原发性胆汁性肝硬化病理机制浅谈

王卫彬; 朱幼芙

doi:10.3969/j.issn.1001-5256.2013.11.002

原发性胆汁性肝硬化病理机制浅谈

DOI: 10.3969/j.issn.1001-5256.2013.11.002

南方医科大学南方医院肝病中心

详细信息

中图分类号: R575.22
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出版历程
- 收稿日期: 2013-07-30
- 出版日期: 2013-11-20

A brief discussion on pathogenesis of primary biliary cirrhosis

Institute of Hepatology, Nanfang Hospital, Southern Medical University

摘要

摘要: 原发性胆汁性肝硬化(PBC)发病机制未明,研究发现同卵双生共患PBC概率较高,而其家族聚集性,全基因组关联分析(GWAS)结果皆表明了遗传因素的重要性;流行病学调查和动物模型实验则表明生物异源物质和感染性分子可能通过分子模拟在发病中起作用;而如下证据则支持其自身免疫机制:出现高度特异性的血清抗线粒体抗体(AMA)和自身反应性T淋巴细胞;就组织病理学而言,PBC的特征为汇管区炎症和免疫介导的肝内胆管破坏。从遗传因素、环境暴露、自身免疫、肝脏病理对PBC的病理机制进行了总结,指出了免疫失衡的重要性。
- 肝硬化,胆汁性 /
- 自身免疫疾病 /
- 疾病遗传易感性 /
- 环境暴露 /
- 病理过程
Abstract: The pathogenesis of primary biliary cirrhosis ( PBC) is unknown. Researchers have found that monozygotic twins have a higher concordance rate for PBC than dizygotic twins, and the phenomenon of familial aggregation and the results of genome- wide association studies also demonstrate the importance of genetic factors in the pathogenesis of PBC. The epidemiological investigations and animal model experiments show that xenobiotics and infectious molecules may play a role in the pathogenesis of PBC by molecular mimicry. The appearance of highly specific serum antimitochondrial antibodies and autoreactive T cells suggests a possible autoimmune pathogenesis of PBC. The histopathological features of PBC are inflammation in the portal area and immune- mediated intrahepatic bile duct destruction. The pathogenesis of PBC is summarized from the aspects of genetic factors, environmental exposure, autoimmune response, and liver pathology, and the importance of immune imbalance is emphasized.
- liver cirrhosis, biliary /
- autoimmune diseases /
- genetic predisposition to disease /
- environmental exposure /
- pathologic processes

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参考文献(1)

[1]LLEO A, OERTELT-PRIGIONE S, BIANCHI I, et al.Y chromosome loss in male patients with primary biliary cirrhosis[J].J Autoimmun, 2013, 41:87-91.[2]SELMI C, MAYO MJ, BACH N, et al.Primary biliary cirrhosis in monozygotic and dizygotic twins:genetics, epigenetics, and environment[J].Gastroenterology, 2004, 127 (2) :485-492.[3]Hirschfield GM, Invernizzi P.Progress in the genetics of primary biliary cirrhosis[J].Semin Liver Dis, 2011, 31 (2) :147-156.[4]LI Q, WANG B, PAN F, et al.Association between cytotoxic T-lymphocyte antigen 4 gene polymorphisms and primary biliary cirrhosis in Chinese population:data from a multicenter study[J].J Gastroenterol Hepatol, 2013, 28 (8) :1397-1402.[5]MANTAKA A, GOULIELMOS GN, KOULENTAKI M, et al.Polymorphisms of genes related to endothelial cells are associated with primary biliary cirrhosis patients of cretan origin[J].Hum Immunol, 2012, 73 (8) :829-835.[6]INAMINE T, HIGA S, NOGUCHI F, et al.Association of genes involved in bile acid synthesis with the progression of primary biliary cirrhosis in Japanese patients[J].J Gastroenterol, 2013 Jan 11.[Epub ahead of print][7]KIMURA Y, SELMI C, LEUNG PS, et al.Genetic polymorphisms influencing xenobiotic metabolism and transport in patients with primary biliary cirrhosis[J].Hepatology, 2005, 41 (1) :55-63.[8]LAMMERTC, NGUYEN DL, JURAN BD, et al.Queationaire based assessment of risk factors for primary biliary cirrhosis[J].Dig Liver Dis, 2013, 45 (7) :589-594.[9]SHAPIRA Y, AGMON-LEVIN N, RENAUDINEAU Y, et al.Serum markers of infections in patients with primary biliary cirrhosis:evidence of infection burden[J].Exp Mol Pathol, 2012, 93 (3) :386-390.[10]MOHAMMED JP, FUSAKIO ME, RAINBOW DB, et al.Identification of Cd101 as a susceptibility gene for Novosphingobium a romaticivorans-induced liver autoimmunity[J].J Immunol, 2011, 187 (1) :337-349.[11]MASON AL.The evidence supports a viral aetiology for pimary biliary cirrhosis[J].J Hepatol, 2011, 54 (6) :1312-1314.[12]XU L, SHEN Z, GUO L, et al.Does a betaretrovirus infection trigger primary biliary cirrhosis?[J].Proc Natl Acad Sci U S A, 2003, 100 (14) :8454-8459.[13]NAIYANETR P, BUTLER JD, MENGL, et al.Electrophile-modified lipoic derivatives of PDC-E2 elicits anti-mitochondrial antibody reactivity[J].J Autoimmun, 2011, 37 (3) :209-216.[14]SELMI C, BOWLUS CL, GERSHWIN ME, et al.Primary biliary cirrhosis[J].Lancet, 2011, 377 (9777) :1600-1609.[15]BOGDANOS DP, INVERNIZZI P, MACKAY IR, et al.Autoimmune liver serology:current diagnostic and clinical challenges[J].World J Gastroenterol, 2008, 14 (21) :3374-3387.[16]SASAKI M, MIYAKOSHI M, SATO Y, et al.Increased expression of mitochondrial proteins associated with autophagy in biliary epithelial lesions in primary biliary cirrhosis[J].Liver Int, 2013, 33 (2) :312-320.[17]LAN RY, SALUNGA TL, TSUNEYAMA K, et al.Hepatic IL-17responses in human and murine primary biliary cirrhosis[J].J Autoimmun, 2009, 32 (1) :43-51.[18]LAN RY, CHENG C, LIAN ZX, et al.Liver-targeted and peripheral blood alterations of regulatory T cells in primary biliary cirrhosis[J].Hepatology, 2006, 43 (4) :729-737.[19]BERNUZZI F, FENOGLIO D, BATTAGLIA F, et al.Phenotypical and functional alterations of CD8 regulatory T cells in primary biliary cirrhosis[J].J Autoimmun, 2010, 35 (3) :176-180.[20]LLEO A, BOWLUS CL, YANG GX, et al.Biliary apotopes and anti-mitochondrial antibodies activate innate immune responses in primary biliary cirrhosis[J].Hepatology, 2010, 52 (3) :987-998.[21]YOU ZR, WANG QX, BIAN ZL, et al.The immunopathology of liver granulomas in primary biliary cirrhosis[J].J Autoimmun, 2012, 39 (3) :216-221.[22]GRAHAM RP, SMYRK TC, ZHANG L, et al.Evaluation of langerhans cell infiltrate by CD1a immunostain in liver biopsy for the diagnosis of primary biliarycirrhosis[J].Am J Surg Pathol, 2012, 36 (5) :732-736.[23]KAKUDA Y, HARADA K, SAWADA-KITAMURA S, et al.Evaluation of a new histologic staging and grading system for primary biliary cirrhosis in comparison with classical systems[J].Hum Patho, 2013, 44 (6) :1107-1117.[24]DREBBER U, MUELLER JJ, KLEIN E, et al.Liver biopsy in primary biliary cirrhosis:Clinicopathological data and stage[J].Pathol Int, 2009, 59 (8) :546-554.[25]ALEMPIJEVIC T, KRSTIC M, JESIC R, et al.Biochemical markers for non-invasive assessment of disease stage in patients with primary biliary cirrhosis[J].World J Gastroenterol, 2009, 15 (5) :591-594.[26]MA JL, WANG R, ZHANG FK, et al.A noninvasive diagnostic model of liver fibrosis using serum markers in primary biliary cirrhosis[J].Chin J Int Med, 2012, 51 (8) :618-622. (in Chinese) 马佳丽, 王蕊, 张福奎, 等.原发性胆汁性肝硬化无创性肝纤维化诊断模型的建立[J].中华内科杂志, 2012, 51 (8) :618-622.[27]INVERNIZZI P, CROSIGNANI A, BATTEZZATI PM, et al.Comparison of the clinical features and clinical course of antimitochondrial antibody-positive and-negative primary biliary cirrhosis[J].Hepatology, 1997, 25 (5) :1090-1095.[28]DANIELS JA, TORBENSON M, ANDERS RA, et al.Immunostaining of plasma cells in primary biliary cirrhosis[J].Am J Clin Pathol, 2009, 131 (2) :243-249.[29]TU CT, HAN B, ZHANG SC.Clinical and histological characteristics of the primary biliary cirrhosis and autoimmune hepatitis overlap sydrome:a retrospective study[J].Chin J Gasteroenterol Hepatol, 2010, 19 (2) :166-169. (in Chinese) 涂传涛, 韩冰, 张顺财.PBC-AIH重叠综合征临床与病理特征:一项回顾性研究[J].胃肠病学和肝脏病学杂志, 2010, 19 (2) :166-169.[30]BARAKAUSKIENE·A, SPEICˇIEN E·D, LIAKINA V, et al.Expression of cytokeratin 7 as a histological marker of cholestasis and stages of primary biliary cirrhosis[J].Medicina, 2011, 47 (1) :31-38.[31]KUMAGI T, GUINDI M, FISCHER SE, et al.Baseline ductopenia and treatment response predict long-term histological progression in primary biliarycirrhosis[J].AM J Gastroenterol, 2010, 105 (10) :2186-2194.[32]DUAN WJ, JIA JD.Review of clinical improvements in autoimmune liver diseases2010[J].J Clin Hepatol, 2011, 27 (6) :567-569. (in Chinese) 段维佳, 贾继东.2010年自身免疫性肝病临床进展回顾[J].临床肝胆病杂志, 2011, 27 (6) :567-569.

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