Changes in hepatitis B virus surface antibody titer and risk of hepatitis B reactivation in HBsAg-negative/HBcAb-positive patients undergoing biologic therapy for rheumatic diseases: a prospective cohort study

BackgroundOur aim was to investigate dynamic changes in hepatitis B virus (HBV) surface antibody (HBsAb) titer and the associated risk of HBV reactivation and clinical course in patients with HBV surface antigen negative/core antibody positive (HBsAg(-)/HBcAb(+)) serostatus during antirheumatic therapy with biologic agents.MethodsIn a prospective study from January 2013 to June 2017, we monitored the HBV serostatus of HBsAg(-)/HBcAb(+) patients undergoing biologic therapy for rheumatic diseases. From HBsAb titers at baseline and subsequent time points, we calculated the person-years (PY) contributed by patients with different HBsAb levels: <10 mIU/mL (negative); 10-100 mIU/mL (low); and>100 mIU/mL (high). We analyzed the incidence of detectable HBV DNA and HBV reactivation in each group, and documented the clinical courses of patients.ResultsAmong 380 participants, 83 (21.8%) had baseline HBsAb <10 mIU/mL, 156 (41.1%) HBsAb 10-100 mIU/mL, and 141 (37.1%) HBsAb >100 mIU/mL. Total PY at study end were 169.3 PY from the HBsAb-negative group, 362.7 PY from the low-titer group, and 285.8 PY from the high-titer group. Seventeen patients had detectable HBV DNA, with respective incidence rates in negative, low- and high-titer groups of 4.7/100 PY, 2.5/100 PY, and 0/100 PY. Two HBsAb-negative patients subsequently developed HBV reactivation, an incidence of 1.2/100 PY.ConclusionsThe risk of HBV reactivation varied with HBsAb titer, which changed during biologic therapy. Neither HBV DNA nor reactivation were detected in patients with HBsAb >100 mIU/mL, whereas HBV DNA without reactivation occurred periodically in patients with HBsAb 10-100 mIU/mL; HBsAb-negative serostatus was associated with a risk of HBV reactivation.