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.

摘要

OBJECTIVE: To 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 (TNFalpha) inhibitors. METHODS: The authors investigated the virological, serological and biochemical evidence of HBV reactivation in 88 RA patients receiving anti-TNFalpha 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. RESULTS: In 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-TNFalpha therapy. Among HBsAg-positive patients receiving anti-TNFalpha 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-TNFalpha 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-TNFalpha therapy. CONCLUSION: HBV reactivation can occur in both HBsAg-positive and HBsAg-negative/HBcAb-positive patients with detectable HBV DNA, so-called occult HBV infection, during anti-TNFalpha therapy. Antiviral prophylaxis may effectively reduce HBV reactivation in HBsAg-positive RA patients undergoing anti-TNFalpha therapy.