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

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.