title: Possible reactivation of potential hepatitis B virus occult infection by tumor necrosis factor-alpha blocker in the treatment of rheumatic diseases.
abstract: 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 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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Hanyang University College of Medicine, Guri, Republic of Korea.
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Kim
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Bae
authors.forename: Yoon-Kyoung
authors.initials: YK
authors.lastname: Sung
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Kim
authors.forename: Jae-Bum
authors.initials: JB
authors.lastname: Jun
authors.forename: Dae-Hyun
authors.initials: DH
authors.lastname: Yoo
authors.forename: Tae Yeob
authors.initials: TY
authors.lastname: Kim
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Sohn
authors.forename: Hye-Soon
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D004198:Disease Susceptibility / Q000276:immunology; D000068800:Etanercept; D005260:Female; D006509:Hepatitis B / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000627:therapeutic use; D012044:Regression Analysis; D012189:Retrospective Studies; D012216:Rheumatic Diseases / Q000276:immunology / Q000628:therapy*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept