Hepatitis B Virus Reactivation and Alemtuzumab Therapy.

Reactivation of hepatitis B virus infection in subjects receiving cytotoxic treatment for haematological malignancies occurs in 21–53% of chronic HBsAg carriers and in an unknown number of HBsAg negative subjects harbouring occult HBV infection. Immunotherapy with alemtuzumab, a humanized monoclonal antibody against CD52 on lymphoid cells, produces deep immunosuppression. We describe two subjects with chronic lymphocytic leukaemia and occult HBV infection who developed a virological and biochemical flare of hepatitis B following immunotherapy with alemtuzumab. One of them developed a full blown hepatitis with seroreversion from anti-HBs to HBsAg after four weeks of alemtuzumab. Lamivudine (100 mg die) achieved a complete clinical recovery and HBV-DNA clearance from blood within 8 weeks. The second patient (HBsAg and HBV-DNA seronegative, anti-HBs and anti-HBc positive before treatment) was kept under prophylaxis with lamivudine up to three months after alemtuzumab. Two months after withdrawal of lamivudine, clinical and laboratory features of acute hepatitis B developed. Lamivudine therapy was restarted and obtained a prompt recovery with HBsAg and HBV-DNA clearance.

These cases suggest that alemtuzumab, as all other immune response modifiers, should be used cautiously when HBV infection is present. While a recommendation for universal pre-emptive treatment with lamivudine of all HBsAg positive patients undergoing effective immunosuppressive treatment can be made it is more difficult to establish a pattern for patients who have serological markers of previous HBV infection (anti-HBs and/or anti-HBc) and even more for those with no HBV markers. Testing for HBV-DNA in serum by highly sensitive PCR may discover up to 50% of these cases, allowing preemptive lamivudine therapy. A substantial proportion would however go undiscovered in the absence of a liver biopsy, which is clearly an unfeasible proposition as a screening procedure. Once a reactivation has been documented, nucleoside analog therapy should last for a few months after HBV-DNA clearance.