Background/Purpose: Reactivation of resolved hepatitis B in patients undergoing immunosuppressive therapy is now considered to be a complication of major clinical importance. Because this is still an emerging concept, the majority of our patients with autoimmune disease have been tested only for hepatitis B surface antigen (HBsAg), and not for hepatitis B surface antibody (anti-HBs) or hepatitis B core antibody (anti-HBc) in our country. We evaluated the prevalence of previous infection of hepatitis B virus (HBV) in patients with autoimmune disease and the incidence of its reactivation.

Methods: We enrolled 318 patients (63 males, 255 females) with autoimmune disease, who were receiving, or were scheduled to receive, immunosuppressants at our hospital. The immunosuppressants included methotrexate (MTX), tacrolimus (TAC), mizoribine (MZR), prednisolone (PSL) at over 30 mg/day, azathioprine (AZ), cyclosporine (CyA), cyclophosphamide (CPA), etanercept (ETN), infliximab (IFX), tocilizumab (TCZ), adalimumab (ADA), and abatacept (ABA). Patients underwent HBV serological examination including HBsAg, anti-HBs, and anti-HBc. When HBsAg, anti-HBs and/or anti-HBc were positive, HBV-DNA was measured once a month using a real-time polymerase chain reaction assay. Clinical data were examined by reviewing the medical records.

Results: Among the 318 patients, 4 were HBsAg positive and the rest were HBsAg negative; 61 patients were anti-HBs positive and 70 were anti-HBc positive. Eighty patients (rheumatoid arthritis (RA) 72, systemic lupus erythematosus (SLE) 4, adult-onset Still’s disease 1, polymyositis 1, polymyalgia rheumatica 1, juvenile rheumatoid arthritis 1) showed HBsAg negative and anti-HBs and/or anti-HBc positive serology, indicating previous HBV infection. Among these patients, 72 had already been treated with immunosuppressive agents as monotherapy or in combination (MTX 42, TAC 25, MZR 11, high-dose PSL 5, AZ 3, CyA 1, CPA 1, ETN 9, IFX 7, TCZ 4, ADA 1, ABA 1) for 43.9 ± 44.4 months (range 4-248 months, median 32 months) before evaluation of anti-HBs and anti-HBc without developing acute hepatitis. Another 8 patients were scheduled to begin immunosuppressive therapy. Among patients with past HBV infection, 5 were positive for viral replication (>2.1 log copies/ml). The first of these patients had SLE, and the other four had RA. Among them, a patient was treated with high-dose PSL and CPA. She was HBsAg negative at the start of immunosuppressant therapy, but 3 months later HBV-PCR increased to 7.9 log copies/ml, and HBsAg became weakly positive with elevation of the transaminase level. The second patient was treated with 3 mg/day TAC, 150 mg/day MZR and 5 mg/day PSL, and the third with 3 mg/day TAC and 5 mg/day PSL. Two patients who were treated only with sulfasalazine and bucillamine, showed reactivation of HBV in the absence of immunosuppressants.

Conclusion: Reactivation of HBV sometimes occurs without MTX or biological agents. Patients in whom hepatitis B infection has serologically been resolved, need to be monitored carefully even when receiving immunosuppressants other than MTX, or biological agents.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/reactivation-of-hepatitis-b-virus-in-autoimmune-disease-patients-receiving-immunosuppressive-agents/