Yi-Ming Chen1,2,3,4, Hsin-Hua Chen1,2,3,4, Wen-Nan Huang3,4, Yi-Hsing Chen3,4, Tsu-Yi Hsieh4,5, Sheng-Shun Yang3,6, Joung-Liang Lan7,8,9, Der-Yuan Chen7,8,9. 1. Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan. 2. Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan. 3. Faculty of Medicine, National Yang Ming University, Taipei, Taiwan. 4. Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan. 5. Department of Medical Education, Taichung Veterans General Hospital, Taichung, Taiwan. 6. Division of Gastroenterology and Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan. 7. Rheumatology and Immunology Center, China Medical University Hospital, Taichung, Taiwan. 8. Translational Medicine Laboratory, Rheumatology and Immunology Center, China Medical University Hospital, Taichung, Taiwan. 9. School of Medicine, China Medical University, Taichung, Taiwan.
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.
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 RApatients 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 RApatients receiving rituximab therapy.