IL-21 Is Associated With Virological Relapse of HBeAg Positive Chronic Hepatitis B After Discontinuance of Entecavir

Turk J Gastroenterol. 2021 Feb;32(2):178-186. doi: 10.5152/tjg.2021.19703.

Abstract

Background: To investigate the association between interleukin-21 (IL-21) expression level and virological relapse (VR) of HBeAg positive chronic hepatitis B (CHB) after discontinuance of entecavir (ETV).

Methods: The serum IL-21 level of 112 CHB patients was measured at 0, 12, 24, 52, and 104 weeks after ETV discontinuance. ELISA was used for the measurement of serum IL-21 level. VR was defined as two continuous examinations with an interval of 1 month with both showing HBV DNA >10 000 copies/mL after drug discontinuance.

Results: The serum IL-21 levels at 0, 12, 24, 52, and 104 weeks after discontinuance of ETV were significantly higher in the durable virological remission (DVR) group than in the VR group (all P < .01). The area under the ROC curve (AUC) was 0.728 (95% CI: 0.630-0.827, P < .001), while the best cut-off value was 49.8 pg/mL. Multivariate Cox model showed that the factors affecting the relapse included age, followed by HBsAg level at the serological conversion of HBeAg and serum IL-21 level (all P < .05).

Conclusion: Serum IL-21 level at ETV discontinuance is an independent risk factor for CHB relapse. IL-21 acts as an immunomodulatory factor in maintaining DVR in HBeAg positive CHB patients after ETV discontinuance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / therapeutic use
  • DNA, Viral
  • Guanine / analogs & derivatives
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens*
  • Hepatitis B virus / genetics
  • Hepatitis B, Chronic* / drug therapy
  • Humans
  • Interleukins
  • Recurrence
  • Treatment Outcome

Substances

  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Interleukins
  • entecavir
  • Guanine
  • interleukin-21

Grants and funding

This study was supported by the Chinese Foundation for Hepatitis Prevention and Control—TianQing Liver Disease Research (grant no.: TQGB2011004), Nanjing Medical University of Science and Technology (grant no.: 2012NJMU072), and Wuxi Technology Development Fund (grant no.: 2013CSE31N1318).