Reactivation of hepatitis B virus infection following rituximab treatment in HBsAg-negative, HBcAb-positive rheumatoid arthritis patients: A long-term, real-world observation

Int J Rheum Dis. 2019 Jun;22(6):1145-1151. doi: 10.1111/1756-185X.13582. Epub 2019 May 22.

Abstract

Aim: Longitudinal data of the reactivation of hepatitis B virus (rHBV) and serial serological markers or HBV-DNA has been limited. This study aimed to investigate the temporal course of rHBV development in rheumatoid arthritis (RA) patients undergoing long-term rituximab therapy.

Methods: The occurrence of rHBV was examined in 157 RA patients during rituximab therapy. Serum levels of HBV surface antigen (HBsAg), HBV core antibody (HBcAb), and HBsAb were determined by electrochemiluminescence immunoassays, and viral loads by real-time polymerase chain reaction assay.

Results: Among 157 patients undergoing rituximab therapy, 103 (65.6%) were HBsAg-negative and HBcAb-positive. Before rituximab therapy, 20 (19.4%) of these 103 patients were HBsAb-negative, while 83 (80.1%) were HBsAb-positive. Five (20%) HBsAb-negative patients developed rHBV after rituximab therapy. Among 83 HBsAb-positive patients, 4 (4.8%) developed rHBV. Among 9 patients with rHBV, 7 (77.7%) exhibited HBsAg seroreversion. Significant decline of HBsAb titers (mean ± SD, 296.0 ± 417.3 mIU/mL at baseline vs 187.0 ± 332.5 mIU/mL after rituximab therapy, P < 0.001) was observed in HBsAg-/HBsAb + patients. All HBsAg-negative patients who developed rHBV during rituximab therapy were characterized by baseline HBsAb titers < 100 mIU/mL and negative HBsAb at the time of rHBV. HBsAb positivity was an independent protective factor for rHBV (hazards ratio: 0.14, 95% CI: 0.03-0.62, P = 0.009).

Conclusion: Baseline HBsAb positivity was a significant protective factor for rHBV in HBsAg-negative, HBcAb-positive RA patients receiving rituximab therapy.

Keywords: HBsAg seroreversion; hepatitis B virus reactivation; rheumatoid arthritis; rituximab therapy.

MeSH terms

  • Aged
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / epidemiology
  • Arthritis, Rheumatoid / immunology
  • Biomarkers / blood
  • Female
  • Hepatitis B / diagnosis
  • Hepatitis B / epidemiology
  • Hepatitis B / immunology
  • Hepatitis B / virology*
  • Hepatitis B Antibodies / blood*
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / immunology
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Recurrence
  • Retrospective Studies
  • Risk Factors
  • Rituximab / adverse effects*
  • Time Factors
  • Treatment Outcome
  • Virus Activation / drug effects*

Substances

  • Biomarkers
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Rituximab