Immunohistochemical evidence of disease recurrence after liver transplantation for primary biliary cirrhosis.
Immunohistochemical evidence of disease recurrence after liver transplantation for primary biliary cirrhosis.
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原发性胆汁性肝硬化肝移植后疾病复发的免疫组织化学证据。
DOI：
10.1002/hep.510240517
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Gershwin,ME
中科院分区：
文献类型：
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作者：
VandeWater,J;Gerson,LB;Ferrell,LD;Lake,JR;Coppel,RL;Batts,KP;Wiesner,RH;Gershwin,ME
肝移植后原发性胆汁性肝硬变(PBC)是否复发一直是一个有趣且有争议的问题；排斥反应、病毒性肝炎和药物效应都可能在组织学和生化上与复发的PBC相似。此外，缺乏可靠的PBC复发的临床标准。在这项研究中，使用一种特性良好的单抗(MAb)C355.1与PBC(丙酮酸脱氢酶复合体[PDC-E2])的免疫优势线粒体自身抗原反应来研究疾病复发的问题。当用于免疫组织化学分析时，C355.1在PBC患者的肝脏切片上产生强烈的胆管上皮细胞尖端染色，可能是PBC最早的已知标记物。对67例原位肝移植(OLT)前后肝活检标本进行了免疫组织化学和组织学分析，其中PBC组38例，非PBC组29例。切片用单抗C355.1或对照单抗C315染色，并分析移植后活组织标本胆管中是否有根尖反应性复发。免疫组织化学染色与活检时的组织学结果和血清生化指标相关。我们的数据表明，大量接受PBC移植的患者(28/38)而不是对照组(0/29)出现了肝胆管上皮单抗C355.1的染色模式，与移植前的模式没有区别。28例患者中，8例为复发性PBC，2例为慢性排斥，2例为急性排斥，9例为非特异性改变，4例为正常或接近正常，3例为其他组织学改变。仅50%心尖部C355.1染色的患者有胆汁淤积的肝酶水平。因此，似乎有免疫组织化学证据支持原位肝移植后PBC复发的概念。在疾病临床出现之前出现胆管上皮异常不仅对肝移植很重要，而且对了解PBC的自然病程也很重要。
Whether primary biliary cirrhosis (PBC) recurs after liver transplantation has remained an interesting and controversial issue; rejection, viral hepatitis, and drug effects all may mimic recurrent PBC histologically and biochemically. Furthermore, reliable clinical criteria for PBC recurrence are lacking. In this study, the issue of disease recurrence using a well‐characterized monoclonal antibody (MAb), C355.1, that reacts with the immunodominant mitochondrial autoantigen of PBC (pyruvate dehydrogenase complex [PDC‐E2]) was addressed. When used in an immunohistochemical assay, C355.1 produces intense apical staining of bile duct epithelium specifically in liver sections of patients with PBC and may be the earliest known marker of PBC. Immunohistochemical and histological analysis of serial liver biopsy specimens of 67 patients pre‐ and post‐orthotopic liver transplantation (OLT), including 38 patients with PBC and 29 non‐PBC liver disease controls, was performed. Sections were stained with MAb C355.1 or the control MAb C315 and analyzed to determine whether there was a recurrence of apical reactivity in the bile ducts of the posttransplantation biopsy specimens. The immunohistochemical staining was correlated with the histological findings and serum biochemistries at the time of the biopsy. Our data indicate that a significant number of patients who underwent transplantation for PBC (28 of 38) but not controls (0 of 29) develop a staining pattern of liver bile duct epithelium with MAb C355.1 that is indistinguishable from the pretransplantation pattern. Of the 28 patients with this apical staining pattern, 8 were characterized histologically as possible recurrent PBC, 2 as chronic rejection, 2 as acute rejection, 9 as nonspecific changes, 4 as normal or near normal, and 3 had other histological changes. Only 50% of the patients with apical C355.1 staining had liver enzyme levels suggestive of cholestasis. Thus, there appears to be immunohistochemical evidence that supports the concept of recurrence of PBC after OLT. The appearance of biliary epithelial abnormalities before the clinical appearance of disease is important not only for liver transplantation but also for understanding the natural history of PBC.