Delayed Hepatitis B Active Viral Replications without Active Viral Biochemical Hepatitis Two Months after Cessation of Pre-Emptive Adefovir Therapy in a Patient with Waldenstrom Macroglobulinemia Treated with Rituximab and Fludarabine Chemotherapy.

Introduction:

Reactivation of HBV is a well-known complication in patients receiving cytotoxic therapy for malignancy. The incidence of hepatitis directly resulting from reactivation of HBV has been reported as 49% in HBs antigen-positive-patients with lymphoma. Preemptive use of lamivudine has successfully reduced the fatal complication of HBV reactivation after chemotherapy. The Optimal duration of Lamivudine adminstration has not yet been defined, although additional 1–2 months of therapy after chemotherapy cessation is recommended according to some studies.

The efficacy and duration of therapy with Adefovir has not been established in the same circumstances.

Method:

A 32-year-old Fillipino female, who presented in September 2004 with Waldenstrom Macroglobulinemia. She was found to have Hepatitis B surface antigen positive. Other Hepatitis B related laboratory testing revealed negative hepatitis B Delta antibody, negative hepatitis BE antigen negative hepatitis B core antibody IgM and positive hepatitis BE antibody.

Hepatitis B DNA less than 500 copies/ML. Patient was started on pre-emptive Adefovir during her treatment with 4 cycles of Fludrabine followed by four weekly treatment with rituximab. She achieved partial response and Adefovir was discontinued two months after completion of chemotherapy and Rituximab. Prior to proceeding with high dose chemotherapy with stem cell support four months after discontinuation of Adefovir, repeat hepatitis B DNA revealed more than 10 millon copies with normal biochemical profile.

Conclusion:

Use of adefovir for during and for 2 months after Rituximab containing chemotherapy was not successful in preventing reactivation of hepatitis B virus, and extreme caution should be practiced when treating a patient with a positive HBs antigen with Rituximab containing chemotherapy. Also the optimal duration for continuing HBV prophylaxis is not known, but clearly 2 months is a suboptimal duration. It is unknown if adefovir is as effective as lamivudine in preventing reactivation of HBV with Rituximab. The lag of HBV related hepatitis despite active viral replication cholud be related to prior immune-suppression by Rituximab and Fludarabine.