Nucleos(T) Ides As Prophylaxis For Reactivation Of Hepatitis B In Immunosuppression

Objective: Hepatitis B virus (HBV) will become reactive in non-active HBsAg carriers when they are in the immunosuppression status, which is often caused by cytotoxic drugs in chemotherapy or immunosuppressants. Liver damage will be induced in such patients and even liver failure in some patients. The aim of this study was to investigate the incidence of HBV reactivation and its clinical characteristics in the non-active HBsAg carriers receiving chemotherapy or immunosuppressant treatment for tumors or other immune disorders, and evaluate the role of nucleos(t)ide analogues against HBV reactivation, which may provide evidence for prevention such diseases.Methods: Non-active HBsAg carriers suffering from cancer, autoimmune diseases and needing the treatment of immunosuppressants or cytotoxic chemotherapy were enrolled in the study. The in-patients from June 2002 to April 2007 in the Second Affiliated Hospital of Chongqing Medical University were assigned in control group. The characteristics of HBV replication, liver damage, clinical symptoms and effectiveness of nucleos(t)ide analogues as prophylaxis for HBV reactivation were observed. The outpatients or in-patients with the same disease condition as in retrospective group from April 2007 to July 2008 were enrolled in preventive group. The nucleos(t)ide analogues were used in cancer patients 1-2 weeks before chemotherapy, and the duration lasted 6-12 months according to patients'compliance after completion of chemotherapy. Patients with other diseases used nucleos(t)ide analogues in 1-3 months before using glucocorticoids or other immunosuppressive agents, and continued to use for 6-12 months after accomplishing the course of immunosuppressant treatment. The characheristics and clinical manifestations about HBV reactivation were investigated.Results: Of the thirty two patients in preventive group, twenty two patients suffered from cancer, eight patients suffered from idiopathic thrombocytopenic purpura, two patients suffered from chronic nephritis. The nucleos(t)ide analogues(lamivudine, entecavir, telbivudine, etc.) were used in antiviral therapy before chemotherapy or immunosuppressive treatment .The amount of HBV DNA and liver function were detected in the first, third, sixth and 12th month after use of nucleos(t)ide analogues. After chemotherapy or immunosuppressant treatment, only 9.4% (3 / 32) of them suffered from HBV reactivation, which presented with HBV DNA positive and abnormal liver function. Of the 77 patients in control group, thirty seven patients suffered from cancer, thirteen patients suffered from chronic nephritis, twelve patients suffered from rheumatoid arthritis, fourteen patients suffered from idiopathic thrombocytopenic purpura, one patients suffered froms vasculitis. All the patients in this group did not use nucleos(t)ide analogues before chemotherapy or immunosuppressant, and the quantitative of HBV DNA was detected after abnormal liver function, in which 58.4% (45/77) of patients presented with HBV reactivation. There was big difference compared with that in the prospective group with respect to ratio of HBV reactivation by X2-test(P <0.005). HBV reactivation relative risk (RR) value <1 after nucleos(t)ide analogues of preventive therapy shows that the preventive application of nucleoside analogs was the protection factors, which made the risk of HBV reactivation reduction.The nucleos(t)ide analogues were used in antiviral therapy when the patients were found positive for HBV DNA in control group, but five patients still developed liver failure. Among them, four patients died and one patient undertook liver transplantation. Fourteen cases of 33 cancer patients (42.4%) suffered from HBV reactivation after chemotherapy. While 31 cases of 44 (70.5%) other patients who administered glucocorticoids or other immunosuppressant suffered from HBV reactivation, the HBV reactivation rate was significantly higher than the former.All the patients with HBV reactivation showed obvious jaundice and elevated transaminase.Conclusion: Non-active HBsAg carriers would appear potential incidence of HBV reactivation during use of chemotherapy or immunosuppressant, leading to impaired liver function and severe prognosis. Some cases may worsen with liver failure which may cause death. Nucleos(t)ide analogues should be used in early phase as prophylaxis for reactivation of hepatitis B in immunosuppression and to improve clinical prognosis.