Research Article
High serum IL-21 levels after 12 weeks of antiviral therapy predict HBeAg seroconversion in chronic hepatitis B- Shi-Wu Ma1, 2, †,
- Xuan Huang1, †,
- 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, ,
- 1 Hepatology Unit and Key Lab for Organ Failure Research, Nanfang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Guangzhou 510515, China
- 2 Department of Infectious Diseases, Kunming General Hospital of PLA, Kunming 650032, China
- 3 Department of Infectious Diseases, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, China
- 4 The New Zealand Liver Transplant Unit, Auckland City Hospital, Private Bag 92-024, Auckland, New Zealand
- 5 Novatis Pharma AG, Basel, Switzerland
- Available online 13 December 2011. See Editorial, pages 753–755.
Background & AimsInterleukin-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. MethodsSerum 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. ResultsMedian 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. ConclusionsSerum 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.
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