Prospective study of reactivation of hepatitis B virus in patients with rheumatoid arthritis who received immunosuppressive therapy: evaluation of both HBsAg-positive and HBsAg-negative cohorts.
BACKGROUND
Screening and prophylactic treatment for hepatitis B virus (HBV) reactivation is recommended for patients who receive immunosuppressive or cytotoxic therapy. The aim of this study was to clarify the prevalence of HBV reactivation in rheumatoid arthritis (RA) patients who had received more than 1 year of immunosuppressive therapy. This study also evaluated guidelines for determining HBV reactivation in patients with RA.


METHODS
This was a prospective non-randomized, non-controlled study. We enrolled 50 patients with RA who had antibodies against hepatitis B core antigen (anti-HBc) and who had started treatment with disease-modifying anti-rheumatic drugs, including those who had additionally received anti-tumor necrosis factor-α (anti-TNF-α). HBV DNA levels were measured every 2-3 months by a real-time, polymerase chain reaction-based method. Entecavir was administered to patients with HBV DNA levels >2.1 log/ml.


RESULTS
The mean observation period was 23 months (range 12-32 months). HBV reactivation occurred in 2 of 5 patients with HBV surface antigen (HBsAg) and in 1 of 45 patients without HBsAg. In patients who received anti-TNF-α therapy, antibodies against HBsAg decreased significantly. Entecavir therapy inhibited HBV amplification and prevented HBV-associated flares of hepatitis.


CONCLUSIONS
The incidence of HBV reactivation was low in RA patients in whom HBV infection had been resolved. Screening for HBV reactivation and prophylactic therapy with entecavir were effective means of preventing HBV-associated hepatic failure in patients with HBsAg, as well as in those with only anti-HBc who received immunosuppressive therapy for RA.
Department of Hepatology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan. atamori@med.osaka-cu.ac.jp
Akihiro
A
Tamori
Tatsuya
T
Koike
Hitoshi
H
Goto
Shigeyuki
S
Wakitani
Masahiro
M
Tada
Hiroyasu
H
Morikawa
Masaru
M
Enomoto
Masaaki
M
Inaba
Tatsuya
T
Nakatani
Masayuki
M
Hino
Norifumi
N
Kawada
D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006509:Hepatitis B / Q000188:drug therapy / Q000821:virology*; D006512:Hepatitis B Core Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D017093:Liver Failure / Q000517:prevention & control / Q000821:virology; D008297:Male; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D017410:Practice Guidelines as Topic; D011446:Prospective Studies; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014775:Virus Activation / Q000187:drug effects*
D018501:Antirheumatic Agents; D000998:Antiviral Agents; D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; C413685:entecavir; D006147:Guanine
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