Possible Reactivation of Potential Hepatitis B Virus Occult Infection by Tumor Necrosis Factor-α Blocker in the Treatment of Rheumatic Diseases

• Published in: Journal of rheumatology 2010-02, Vol.37 (2), p.346-350
• Main Authors: YUN JUNG KIM, BAE, Sang-Cheol, SUNG, Yoon-Kyoung, KIM, Tae-Hwan, JUN, Jae-Bum, YOO, Dae-Hyun, TAE YEOB KIM, JOO HYUN SOHN, LEE, Hye-Soon
• Format: Article
• Language: English
• Subjects: Adalimumab; Adult; Aged; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Biological and medical sciences; Disease Susceptibility - immunology; Diseases of the osteoarticular system; Etanercept; Female; Hepatitis B - immunology; Hepatitis B virus - immunology; Human viral diseases; Humans; Immunoglobulin G - therapeutic use; Infectious diseases; Infliximab; Male; Medical sciences; Middle Aged; Miscellaneous. Osteoarticular involvement in other diseases; Receptors, Tumor Necrosis Factor - antagonists & inhibitors; Receptors, Tumor Necrosis Factor - immunology; Receptors, Tumor Necrosis Factor - therapeutic use; Regression Analysis; Retrospective Studies; Rheumatic Diseases - immunology; Rheumatic Diseases - therapy; Viral diseases; Viral hepatitis
• ISSN: 0315-162X; 1499-2752
• DOI: 10.3899/jrheum.090436

To assess the safety of anti-tumor necrosis factor (TNF-alpha) therapy in patients with rheumatic diseases in terms of the reactivation of potential hepatitis B virus (HBV) occult infection. Patients who had taken anti-TNF-alpha for the treatment of rheumatic diseases from January 2002 to May 2008 were included in the study. In this patient group, we retrospectively investigated a series of serum aminotransferase levels, HBV serologic status, the type of anti-TNF-alpha therapy, duration of the anti-TNF-alpha treatment, and concurrent use of hepatotoxic drugs. A total of 266 cases were documented using 3 serologic markers for HBV infection: HBV surface antigen (HBsAg), HBV surface antibody (HBsAb), and HBV core IgG Ab (HBcAb). Of these, 8 cases had chronic hepatitis B (HBsAg+), 170 cases were HBcAb-negative, and 88 cases were identified as having potential HBV occult infections represented by HBsAg-negative and HBcAb-positive, irrespective of the status of the HBsAb. The frequency of clinically significant (> 2 times normal value) and persistent increase (> 2 consecutive tests) of aminotransferase levels was significantly higher in the group with a potential HBV occult infection compared to the HBcAb-negative group. In the multiple logistic regression analysis controlling for various potential confounding factors such as prophylactic anti-tuberculosis medication, methotrexate, nonsteroidal antiinflammatory drugs, and the type of anti-TNF-alpha therapy, only potential HBV occult infection was a significant risk factor for abnormal liver function test (LFT). All rheumatic patients who plan to take anti-TNF-alpha treatment should undergo a test for HBV serology, including HBcAb, and have a close followup with an LFT test during therapy. Further prospective studies for hepatitis B viral load using HBV-polymerase chain reaction in patients who are HbcAb positive are needed to identify whether the abnormal LFT comes from the reactivation of occult HBV infection.