Treatment cessation in HBeAg-negative chronic hepatitis B: clinical response is associated with increase in specific proinflammatory cytokines

Sci Rep. 2023 Dec 18;13(1):22590. doi: 10.1038/s41598-023-50216-y.

Abstract

Patients with HBeAg-negative chronic hepatitis B may experience an immune response after stopping nucleos(t)ide analogue (NA)therapy, which may potentially trigger HBsAg loss or off-therapy sustained viral control. The immunological mechanisms determining clinical response remain poorly understood. To identify inflammatory signatures associated with defined outcomes, we analysed plasma cytokines and chemokines from 57 HBeAg-negative patients enrolled in the Nuc-Stop Study at baseline and 12 weeks after NA cessation. Clinical response at 12 weeks was classified into four groups: immune control, viral relapse, evolving clinical relapse, and resolving clinical relapse. Twelve weeks after treatment cessation 17 patients (30%) experienced immune control, 19 (33%) viral relapse, 6 (11%) evolving clinical relapse, and 15 (26%) resolving clinical relapse. There was a significant increase in interferon-γ-induced protein 10 (IP-10; p = 0.012) and tumor necrosis factor (TNF; p = 0.032) in patients with evolving clinical relapse. Sparse partial least-squares multivariate analyses (sPLS-DA) showed higher first component values for the clinical relapse group compared to the other groups, separation was driven mainly by IP-10, TNF, IL-9, IFN-γ, MIP-1β, and IL-12. Our results demonstrate that evolving clinical relapse after NA cessation is associated with a systemic increase in the proinflammatory cytokines IP-10 and TNF.Clinical trial registration: ClinicalTrials.gov, Identifier: NCT03681132.

MeSH terms

  • Antiviral Agents / therapeutic use
  • Chemokine CXCL10
  • Cytokines / therapeutic use
  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Hepatitis B virus / genetics
  • Hepatitis B, Chronic*
  • Humans
  • Recurrence
  • Treatment Outcome
  • Withholding Treatment

Substances

  • Hepatitis B e Antigens
  • Cytokines
  • Chemokine CXCL10
  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Surface Antigens

Associated data

  • ClinicalTrials.gov/NCT03681132