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 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.
Kim
Yun Jung
YJ
Division of Rheumatology, Department of Internal Medicine, Hanyang University College of Medicine, Guri, Republic of Korea.
Bae
Sang-Cheol
SC
Sung
Yoon-Kyoung
YK
Kim
Tae-Hwan
TH
Jun
Jae-Bum
JB
Yoo
Dae-Hyun
DH
Kim
Tae Yeob
TY
Sohn
Joo Hyun
JH
Lee
Hye-Soon
HS
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*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept