De novo hepatitis with autoimmune antibodies and atypical histology - A rare cause of late graft dysfunction after pediatric liver transplantation
De novo hepatitis with autoimmune antibodies and atypical histology - A rare cause of late graft dysfunction after pediatric liver transplantation
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DOI：
10.1097/00007890-200103150-00016
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发表时间：
2001-03-15
期刊：
影响因子：
6.2
通讯作者：
Brady, L
中科院分区：
文献类型：
--
作者：
Gupta, P;Hart, J;Brady, L
背景原位肝移植术后的晚期移植物功能障碍通常是由于慢性排斥反应、原发病复发、败血症、淋巴组织增生性疾病或血管或胆道并发症。在此，我们描述了一个儿科肝移植患者的子集，其中晚期移植物功能障碍与自身免疫标志物、胆管增生和门静脉浸润相关，后者进展为纤维化。115名儿童中的6名在移植后随访了5年以上，出现了这种不寻常的移植物功能障碍。这些儿童正在接受低剂量单一免疫抑制治疗（平均环孢菌素谷浓度89 μ g/L），并逐渐减少类固醇激素的使用，中位持续时间为1.5年。所有患儿均行肝活检以评估移植物功能障碍，并由有经验的肝脏病理学家解释组织学结果。所有患者均检测丙型肝炎病毒抗体、B型肝炎表面抗原和甲型肝炎IgM抗体。所有患者均在移植物功能障碍发生时进行超声检查，其中3例组织学上胆管明显增生的患者进行了胆管造影。所有患者的组织学检查均显示汇管区单核细胞浸润，伴界面肝炎、汇管区纤维化和导管增生，无导管损伤或丢失。所有6例患者的抗核抗体或平滑肌抗体滴度均为阳性，所有患者的甲型、B和丙型肝炎病毒研究均为阴性。根据国际自身免疫性肝炎组评分系统，5例患者在移植物功能障碍发作时可能患有自身免疫性肝炎（评分10-15），1例患者患有明确的自身免疫性肝炎（评分>15）。然而，尽管积极的治疗，4例患者发展桥接门静脉纤维化导致移植物loss in two patients.Conclusion，这种临床星座是与更糟糕的结果，然后先前描述的移植后新生自身免疫性肝炎的儿科患者。需要进一步的研究来为这些患者找到最佳的治疗方案。
Background. Late graft dysfunction after orthotopic liver transplantation is commonly due to chronic rejection, recurrence of primary disease, sepsis, lymphoproliferative disease, or vascular or biliary complications. Herein we describe a subset of pediatric liver transplant patients in whom late graft dysfunction was associated with autoimmune markers, bile ductular proliferation, and portal infiltrates, which progress to fibrosis, This subset of patients has not been previously described.Methods. Six of the 115 children followed for greater than 5 years after transplantation developed this unusual form of graft dysfunction, Ah children were on a low-dose single immunosuppressive therapy (mean trough cyclosporine concentration 89 mug/L) and had been tapered off steroids for a median duration of 1.5 year. Liver biopsies were performed in all children to evaluate the graft dysfunction, and the histologic findings were interpreted by an experienced hepato-pathologist, All patients were tested for antibodies to hepatitis C virus, hepatitis B surface antigen, and IgM antibodies to hepatitis A Smooth muscle antibody, antinuclear antibody, and antibody to liver/kidney microsome type 1 were sought by indirect immunofluorescence, International Autoimmune Hepatitis Group scores were calculated, All patients underwent ultrasonography with doppler studies at the onset of graft dysfunction, Three patients with marked bile duct proliferation on histology had cholangiograms.Results. Histology in all patients showed mononuclear cell infiltrates in the portal area with interface hepatitis, portal fibrosis, and ductular proliferation without duct damage or loss. All six patients had positive antinuclear antibody or smooth muscle antibody titers, Viral studies for hepatitis A, B, and C were negative in all patients. On the International Autoimmune Hepatitis Group scoring system, five patients had probable autoimmune hepatitis (score of 10-15) and one had definite autoimmune hepatitis (score >15) at the onset of graft dysfunction, Ah were treated with azathioprine and prednisone similar to treatment for autoimmune hepatitis. However, despite aggressive treatment, four patients developed bridging portal fibrosis resulting in graft loss in two patients.Conclusion, This clinical constellation is associated with worse outcome then that previously described for pediatric patients with posttransplantation de novo autoimmune hepatitis. Further studies are needed to find an optimal treatment regimen for these patients.