 and 24 weeks after treatment. Analysis of the trends of these clinical indicators in ETV antiviral therapy was performed.
Results: A total of 105 HBeAg-positive CHB patients were enrolled, and 100 of them completed 48 weeks of ETV treatment and follow-up. After 48 weeks of treatment, hepatitis B s antigen (HBsAg) decline ≥ 1 log10 was found in seven patients, but no patient achieved HBsAg disappearance. serological HBeAg disappeared in 13 patients, and serological HBeAg transformed in 3 patients. The baseline HBsAg and HBeAg levels, HBV DNA load, IL-10, and TGF-β1 levels in the complete virological response group were lower than those in the incomplete virological response group, while the ALT level in the complete virological response group was higher than that in the incomplete virological response group. Both univariate analysis and multivariate analysis showed that baseline biochemical indexes, virological indexes, and cytokine levels had no correlation with the complete virological response at 48 weeks. In multivariate analysis, low baseline HBV DNA load, and HBeAg and IL-10 levels were significantly associated with ALT normalization after 48 weeks of ETV treatment (HBeAg OR = 1.003, 95% CI 1.001-1.006, p = 0.007; HBV DNA OR = 0.184, 95% CI 0.046-0.739, p = 0.017; IL-10 OR = 0.040, 95% CI 0.972-0.999, p = 0.040).
Conclusion: Cytokine levels changed dynamically during ETV antiviral therapy. Low baseline HBV DNA load, and HBeAg and IL-10 levels were significantly associated with ALT normalization after 48 weeks of ETV treatment.
Keywords: chronic hepatitis B; cytokines; deoxyribose nucleic acid; entecavir; hepatitis B e antigen.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The editor declared a shared parent affiliation with the authors at the time of review. 作者: StephenW 时间: 2022-10-9 20:38