This retrospective multicenter questionnaire survey conducted in the North-east area of Japan demonstrated that approximately 1% patients with RA were current HBV carriers and more than 25% were considered to be resolved carriers. Previous reports in Japan showed similar results estimating that 25% (60/239) patients in Kumamoto and 31.5% (135/428) in Aomori were infected with HBV (Urata et al. 2011; Mori 2011), indicating that more than one-fourth patients with RA may be infected with HBV in Japan. However, the number of patients enrolled in this study is much larger than previous reports. To our knowledge, this is the largest study regarding prevalence of HBV infection in RA patients in Japan. Our data suggest that HBV screening and appropriate management of HBV should be strictly performed when initiating immunosuppressive therapy. Prevalence of HBV infection was significantly lower (16.5%; 41/248) in patients with SLE than that in patients with RA (Watanabe et al. 2013). It has been reported that older adults had a higher frequency of HBV infection that younger adults in Japan (Tanaka et al. 2011). Therefore, one reason to explain this may be the different ages of onset of RA and SLE. However, because high-dose corticosteroids and intensive immunosuppressive therapy, such as cyclophosphamide, are often required to treat patients with SLE, we should not overlook the risk of HBV reactivation, even in patients with SLE.
This retrospective survey is the first report about the rate of HBV screening before immunosuppressive therapy in Japan and also showed that the rate was low in routine clinical practice. However, previous reports from oncologists showed similar results (Tran et al. 2010; Day et al. 2011a, b; Hwang et al. 2012; Zurawska et al. 2012; Lee et al. 2012). For example, Hwang et al. (2012) reported that among 10,729 patients who received chemotherapy, only 1,787 (16.7%) underwent screening for HBsAg or HBcAb. As for rheumatologists, Stine et al. (2010) conducted a nationwide questionnaire survey about HBV screening in 1,000 ACR members. Responses obtained (153/1,000, 15.3%) were highly variable and more than half of the members did not check HBsAb or HBcAb prior to initiating therapy. The authors concluded that it is necessary to improve education among rheumatologists regarding the risks of HBV reactivation in patients in whom immunosuppressive therapy needs to be started.
Recent advances in treatment have changed the therapeutic goal of patients with RA and other rheumatic diseases (Harigai et al. 2014). Biologics, high-dose MTX, and corticosteroids are being increasingly used to induce remission or low disease activity. 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). Recently, with an increasing interest in HBV reactivation in Japan, the rate of HBV screening may continue to increase. Nevertheless, a new framework to improve the assessment of the risk of HBV reactivation and fulminant HBV hepatitis by Japanese rheumatologists needs to be developed.
Although fulminant HBV hepatitis was observed in 1 patient who was current carrier, fulminant hepatitis due to HBV reactivation in resolved carriers was not reported in this retrospective study. However, this does not mean that fulminant HBV hepatitis does not occur in resolved carriers because the rate of HBV screening was low. Therefore, we are now conducting a multicenter prospective study to investigate the rate of HBV reactivation in patients with rheumatic diseases under immunosuppressive therapy.
In conclusion, this retrospective questionnaire study demonstrated that approximately 20% or more patients with rheumatic diseases were infected with HBV and the rate of HBV screening before immunosuppressive therapy among rheumatologists was low in routine clinical practice. Although the incidence of fulminant HBV hepatitis was low, we rheumatologists should improve our consciousness regarding the risk of HBV reactivation and management of HBV infection.