Kinetics of viral loads and risk of hepatitis B virus reactivation in hepatitis B core antibody-positive rheumatoid arthritis patients undergoing anti-tumour necrosis factor alpha therapy

Abstract

ObjectiveTo investigate the kinetics of hepatitis B virus (HBV) viral loads and HBV reactivation in rheumatoid arthritis (RA) patients undergoing therapy with tumour necrosis factor alpha (TNFα) inhibitors.MethodsThe authors investigated the virological, serological and biochemical evidence of HBV reactivation in 88 RA patients receiving anti-TNFα therapy. Levels of HBV surface (HBs) antigen (Ag), anti-HBV core (HBc)-IgG and anti-HBs antibody (Ab) were detected by electrochemiluminescence immunoassay, and viral loads were determined by real-time PCR assay.ResultsIn a total of 88 HBcAb-positive patients, 18 (20.5%) patients were HBsAg-positive, 12 (13.6%) patients were HBsAg-negative/HBsAb-negative and 58 (65.9%) patients were HBsAg-negative/HBsAb-positive before starting anti-TNFα therapy. Among HBsAg-positive patients receiving anti-TNFα therapy, HBV reactivation was documented in none of 10 patients who received lamivudine pre-emptive therapy and serum viral loads significantly decreased (mean±SEM, 153 860±80 120 IU/ml at baseline vs 313±235 IU/ml after 12 months antiviral therapy, p<0.001), paralleling the decrease in serum aminotransferase levels. In contrast, five (62.5%) of eight patients without antiviral prophylaxis developed HBV reactivation, viral loads significantly increased after anti-TNFα therapy (9375±5924 IU/ml vs 49 710 000±40 535 000 IU/ml, p<0.001), and markedly declined after antiviral therapy (49 710 000±40 535 000 IU/ml vs 6382±2424 IU/ml, p<0.001). Baseline viral loads were detectable in four (33.3%) of 12 patients who had HBsAg-negative/HBsAb-negative status, and one developed HBV reactivation after anti-TNFα therapy.ConclusionHBV reactivation can occur in both HBsAg-positive and HBsAg-negative/HBcAb-positive patients with detectable HBV DNA, so-called occult HBV infection, during anti-TNFα therapy. Antiviral prophylaxis may effectively reduce HBV reactivation in HBsAg-positive RA patients undergoing anti-TNFα therapy.