Liao Ya-Ping, Jiang Jia-Lu, Zou Wai-Yi, Xu Duo-Rong, Li Juan
Ya-Ping Liao, Jia-Lu Jiang, Wai-Yi Zou, Duo-Rong Xu, Juan Li, Department of Hematology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510000, Guangdong Province, China.
World J Gastroenterol. 2015 Apr 14;21(14):4284-92. doi: 10.3748/wjg.v21.i14.4284.
To investigate the timing, safety and efficacy of prophylactic antiviral therapy in patients with hepatitis B virus (HBV) infection undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).
This prospective study recruited a total of 57 patients diagnosed with malignant hematological diseases and HBV infection at the First Affiliated Hospital of Sun Yat-sen University between 2006 and 2013. The patients were classified as hepatitis B surface antigen (HBsAg)-positive or HBsAg-negative/ antiHBc-positive. Patients were treated with chemotherapy followed by antiviral therapy with nucleoside analogues. Patients underwent allo-HSCT when serum HBV DNA was < 10(3) IU/mL. Following allo-HSCT, antiviral therapy was continued for 1 year after the discontinuation of immunosuppressive therapy. A total of 105 patients who underwent allo-HSCT and had no HBV infection were recruited as controls. The three groups were compared for incidence of graft-vs-host disease (GVHD), drug-induced liver injury, hepatic veno-occlusive disease, death and survival time.
A total of 29 of the 41 subjects with chronic GVHD exhibited extensive involvement and 12 exhibited focal involvement. Ten of the 13 subjects with chronic GVHD in the HBsAg(-)/hepatitis B core antibody(+) group exhibited extensive involvement and 3 exhibited focal involvement. Five of the 10 subjects with chronic GVHD in the HBsAg(+) group exhibited extensive involvement and 5 exhibited focal involvement. The non HBV-infected group did not differ significantly from the HBsAg-negative/antiHBc-positive and the HBsAg-positive groups which were treated with nucleoside analogues in the incidence of graft-vs-host disease (acute GVHD; 37.1%, 46.9% and 40%, respectively; P = 0.614; chronic GVHD; 39%, 40.6% and 40%, respectively; P = 0.98), drug-induced liver injury (25.7%, 18.7% and 28%, respectively; P = 0.7), death (37.1%, 40.6% and 52%, respectively; P = 0.4) and survival times (P = 0.516). One patient developed HBV reactivation (HBsAg-positivity) due to early discontinuation of antiviral therapy.
Suppression of HBV DNA to < 10(3) IU/mL before transplantation, continued antiviral therapy and close monitoring of immune markers and HBV DNA after transplantation may assure the safety of allo-HSCT.
探讨乙型肝炎病毒（HBV）感染患者接受异基因造血干细胞移植（allo-HSCT）时预防性抗病毒治疗的时机、安全性和疗效。
这项前瞻性研究共纳入了2006年至2013年间在中山大学附属第一医院诊断为恶性血液病并伴有HBV感染的57例患者。这些患者被分为乙型肝炎表面抗原（HBsAg）阳性或HBsAg阴性/抗-HBc阳性。患者先接受化疗，随后用核苷类似物进行抗病毒治疗。当血清HBV DNA < 10³ IU/mL时，患者接受allo-HSCT。allo-HSCT后，在停用免疫抑制治疗后继续抗病毒治疗1年。共纳入105例接受allo-HSCT且无HBV感染的患者作为对照。比较三组患者的移植物抗宿主病（GVHD）、药物性肝损伤、肝静脉闭塞病、死亡发生率及生存时间。
41例慢性GVHD患者中，29例表现为广泛受累，12例表现为局灶性受累。HBsAg（-）/乙型肝炎核心抗体（+）组13例慢性GVHD患者中，10例表现为广泛受累，3例表现为局灶性受累。HBsAg（+）组10例慢性GVHD患者中，5例表现为广泛受累，5例表现为局灶性受累。未感染HBV组与接受核苷类似物治疗的HBsAg阴性/抗-HBc阳性组和HBsAg阳性组在移植物抗宿主病（急性GVHD发生率分别为37.1%、46.9%和40%；P = 0.614；慢性GVHD发生率分别为39%、40.6%和40%；P = 0.98）、药物性肝损伤（发生率分别为25.7%、18.7%和28%；P = 0.7）、死亡（发生率分别为37.1%、40.6%和52%；P = 0.4）及生存时间（P = 0.516）方面差异均无统计学意义。1例患者因过早停用抗病毒治疗发生HBV再激活（HBsAg阳性）。
移植前将HBV DNA抑制至< 10³ IU/mL，移植后持续抗病毒治疗并密切监测免疫指标和HBV DNA，可确保allo-HSCT的安全性。
