Sperl J, Frankova S, Kieslichova E, Oliverius M, Janousek L, Honsova E, Trunecka P, Spicak J
Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Transplant Proc. 2013 Sep;45(7):2834-7. doi: 10.1016/j.transproceed.2013.03.047.
Hepatitis B (HBV) reactivation induced by chemotherapy is a problem currently encountered in the management of malignancies. HBV reactivation occurs particularly in patients who were not checked for HBV status, and therefore have not undergone antiviral prophylaxis. HBV reactivation may ultimately lead to fulminant liver failure (FLF). Liver transplantation (OLT), the only remaining effective treatment option, is generally denied for subjects with a recent history of malignancy.
We described retrospectively three cases of FLF caused by HBV reactivation in two men and one woman undergoing rituximab-containing chemotherapy for malignant lymphomas: follicular, diffuse large B-cell and lymphoplasmacytic types. The two men reactivated after eight cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone and the one woman after 13 cycles of rituximab monotherapy; their hematologic disease was in remission. All three patients were hepatitis B surface antigen (HBsAg)-positive with high HBV DNA levels. Neither man had been screened for HBV before chemotherapy; the woman had been treated with lamivudine (LAM) experiencing an HBV flare-up due to emergence of LAM resistance. All patients fulfilled King's College criteria for urgent OLT upon admission to the transplant center and underwent an urgent OLT. Their hemato-oncologic prognosis was considered to be favorable. All three patients are alive (54, 46, and 37 months post-transplantation), tumor-free and HBsAg negative on a standard HBV prophylaxis regimen: hepatitis B immunoglobulin and LAM + adefovir or tenofovir.
Before chemotherapy appropriate prophylaxis for HBV reactivation should always be administered to at-risk patients. However, if reactivation with FLF occurs, OLT should not be generally denied. The prognosis of the hematologic malignancy should be assessed; OLT should be considered for patients in remission with a favorable long-term prognosis, for our data suggest acceptable survival.
化疗诱导的乙型肝炎（HBV）再激活是目前恶性肿瘤治疗中遇到的一个问题。HBV再激活尤其发生在未检查HBV状态且因此未接受抗病毒预防的患者中。HBV再激活最终可能导致暴发性肝衰竭（FLF）。肝移植（OLT）是唯一剩下的有效治疗选择，但近期有恶性肿瘤病史的患者通常无法接受。
我们回顾性描述了3例因HBV再激活导致FLF的病例，其中2例男性和1例女性因恶性淋巴瘤接受含利妥昔单抗的化疗：滤泡型、弥漫性大B细胞型和淋巴浆细胞型。2例男性在接受8个周期的利妥昔单抗、环磷酰胺、阿霉素、长春新碱和泼尼松龙治疗后再激活，1例女性在接受13个周期的利妥昔单抗单药治疗后再激活；他们的血液系统疾病处于缓解期。所有3例患者乙型肝炎表面抗原（HBsAg）均为阳性，HBV DNA水平高。2例男性化疗前均未筛查HBV；该女性曾接受拉米夫定（LAM）治疗，因LAM耐药出现HBV复发。所有患者入院时均符合移植中心紧急OLT的国王学院标准，并接受了紧急OLT。他们的血液肿瘤预后被认为良好。所有3例患者均存活（移植后54、46和37个月），无肿瘤，在标准HBV预防方案（乙型肝炎免疫球蛋白和LAM+阿德福韦或替诺福韦）下HBsAg阴性。
化疗前应始终对高危患者进行适当的HBV再激活预防。然而，如果发生伴有FLF的再激活，一般不应拒绝OLT。应评估血液系统恶性肿瘤的预后；对于长期预后良好的缓解期患者应考虑进行OLT，因为我们的数据表明其生存率可以接受。
