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[PubMed] [Google Scholar] 6. rheumatic disease, three of whom were receiving a pharmacological dose of corticosteroids only, and three who were receiving corticosteroids with immunosuppressants and/or DMARDs. However, no reactivation occurred in patients receiving corticosteroid replacements for adrenal insufficiency. Maintenance and maximum corticosteroid doses administered to patients with rheumatic disease were significantly greater than those in patients with adrenal insufficiency. Conclusion These results suggest that, although corticosteroid replacement therapy for adrenal insufficiency might be safe with respect to HBV reactivation, attention should be paid to HBV reactivation during corticosteroid therapy in rheumatic disease patients, since the dose of corticosteroids administered is usually large, and since other Deferitrin (GT-56-252) immunosuppressants are co\administered. strong class=”kwd-title” Keywords: adrenal insufficiency, corticosteroids, hepatitis B virus reactivation, rheumatic disease 1.?INTRODUCTION Hepatitis B virus (HBV) reactivation occurring in patients undergoing cytotoxic chemotherapy and/or immunosuppressive therapy is a well\recognized complication of considerable clinical importance. Reactivation of HBV is usually more often seen in hepatitis B carriers who are positive for hepatitis B surface (HBs) antigen (Ag) and for antibody (Ab) against hepatitis B core (HBc). Acute hepatitis, that is, de novo hepatitis, is likely to occur because of HBV reactivation during chemotherapy and/or immunosuppressive therapy given to patients with transplanted organs and leads to variable manifestations that range from subclinical serum aminotransferase elevation to fatal fulminant hepatitis. However, a few cases of HBV reactivation in patients with resolved contamination as defined by unfavorable HBsAg and positive HBcAb with or without HBsAb have been reported during chemotherapy or immunosuppressive therapy.1, 2 The incidence of de novo hepatitis due to HBV reactivation in HBsAg\negative patients with malignant lymphoma treated with corticosteroid\containing cytotoxic chemotherapy Deferitrin (GT-56-252) was reported to be 2.7% over a 4\year period and 3.3% during a 12.4\month follow\up.3, 4 Vegfa However, use of rituximab, an anti\CD20\directed monoclonal antibody, in combination with corticosteroid\containing chemotherapy, has been frequently associated with HBV reactivation and resultant de novo hepatitis.4, 5, 6 Most of these reports come from the fields of oncology and transplantation, with a growing number of cases being reported in patients with rheumatic disease who are also undergoing immunosuppressive therapy. The incidence of HBV reactivation was reported to be 7/135 (5.2%) after a 1\year prospective observation in rheumatoid arthritis patients with resolved hepatitis B treated with corticosteroids, immunosuppressants and/or disease\modifying antirheumatic drugs (DMARDs).7 A recent prospective observational study in Japan has reported that HBV reactivation among rheumatic disease patients with resolved HBV infections treated with prednisone, immunosuppressants and/or biological DMARDs, occurred in 35/1042 (3.4%) of individuals over a period of 2?years.8 Estimated incidence rates of HBS reactivation and hence de novo hepatitis vary, likely due to differences among the patient populations studied, drugs administered and the duration of follow\up. Of all the traditional immunosuppressive medications, corticosteroids have been most often implicated in the induction of HBV reactivation. The risk of HBV reactivation in patients with inflammatory bowel disease, vasculitis, sarcoidosis and autoimmune disease might differ, depending on whether the patients are HBsAg\positive/HBcAb\positive or HBsAg\unfavorable/HBcAb\positive, whether the dosage of chronic prednisone therapy is usually low, moderate or high, or whether the duration is usually short or longer than 4?weeks.8, 9 However, the exact incidence rate of HBV reactivation in HBsAg\negative/HBcAb\positive patients with autoimmune disease Deferitrin (GT-56-252) such as rheumatoid arthritis treated only with corticosteroids has not been fully evaluated. On the other hand, adrenal insufficiency is usually treated with optimal alternative dose corticosteroids, equivalent to 5?mg of prednisone/day, to achieve physiological plasma cortisol levels comparable to those in healthy individuals. The incidence of HBV reactivation in patients with adrenal insufficiency given.