Safety of tumor necrosis factor alpha blockers in hepatitis B virus occult carriers (hepatitis B surface antigen negative/anti-hepatitis B core antigen positive) with rheumatic diseases

Arthritis Care Res (Hoboken). 2010 Jun;62(6):749-54. doi: 10.1002/acr.20130.


Objective: To assess the safety of anti-tumor necrosis factor alpha (anti-TNFalpha) therapy on the course of hepatitis B virus (HBV) infection in carriers of antibodies to hepatitis B core antigen (anti-HBc) affected by chronic inflammatory arthropathies.

Methods: From January 2001 to December 2008, HBV markers were determined before the first administration of anti-TNFalpha agents in all 732 patients affected by inflammatory arthropathies treated with anti-TNFalpha at 2 outpatient rheumatologic clinics in Northern Italy. Anti-HBc-positive patients were prospectively evaluated and HBV markers and HBV DNA were assessed every 6 months, in case of aminotransferase elevation, and at the end of the study.

Results: At the time of recruitment, 72 patients were anti-HBc carriers, 5 of whom were positive for hepatitis B surface antigen (HBsAg) and not included in the study. The ratio of men:women was 26:41 and the mean +/- SD followup was 42.52 +/- 21.33 months. Of the patients, 25 were treated with infliximab, 23 with etanercept, and 19 with adalimumab. Fifty-one patients were treated also with methotrexate, 52 with nonsteroidal antiinflammatory drugs, and 43 with prednisone (3 with a dosage >7.5 mg/day). All anti-HBc patients were HBV DNA negative at the first observation. During followup, no patient presented HBV reactivation with viral load increase and no patient became HBsAg positive.

Conclusion: Anti-HBc positivity in HBsAg-negative patients is a sign of previous HBV infection and does not indicate chronic hepatitis. In these patients, anti-TNFalpha therapy appears to be quite safe, as no HBV reactivation was found in our study. Nevertheless, careful monitoring is necessary.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / adverse effects*
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Carrier State / blood*
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Hepatitis B Surface Antigens / biosynthesis*
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B virus / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Rheumatic Diseases / blood*
  • Rheumatic Diseases / drug therapy
  • Rheumatic Diseases / virology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / blood


  • Antiviral Agents
  • Hepatitis B Surface Antigens
  • Tumor Necrosis Factor-alpha