Risk of Reverse Seroconversion of Hepatitis B Virus Surface Antigen in Rituximab-Treated Non-Hodgkin Lymphoma Patients: A Large Cohort Retrospective Study.
Rituximab causes hepatitis B virus (HBV) reactivation in HBV surface antigen (HBsAg)-seronegative patients with CD20-positive B-cell non-Hodgkin lymphoma (CD20 NHL), especially for those seropositive to the antibody of core antigen (anti-HBc). Clinical hepatitis usually develops after reverse seroconversion of HBsAg (HBV-RS), indicated by the reappearance of HBsAg in serum. Because of the relatively high prevalence of anti-HBc seropositivity in unvaccinated HBsAg-seronegative adults in an HBV hyperendemic area, we aimed to investigate additional factors influencing the development of rituximab-associated HBV-RS.Between January 2000 and December 2010, unvaccinated HBsAg-seronegative adults with CD20 NHL who had received rituximab-containing therapy but not anti-HBV agents were enrolled. Patients with and without HBV-RS were compared in terms of clinical factors and treatments including the number of cycles of rituximab therapy, and transplantation. Competing risk regression was used to identify the factors associated with HBV-RS.For the 482 patients enrolled, the serological status of anti-HBc was available in 75.9%, with a seropositivity rate of 86.6%. At the last follow-up, a total of 33 (6.85%) patients had HBV-RS, with 95.8% anti-HBc seropositive, 78.9% anti-HBs seropositive, and none anti-HCV seropositive. HBV-RS patients have received more cycles (≥6) and prolonged durations of rituximab therapy, and hematopoietic stem cell transplantation. The overall survival was not different between patients with and those without HBV-RS. At the time of HBV-RS, a total of 25 (78.1%) patients had hepatitis flare, especially when HBV-RS appeared during/after induction therapy (100%, 10 of 10). Three (9.1%) patients had fulminant hepatitis, resulting in death in 1 (3%) patient. A higher rituximab cycle intensity was associated with a higher rate of hepatitis flare at the time of HBV-RS. When death in the absence of HBV-RS was considered as the competing risk, the univariate and multivariate regression analyses showed that several factors were independently associated with the development of HBV-RS, including anti-HCV seronegativity, histological subtype of posttransplant lymphoproliferative disorders, ≥6 cycles of rituximab therapy, and succeeding hematopoietic stem cell transplantation.The findings of our study identify additional factors influencing the development of rituximab-associated HBV-RS in HBsAg-seronegative adults with CD20 NHL.
From the Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital (L-TH, J-PG, Y-BY, C-YL, J-HL, P-MC, C-HT, M-HY); Institute of Clinical Medicine, National Yang-Ming University School of Medicine (L-TH, T-JC, J-PG, C-FY, Y-BY, C-YL, J-HL, P-MC, C-HT, M-HY, Y-HH); Division of Transfusion Medicine, Department of Medicine (T-JC); Department of Pathology and Laboratory Medicine (C-FY); Division of Microbiology, Department of Pathology and Laboratory Medicine (Y-JC); Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital (Y-JC); Institute of Public Health, National Yang-Ming University (Y-JC); and Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital (Y-HH), Taipei, Taiwan.
Liang-Tsai
LT
Hsiao
Tzeon-Jye
TJ
Chiou
Jyh-Pyng
JP
Gau
Ching-Fen
CF
Yang
Yuan-Bin
YB
Yu
Chun-Yu
CY
Liu
Jin-Hwang
JH
Liu
Po-Min
PM
Chen
Cheng-Hwai
CH
Tzeng
Yu-Jiun
YJ
Chan
Muh-Hwa
MH
Yang
Yi-Hsiang
YH
Huang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D000069283:Rituximab; D013624:Taiwan / Q000453:epidemiology
D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D006514:Hepatitis B Surface Antigens; D000069283:Rituximab