Reactivation of hepatitis B virus in rheumatoid arthritis patients treated with biological disease-modifying antirheumatic drugs.
OBJECTIVE
To examine the incidence of hepatitis B virus (HBV) reactivation in patients with rheumatoid arthritis (RA) receiving biological disease-modifying antirheumatic drugs (DMARDs).


METHODS
We retrospectively reviewed RA patients treated with biological DMARDs at our institution from July 2010 to December 2012. Patients with antibodies for hepatitis B core antigen and/or hepatitis B surface antigen were regarded as having prior HBV infection. Clinical data on these patients, including HBV-DNA levels, were retrieved from the medical records.


RESULTS
During the study period, 251 patients were administered various biological DMARDs. Six patients with a history of HBV vaccination and one patient with positive HBV surface antigen were excluded from the study. Fifty-seven of the remaining 244 patients (23.4%) had prior HBV infection. These patients were followed for a median of 18 months (range: 2-27 months) and HBV-DNA was examined a median of seven times (range: 2-27). HBV-DNA was detected in three patients (5.3%), comprising two receiving tocilizumab and one receiving etanercept. However, HBV-DNA levels were below the quantitation limit (<2.1 log copies mL(-1) ) in all three patients. HBV-DNA became negative again within several months in all three patients, while biological DMARDs were continued and liver function tests remained normal throughout.


CONCLUSIONS
HBV-DNA reactivation occurred in 5.3% of RA patients with prior HBV infection during treatment with biological DMARDs, but there were no associated clinical manifestations. Accordingly, it seems that biological DMARDs can be used safely in patients with RA.
Division of Rheumatology and Clinical Immunology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
Jun
J
Nakamura
Division of Rheumatology and Clinical Immunology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
Takao
T
Nagashima
Division of Rheumatology and Clinical Immunology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
Katsuya
K
Nagatani
Division of Rheumatology and Clinical Immunology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
Taku
T
Yoshio
Division of Rheumatology and Clinical Immunology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
Masahiro
M
Iwamoto
Division of Rheumatology and Clinical Immunology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
Seiji
S
Minota
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D001688:Biological Products / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006509:Hepatitis B / Q000175:diagnosis / Q000276:immunology / Q000821:virology*; D006510:Hepatitis B Antibodies / Q000097:blood; D006512:Hepatitis B Core Antigens / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D016867:Immunocompromised Host; D007564:Japan; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D019562:Viral Load; D014775:Virus Activation / Q000187:drug effects*
D018501:Antirheumatic Agents; D001688:Biological Products; D015415:Biomarkers; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens
de novo hepatitis; hepatitis B virus; rheumatoid arthritis; tumor necrosis factor