关键词: 急性髓系白血病, 乙型肝炎病毒再激活, 预防性抗病毒治疗

Abstract: Background and purpose: Hepatitis B virus (HBV) reactivation is one of the serious complications among patients with acute myeloid leukemia (AML) following cytotoxic induction and consolidation chemotherapy. Nucleoside analogs including lamivudine and entecavir have been widely used as prophylactic or preemptive treatment for HBV reactivation. This study was to investigate clinical efficacy and safety of long or short course oral anti- HBV agents for preventing HBV reactivation in AML patients with HBV infection during chemotherapy. Methods: The medical records of 29 AML patients with HBV infection receiving at least 4 courses of chemotherapy were retrospectively identified and systematically analyzed. These patients were further divided into four groups according to their hepatitis B surface antigen (HBsAg) status prior to initiation of chemotherapy and duration of prophylactic therapy. Reactivation of HBV and toxicity profiles of oral antiviral agents were systematically analyzed and compared among different groups. Results: HBV reactivation and documented HBV-related hepatitis were significantly lower in AML patients under long course antiviral prophylaxis (i.e. continuing oral antiviral therapy for at least 6 months after cessation of chemotherapy, LCP group) than in the patients with short course antiviral prophylaxis (i.e. continuing oral antiviral therapy for one month after cessation of chemotherapy, SCP group), which was 5.56% (1/18) and 0% (0/18) compared with 45.45% (5/11) and 36.36% (4/11) (P=0.018 and P=0.014). There was little difference in the incidence of antiviral resistance between LCP and SCP groups ［11.11% (2/18) vs 9.09% (1/11), P>0.05］. Furthermore, the rates of HBV reactivation and HBV-related hepatitis were significantly lower in AML patients with positive HBsAg (HBsAg≥0.05 IU/mL) under long course antiviral prophylaxis than in HBsAg positive patients who received short course antiviral agents ［8.33% (1/12) and 0% (0/12) vs 66.67% (4/6) and 66.67% (4/6), P=0.022 and P=0.005］. Meanwhile, there was little difference in the rates of antiviral resistance between LCP and SCP groups among HBsAg positive patients ［8.33% (1/12) vs 16.67% (1/6), P>0.05］. In addition, the rates of HBV reactivation and HBV-related hepatitis as well as antiviral resistance were shown to have little difference in AML patients with negative HBsAg (HBsAg<0.05 IU/mL) between LCP and SCP groups. Concerning antiviral agent toxicity, no grade 3-4 toxicity occurred in patients from LCP or SCP group. Conclusion: Long course prophylaxis with oral antiviral agent appears to be an effective and well tolerated preventative approach for reducing risks of HBV reactivation and associated events in AML patients with positive HBsAg during chemotherapy, which serves as a platform for the design of prospective clinical trials.

Key words: Acute myeloid leukemia, Hepatitis B virus reactivation, Prophylactic antiviral therapy