肝脏活检在异基因造血干细胞移植中的应用

目的评价肝脏活检在异基因造血干细胞移植（Allo—HSCT）后肝功能损害患者中的诊断及治疗意义。方法病例选自北京大学人民医院血液病研究所1999年2月至2004年1月所做的10例Allo—HSCT并接受肝脏活检的患者,男5例,女5例。年龄15～56岁（中位34．5岁）。其中白血病8例,骨髓异常增生综合征1例,重症再生障碍性贫血1例。移植方式包括非血缘骨髓移植1例,同胞全相合Allo—HSCT6例,单倍体移植1例,脐带血移植2例。预处理方案,采用全身照射加环磷酰胺2例,非全身照射方案8例。移植物抗宿主病全部采用环胞菌素A加短程甲氨蝶呤加霉酚酸酯方案。移植前供受者常规接受肝功能及乙肝、丙肝病毒检测。10例患者均接受经皮肝穿刺活检,得到肝组织标本分别经苏木素-伊红和Masson染色在光学显微镜下观察及免疫组织化学检测。结果10例患者Allo—HSCT后出现肝功能损害的时间为2～5个月,中位3．8个月。移植前7例患者HBV、HCV检测阳性,移植后仍阳性。移植前后3例患者HBV、HCV检测全部阴性,临床诊断为移植物抗宿主病（GVHD）肝损害。10例患者在出现肝功能损害时,9例伴有不同程度慢性GVHD（cGVHD）其他表现。10例患者均根据临床诊断采用初始治疗后,肝功能改善不好。分别于Allo—HSCT后4～12个月（中位5．5个月）行肝脏活检。病理结果3例肝炎病毒阴性者为cGVHD肝损害,其余7例为肝炎病毒感染合并cGVHD肝损害。3例单纯诊断为cGVHD肝损害患者,经调整抗GVHD药物后,肝功能恢复;其余7例患者采用抗病毒及调整免疫抑制剂等综合治疗,结果2例肝功能恢复并存活。5例死亡,其中2例在治疗中肝功能改善不好,因合并肺部感染死亡,3例因肝功能衰竭,肝昏迷死亡。结论Allo—HSCT后,对于临床诊断肝脏GVHD肝损害而治疗效果不好的患者,肝脏活检可起到鉴别诊断和指导进一步治疗的作用。肝炎病毒感染与GVHD肝损害合并存在者预后差。肝活检对指导治疗具有一定局限性,还需结合临床及病理制订治疗方案。

Liver biopsy in the management of liver dysfunction after allogeneic hematopoietic stem-cell transplantation

Objective To investigate the pathologic and clinical characteristics of patients with liver dysfunction after allogeneic hemopoietic stem cell transplantation (Allo-HSCT), and evaluate the role of liver biopsy in diagnosis and management of liver dysfunction post Allo-HSCT. Methods Ten patients with hematological diseases, 5 males and 5 females, aged 34.5 (15-56), underwent Allo-HSCT, 6 receiving Allo-HSCT from their HLA-matched siblings, one receiving haploidentical transplant, two receiving cord blood transplantation from sibling, and one receiving unrelated BMT. The conditioning regimens included Cy/TBI (in 2 cases), and non-TBI regimen (in 8 cases). All the patients received cyclosporine A, short term MTX and MMF for the prophylaxis of graft-versus-host disease (GVHD). Test of liver function and examination of HBV and HCV related serologic markers were performed for the patients and recipients before transplantation and for those who had liver dysfunction after transplantation. Percutaneous liver biopsy was performed for these 10 patients. Biopsy specimens were examined histologically by hemaoxylin-eosin staining, Masson staining and immunohistochemical stating of related viruses. Results All 10 patients showed liver dysfunction on average 3.5 months (2-5 months) after the transplantation. Seven patients positive in HBV and HCV serologic markers before HSCT remained positive after the transplantation. Three patients negative in HBV/HCV markers before and after Allo-HSCT were diagnosed as with GVHD clinically. Eight patients had other manifestations of chronic GVHD. Eight patients received liver biopsy 5.5 months (4-12 months) because of poor improvement in the initial treatment stage. The result of biopsy showed hepatic GVHD in 3 patients and hepatic GVHD concomitant with HBV or HCV hepatitis reactivation in 7 patients. The liver function of 3 patients diagnosed as with hepatic GVHD returned to normal after the use of the second-line anti-GVHD therapy. The other 7 patients used anti-virus agents combined with immunosuppressive agents with the result that 2 patients remained alive with normal liver function and 5 patients died due to pulmonary complication (2 cases) or hepatic failure and hepatic coma (3 cases). Conclusion Liver biopsy is of distinguished diagnostic value for patients with refractory hepatic GVHD after Allo-HSCT. The prognosis is poor for patients having hepatic GVHD concomitant with active hepatic virus infection. At this time the role of liver biopsy is limited and management should be made according to the clinical features and liver pathology.