Use of tumor necrosis factor-alpha inhibitors in patients with chronic hepatitis B infection.
OBJECTIVE
Tumor necrosis factor-alpha (TNF-alpha) inhibitors have emerged as a potent treatment for rheumatoid arthritis (RA), but not without significant risks. In chronic hepatitis B viral infection TNF-alpha is readily produced, and viral clearance is dependent on the amount bioavailable. Limited data suggest that TNF-alpha inhibitors may facilitate uncontrolled hepatitis B viral replication. The purpose of this article was to provide a detailed review of the role of TNF-alpha in controlling hepatitis B viral infection and the clinical impact blockade might have on viral control.


METHODS
We describe a patient with chronic hepatitis B viral infection and RA treated with etanercept. We then review case reports, expert opinion, and manufacturer recommendations regarding hepatitis B viral infection, TNF-alpha, and TNF-alpha inhibitors.


RESULTS
To date, 13 patients with chronic hepatitis B infection treated with TNF-alpha inhibitors have been reported: 11 with infliximab and 2 with etanercept. Some patients received antiviral therapy for hepatitis B (specifically lamivudine) before, during, or after TNF-alpha inhibitors were started. Clinically apparent reactivation of hepatitis B virus typically occurred 1 month after the 3rd dose of infliximab. Etanercept was not associated with a similar reactivation. The difference between infliximab and etanercept in viral reactivation may be linked to the pharmacologic difference of each medication.


CONCLUSIONS
TNF-alpha inhibitors in general should be used cautiously in chronic hepatitis B viral infection. But if necessary, when deciding which agent to use, the clinician should consider the mechanism by which the body clears TNF-alpha.
Carroll
Matthew B
MB
San Antonio Uniformed Services Health Education Consortium (SAUSHEC), Wilford Hall Medical Center, Lackland Air Force Base, Lackland, Texas, USA. matthew.carroll@keesler.af.mil
Bond
Michael I
MI
D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000821:virology; D004279:DNA, Viral / Q000097:blood; D004359:Drug Therapy, Combination; D000068800:Etanercept; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D000069285:Infliximab; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D004279:DNA, Viral; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D019259:Lamivudine; D000069285:Infliximab; D000068800:Etanercept