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

Objective. 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. Methods. 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 croup, 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. Results. 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). Conclusion. All rheumatic patients who plan to take anti-TNF-alpha treatment should undergo a test for serology, including HBcAb, and have a Close followup with an LFT test during. therapy. Further prospective studies for hepatitis B viral loud 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. (First Release Dec 15 2009: J Rheumatol 2010:37:346-50: doi: 10.3899/jrheum.090436)Supported by a grant of the Korea Healthcare Technology R&D Project, Ministry of Health, Welfare and Family Affairs, Republic of Korea (A084794)