Use of tumor necrosis factor-alpha inhibitors in patients with chronic hepatitis B infection

Semin Arthritis Rheum. 2008 Dec;38(3):208-17. doi: 10.1016/j.semarthrit.2007.10.011. Epub 2008 Jan 25.


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.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Aged
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antiviral Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / virology
  • DNA, Viral / blood
  • Drug Therapy, Combination
  • Etanercept
  • Hepatitis B virus / drug effects
  • Hepatitis B virus / genetics
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Immunoglobulin G / adverse effects
  • Immunoglobulin G / metabolism
  • Immunoglobulin G / therapeutic use*
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / metabolism
  • Immunosuppressive Agents / therapeutic use*
  • Infliximab
  • Lamivudine / therapeutic use
  • Male
  • Receptors, Tumor Necrosis Factor / metabolism
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antibodies, Monoclonal
  • Antiviral Agents
  • DNA, Viral
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Lamivudine
  • Infliximab
  • Etanercept