Van de Water J, Gerson L B, Ferrell L D, Lake J R, Coppel R L, Batts K P, Wiesner R H, Gershwin M E
Department of Rheumatology, Allergy and Clinical Immunology, School of Medicine, University of California Davis, USA.
Hepatology. 1996 Nov;24(5):1079-84. doi: 10.1002/hep.510240517.
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.
原发性胆汁性肝硬化（PBC）在肝移植后是否复发一直是一个有趣且有争议的问题；排斥反应、病毒性肝炎和药物作用在组织学和生化方面都可能与复发性PBC相似。此外，目前还缺乏用于诊断PBC复发的可靠临床标准。在本研究中，我们使用一种特性明确的单克隆抗体（MAb）C355.1来探讨疾病复发问题，该抗体可与PBC的免疫显性线粒体自身抗原（丙酮酸脱氢酶复合物[PDC-E2]）发生反应。当用于免疫组织化学检测时，C355.1在PBC患者的肝切片中可使胆管上皮产生强烈的顶端染色，它可能是已知最早的PBC标志物。我们对67例原位肝移植（OLT）前后患者的系列肝活检标本进行了免疫组织化学和组织学分析，其中包括38例PBC患者和29例非PBC肝病对照。切片用MAb C355.1或对照MAb C315染色，并进行分析以确定移植后活检标本的胆管中是否出现顶端反应性复发。免疫组织化学染色结果与活检时的组织学发现及血清生化指标相关。我们的数据表明，大量接受PBC移植的患者（38例中的28例），而非对照组患者（29例中的0例），其肝内胆管上皮细胞经MAb C355.1染色后呈现出与移植前无法区分的染色模式。在这28例具有顶端染色模式的患者中，8例组织学特征为可能的复发性PBC，2例为慢性排斥反应，2例为急性排斥反应，9例为非特异性改变，4例正常或接近正常，3例有其他组织学改变。仅有50%顶端C355.1染色的患者肝酶水平提示胆汁淤积。因此，似乎有免疫组织化学证据支持OLT后PBC复发的概念。胆管上皮异常在疾病临床表现出现之前出现，这不仅对肝移植很重要，而且对于理解PBC的自然病程也很重要。
