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Arch Hellen Med, 28(2), March-April 2011, 151-165


Biological agents and hepatitis

S.P. Dourakis
Second Department of Medicine, "Hippokration" General Hospital, Medical School, Athens, Greece

Hepatitis B virus (HBV) reactivation is a serious but preventable clinical complication of immunosuppression, with substantial morbidity and mortality, caused by immune reconstitution of specific immunity to specific viral epitopes. Tumor necrosis factor-α (TNF-α) inhibition has emerged as a potent treatment for rheumatic and inflammatory bowel disease, but it is not without significant risks. TNF-α is readily produced in chronic ΗBV infection, and viral clearance is dependent on the amount available. TNF-α inhibition may facilitate uncontrolled HBV replication unless anti-viral prophylaxis is used for at least 6−12 months after the cessation of immunosuppression. The type of TNF-α used could make a difference. Infliximab, because of its effect on membrane-bound and soluble TNF-α, may be a more potent suppressor of the cellular immune response than etanercept and adalimumab. This suppression may lead to a disproportionate immune response on reconstitution. Patients with severe reactivation may have a fatal outcome despite treatment with either lamivudine or preferably newer more potent antivirals (entecavir or tenofovir). Some patients requiring a longer duration of lamivudine therapy are at risk of developing drug resistance. The newer agents entecavir or tenofovir should be used in such cases. Severe ΗΒV infection reactivation following profound and durable B and T cell depletion induced by treatment with rituximab or alemtuzumab has been reported in patients with either HΒsAg positive, or HBsAg negative and anti-HBc positive infection. In general, long-term prophylactic anti-HBV therapy is a more effective strategy than giving treatment after development of reactivation. A full HBV serologic profile must be obtained from all patients receiving intensive immunosuppressive or immunomodulatory therapy. Increasing use of the HBV vaccine may help to reduce the disease burden worldwide. Recent evidence confirms the efficacy and safety of anti-TNF-α agents in hepatitis C virus (HCV) associated rheumatic disorders. Rituximab is an effective treatment of severe and or refractory HCV-related vasculitis. Caution is recommended when prescribing biological therapies to patients with chronic hepatitis C. Patients should be closely monitored for changes in liver function tests or viral blood titers.

Key words: Alemtuzumab, Anti-TNF-α agents, Chronic hepatitis B, Chronic hepatitis C, Hepatitis B virus, Rituximab.

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