High serum IL-21 levels after 12 weeks of antiviral therapy predict HBeAg seroconversion in chronic hepatitis B

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• 作者：Shi-Wu Ma¹ ; ² ; ^&dagger ; ; Xuan Huang¹ ; ^&dagger ; ; Yong-Yin Li¹ ; Li-Bo Tang¹ ; Xiao-Feng Sun³ ; Xiao-Tao Jiang¹ ; Yue-Xin Zhang³ ; Jian Sun¹ ; Zhi-Hua Liu¹ ; William G.H. Abbott¹ ; ⁴ ; Yu-Hong Dong⁵ ; Nikolai V. Naoumov⁵ ; Jin-Lin Hou¹ ; ^{jlhousmu@yahoo.com.cn}
• 关键词：ALT ; alanine aminotransferase ; anti-HBe ; hepatitis B e antibody ; APC ; allpophycocyanin ; CBA ; cytometry beads array ; CHB ; chronic hepatitis B ; Cy7 ; cyanin 7 ; CR ; complete response ; ELISA ; enzyme linked immunosorbent assay ; FITC ; fluorescein isothiocyanate
• 刊名：Journal of Hepatology
• 出版年：2012
• 期刊代码：162_01688278
• 类别：med
• 出版时间：April, 2012
• 卷：56
• 期：4
• 页码：775-781
• 文件大小：791 K

摘要

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Background & Aims

Interleukin-21 (IL-21) stimulates T cell and B cell responses and plays a role in control of chronic viral infections. The role of IL-21 in chronic hepatitis B virus (HBV) infection is not understood.

Methods

Serum IL-21 levels were measured by enzyme immunoassay in 75 HBeAg-positive chronic hepatitis B (CHB) patients undergoing telbivudine treatment. The findings were validated in 103 patients from a separate clinical trial of telbivudine. A complete response to telbivudine was defined as having both HBeAg seroconversion and serum HBV-DNA level <300 copies/ml by treatment week 52. The proportions of T-cells producing IL-21 and/or expressing programmed death 1 (PD-1) in peripheral blood mononuclear cells were assessed longitudinally during treatment by intracellular cytokine staining and flow cytometry.

Results

Median serum IL-21 levels at treatment week 12 were significantly higher in patients who did achieve vs. patients who did not achieve a complete response in both the initial (128.4 vs. 69.2 pg/ml, p = 0.003) and the validation (142.2 vs. 89.9 pg/ml, p = 0.004) trials. Serum levels of IL-21 (p = 0.005) or HBV-DNA (p = 0.003) levels at treatment week 12 independently predicted HBeAg seroconversion in the first year of treatment. The decrease in PD-1 expression on CD4⁺ and CD8⁺ T cells during the first 12 weeks on telbivudine treatment was not correlated with changes in IL-21 concentrations.

Conclusions

Serum IL-21 levels may be a biomarker for HBeAg seroconversion, and may contribute to individualization of antiviral therapy in HBeAg-positive CHB. IL-21 may also have a role in immunotherapy for CHB.