HBsAg阳性弥漫大B细胞淋巴瘤化放疗后HBV再激活伴肝衰竭肝移植疗效个例报告

Efficacy of Liver Transplantation for Acute Hepatic Failure Caused by Reactivation of Hepatitis B Virus Infection after Chemotherapy and Radiotherapy for Diffuse Large B-Cell Lymphoma

本研究通过分析原发性胃非霍奇金淋巴瘤患者治疗过程,探讨HBsAg阳性原发胃弥漫大B细胞淋巴瘤化放疗后乙肝病毒(HBV)再激活伴肝衰竭肝移植治愈的患者骨髓形态、分子生物学和临床特点及治疗经验。应用骨髓细胞涂片观察骨髓细胞形态改变,多重巢式PCR检测异常基因表达和突变,实时荧光定量PCR(FQ-PCR)检测乙肝DNA含量。结果显示:患者发病时诊断为原发胃非霍奇金淋巴瘤,LUGANO分期Ⅰa期,aaIPI评分0分,低危,HbsAg(+),HBV DNA(-),为乙肝病毒携带者,胃大部分切除后予6个疗程R-CHOP方案(利妥昔单克隆抗体0.6 g,d0,环磷酰胺1.2 g d1,表柔比星90 mg d1,长春地辛4 mg d1,强的松90 mg d1-5)达完全缓解,利妥昔单克隆抗体(美罗华)0.6 g单药维持化疗2次,末次化疗结束时间2009年8月26日,2009年9月10日-10月10日行胃部调强适形放疗,共20次。化疗及放疗期间一直服用恩替卡韦,放疗结束后1周(即化疗后2个月)患者自行停用恩替卡韦,半年后出现HBV DNA(+)及肝功能衰竭,接受了亲缘右半肝移植治疗,至今仍存活。目前患者肝移植术后3年余,肝功能正常,HBsAg转阴,每3月复查PET-CT均为完全缓解(CR)。结论:HbsAg阳性的恶性淋巴瘤患者,尤其是应用利妥昔单抗的患者在治疗中应严密检测HBV DNA变化、肝功变化和乙肝再激活征象,化疗前和治疗过程中均进行抗病毒预防治疗,治疗后给予积极的抗病毒维持治疗,发生肝损害时应保肝和积极支持治疗,必要时可行肝移植以获得长期存活。

This study was aimed to investigate the morphological, biological , clinical and therapy features in a special case of primary gastric non-Hodgkin＇s lymphoma（PG-NHL） through amalysis of PG-NHL patient who developed fulminating hepatitis following chemotherapy and radiotherapy and thus received liver transplantation （LT）. The morphological changes of cells were analyzed by bone marrow smear, the expression and mutation of abnormal genes were detected by nested multiplex PCR, and HBV-DNA copies were detected by real-time fluorescence guantitative PCR （FQ-PCR）. The results showed that at onset of disease, patient was diagnosed as primary gastric non-Hodgkin＇s lymphoma （PG-NHL） with HBsAg（ ＋ ） and HBVDNA（ - ）. LUGANO stage was Ia. aalPI score was 0. The patient was treated with R-CHOP regimen （rituximab, cyclophosphamide, doxorubicin, vincristin and prednisolone）, rituximab maintenance treatment and radiotherapy. During the treatment, the patient has taken entecavir, 1 week later after the radiotherapy （2 months later after the chemotherapy）, then the entecavir was discontinued. Six months later HBV DNA （ ＋ ）, the progressive acute hepatic failure （AHF） happened to the patient, who thus received phylogenetic right liver transplantation （LT）. He has survived for 3 years after LT so far. The liver function of patient was normal more than 3 years after LT. The patient was checked regularly by PET-CT, and his PG-NHL continue complete remission（CR）. It is concluded that the patients receiving chemotherapy or immunosuppressive therapy should be screened for HBV DNA, liver function and HBV reactivation signs. HbsAg positive patients should receive preventive antiviral therapy. After chemotherapy or immunosuppressive therapy, the patients should be given antiviral maintenance therapy, and the liver damage should receive the hepatoprotective and effective support treatment, LT is necessary and feasible to obtain longterm survival.