Serum IL‑21 levels predict HBeAg decline during rescue therapy in patients with partial response to nucleos(t)ide analogues

Li,Yue; Pan,Calvin Q.; Ji,Shibo; Yan,Gaiqin; Cheng,Jun; Liu,Shunai; Xing,Huichun

doi:10.3892/etm.2021.9648

Serum IL‑21 levels predict HBeAg decline during rescue therapy in patients with partial response to nucleos(t)ide analogues

Authors:
- Yue Li
- Calvin Q. Pan
- Shibo Ji
- Gaiqin Yan
- Jun Cheng
- Shunai Liu
- Huichun Xing
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Affiliations: Department of Hepatology Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China, Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China, Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China
Published online on: January 15, 2021 https://doi.org/10.3892/etm.2021.9648
Article Number: 216
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

To investigate whether IL‑21 levels predict treatment outcomes of salvage therapy among patients with suboptimal response (SOR) to nucleos(t)ide analogues (NAs), serum IL‑21 levels were measured in a prospective cohort of hepatitis B e antigen (HBeAg)‑positive patients with SOR to antiviral therapy. The patients switched therapy to entecavir (ETV) with or without adefovir (ADV) for 104 weeks. IL‑21 levels at treatment week 12 in patients who achieved HBeAg loss with undetectable levels of hepatitis B virus (HBV)‑DNA at week 104 were the primary endpoint and the results were compared with those of corresponding patients without such an endpoint. Furthermore, IL‑21 levels at treatment week 12 in patients who achieved an HBeAg‑level decline at week 104 were assessed as the secondary endpoint. Among 24 enrolled patients with SOR to ADV (n=21), telbivudine (n=2) or ETV (n=1), the median (10‑90th percentile) levels of HBeAg, HBV‑DNA and ALT at baseline were 2.7 (0.2‑3.1) log₁₀ S/CO, 5.2 (3.5‑7.5) log₁₀ IU/ml and 0.9 (0.5‑3.1) upper limit of normal, respectively. Comparison of the patients with and without HBeAg loss at week 104 indicated that their mean IL‑21 levels did not significantly differ at week 12 (63.0±14.4 vs. 55.9±10.5 pg/ml; P=0.26). In the secondary endpoint analyses of patients with and without HBeAg level decline, the elevated levels of IL‑21 at the first 12 weeks were significantly higher in the decline group (15.6±8.3 vs. 3.1±13.2 pg/ml; P=0.03). Following adjustment for confounding factors, the elevated levels of IL‑21 from baseline to week 12 independently predicted an HBeAg level decline at week 104 (odds ratio=1.137, R²=0.23; P=0.047). In conclusion, the serum IL‑21 levels at the first 12 weeks during the salvage therapy independently predicted HBeAg level decline at treatment week 104 in patients with SOR to NAs (ClinicalTrials.gov identifier: NCT01829685; date of registration, April 2013).

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