Prevalence of reactivation of hepatitis B virus replication in rheumatoid arthritis patients

Department of Rheumatology, Seihoku Chuo Hospital, 41 Nunoyacho, Gosyogawara, 037-0053, Japan.
Modern Rheumatology (Impact Factor: 2.4). 02/2011; 21(1):16-23. DOI: 10.1007/s10165-010-0337-z
Source: PubMed


Reactivation of hepatitis B involves the reappearance of active necroinflammatory liver disease after an inactive hepatitis B surface antigen (HBsAg) carrier state or resolved hepatitis B, occurring during or after immunosuppression therapy or chemotherapy. We prospectively investigated the reactivation rate for hepatitis B virus (HBV) DNA replication in cases of rheumatoid arthritis (RA) with resolved hepatitis B. HBV markers were evaluated in 428 RA patients. Patients with positive findings of HBsAg or HBV DNA at enrolment were excluded. The study population comprised 422 RA patients, with resolved hepatitis B diagnosed in 135 patients based on HBsAg-negative and antihepatitis B core antibody/antihepatitis B surface antibody-positive results. HBV DNA was measured every 3 months in this group, and if HBV DNA became positive after enrolment, measurement was repeated every month. HBV DNA became positive (≥3.64 log copies/mL) in 7 of 135 patients for 12 months. Use of biologic agents was significantly more frequent in patients who developed reactivation of HBV DNA replication (85.7%) than in patients who did not (36.0%, p = 0.008). Hazard ratios for use of biologic agents and etanercept were 10.9 (p = 0.008) and 6.9 (p = 0.001), respectively. RA patients with resolved hepatitis B need careful monitoring when receiving biologic agents, regardless of HBV DNA levels.

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Available from: Yoshihide Nakamura, Jan 02, 2014
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    • "Among them, the use of biologics , such as tumor necrosis factor-α inhibitors, may cause HBV reactivation (Urata et al. 2011). However, MTX and corticosteroids also have the potential to induce HBV reactivation and de novo hepatitis (Urata et al. 2011; Harigai et al. 2014). The use of biologics is now contraindicated in current HBV carriers (Harigai et al. 2014); however , some rheumatologists prescribe them for current HBV carriers in this study (Table 1). "
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    ABSTRACT: Hepatitis B virus (HBV) reactivation has been increasingly recognized in patients receiving chemotherapy and immunosuppressive therapy; however, the prevalence of HBV infection and rate of HBV screening in patients with rheumatic diseases remains unclear. In this study, we aimed to assess the prevalence of HBV infection and fulminant HBV hepatitis in patients with rheumatic diseases. We also investigated the rate of HBV screening before immunosuppressive therapy in patients with rheumatic diseases. A retrospective questionnaire survey was conducted in the North-east area (Tohoku) of Japan. Questionnaires, comprising 6 questions, were sent to 318 rheumatologists in May 2010, and responses were gathered until June 2011. In total, 71 rheumatologists (22.3%) responded to the survey. We enrolled 7,650 patients with rheumatoid arthritis (RA) and 1,031 patients with systemic lupus erythematosus (SLE). When limited to institutes at which almost all (≥ 90%) patients were tested for HBV serology, 1.1% (40/3,580) patients with RA and 0.3% (3/1,128) patients with SLE were positive for hepatitis B surface antigen (HBsAg), and 25.2% (177/703) patients with RA and 13.7% (34/248) patients with SLE were positive for hepatitis B core antibody (HBcAb). About one-third of rheumatologists did not check HBsAg and more than half did not check hepatitis B surface antibody (HBsAb) or HBcAb at all before therapy. Fulminant HBV hepatitis was observed in 1 RA patient who was current HBV carrier. In conclusion, the prevalence of HBV infection is high in patients with RA and SLE. HBV screening before immunosuppressive therapy should be strictly performed.
    Full-text · Article · Jun 2014 · The Tohoku Journal of Experimental Medicine
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    • "In contrast to the above findings, several cases of HBV reactivation with viremia and emergence of HBsAg have been reported in patients with past HBV infection during immunosuppressive therapy for Crohn’s disease, ankylosing spondylitis, and RA [24–26]. Most recently, Urata et al. [21] have reported a high prevalence of HBV reactivation with marked increases in viral load in Japanese patients with RA and resolved HBV infection. In their study, 7 out of 135 patients (5.2%) in the resolved infection group became positive for HBV DNA (equal to or higher than 3.64 log copies/ml) at some point during a 12-month period of therapy. "
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    ABSTRACT: To evaluate the prevalence of past infection with hepatitis B virus (HBV) in patients with rheumatoid arthritis (RA) and the incidence of its reactivation under treatment with biological and/or nonbiological disease-modifying antirheumatic drugs (DMARDs), 239 patients receiving DMARD therapy were consecutively enrolled and tested for HBV-DNA, using a real-time polymerase chain reaction assay, HBV serology including hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc), and serum levels of aminotransferase. Data prior to DMARD therapy and during follow-up were examined by reviewing medical records. Two patients (0.8%) were positive for HBsAg at the start of therapy. Sixty patients (25.1%) showed HBsAg-negative and anti-HBc-positive serology indicative of past HBV infection. Among these 60 patients, 2 patients (3.3%) experienced reactivation of viral replication (<2.1 log copies/ml) during DMARD therapy. One had been receiving tacrolimus, prednisolone, and methotrexate (MTX); the other had been treated with adalimumab, prednisolone, and MTX. Their serum aminotransferase levels remained normal, and HBsAg was negative. Ten weeks after reactivation of viral replication had been noted, the HBV-DNA titer in the former patient had increased to 2.9 log copies/ml, and HBsAg and hepatitis B e antigen had become weakly positive. In contrast, the latter patient had become negative for viral DNA without any antiviral prophylaxis. In conclusion, the use of biological and nonbiological DMARDs is relatively safe in most RA patients with past HBV infection, even when no anti-HBV prophylaxis is administered. Considering the high prevalence of past infection in RA patients and the high cost of prophylaxis against HBV reactivation, universal prophylaxis is impractical. Regular monitoring of serum viral DNA seems to be the most rational approach to preventing the development of clinically apparent hepatitis.
    Preview · Article · Apr 2011 · Modern Rheumatology
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