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2.肝炎病毒在感染者体内的准种特性及其意义。
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参考文献
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[1] 刘克洲,陈智主编.人类病毒性疾病.北京:人民卫生出版社,2002.
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[2] 成军.乙型肝炎病毒基因组结构与功能复杂性的研究进展.世界华人消化杂志,2003,11
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[3] Dienstag JL. Hepatitis B virus infection. N Engl J Med, 2008, 2
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[4] Liu CJ, Kao JH. Genetic variability of hepatitis B virus and response to antiviral therapy. Antivir Ther, 2008, 13(5)
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[5] Khuroo MS, Khuroo MS. Hepatitis E virus. Curr Opin Infect Dis, 2008, 21(5)
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[6] Reshetnyak VI, Karlovich TI, Ilchenko LU. Hepatitis G virus. World J Gastroenterol, 2008, 14(30)
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[7] Gatta A, Giannini C, Lampertico P, et al. Hepatotropic viruses: new insights in pathogenesis and treatment. Clin Exp Rheumatol, 2008, 26(1 Suppl 48)
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(刘克洲 沃健儿)
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内科学新进展 第四节 内毒素与肝病
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摘 要 内毒素血症(endotoxaemia, ETM)分外源性及内源性两大类,前者多因革兰阴性菌感染或输入含内毒素的液体、腹水或血液引起,后者则因肝病肠道微生态失衡、肠道细菌过度生长、肠道屏障受损、肠道细菌及内毒素过量易位,而肝脏单核巨噬细胞系统功能低不能有效清除来自肠道内毒素等因素引起。在肝病尤其是重型肝病易发生内毒素血症,后者又可加重肝脏损害,并引起各种肝外并发症。肠道选择性脱污染、应用微生态调节剂、合理应用抗生素及人工肝治疗是预防治疗肝病内毒素血症的有效方法。
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Abstract Endotoxaemia(ETM)includes extraneous and endogenous ETM. The main causes of the former(extraneous ETM)are both Gram negative bacteria(GNB)infections, infusion of fluid contained endotoxin, re-infusion of contaminated ascites and blood. Endogenous ETM are the common complication in liver diseases, especially in severe hepatic diseases. On one hand, patients with liver diseases always having gut microbiological imbalance, bacterial overgrowth, damaged barrier of intestinal wall, which could lead to the intestinal bacteria(including endotoxin, etc)translocation, On the other hand, the dysfunction of kupffer cell make the liver could not clear effectively the overfull translocate endotoxin from intestine, ETM of liver diseases is connected with the above factors. As the complication of liver diseases, ETM can further both the hepatic injury and other extra-hepatic complications such as hemorrhage of digestive tract, hepatorenal syndrome, and so on. Intestinal selected decomtamination(ISD), administration of prebiotics, probiotics, synbiotics, rational administration of antibiotics and artificial liver support system are the effective prevention and therapy methods for ETM in liver diseases.
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各种肝病,有原发性因素,如病毒、药物、酒精、肝癌等;也有继发性因素,即在原有肝病的基础上,某些因素可促进与加重肝脏损害,内毒素血症是多种继发因素之一。内毒素血症(endotoxaemia, ETM)分外源性及内源性两大类,前者多因革兰阴性菌感染或输入含内毒素的液体、腹水或血液引起,后者则因肝病使单核巨噬细胞系统功能降低等因素,不能有效清除来自肠道的内毒素所引起。早在1936年曾有人推测某种细菌因子在肝病的发病过程中具有致病因子,自70年代将鲎试验用于临床检测内毒素血症以来,国内外对各种肝病内毒素血症的有关问题进行了广泛的研究和有价值的探讨,使内毒素血症与肝病关系的研究日趋深入。许多研究资料证明,肝病尤其是重型肝病易发生内毒素血症,后者又可加重肝脏损害,并引起各种肝外并发症,如急性胃黏膜糜烂、弥漫性血管内凝血、肾功能衰竭等,往往成为致死的原因。
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一、各种肝病时内毒素血症发生率
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各种肝病内毒素血症发生率国内外报道不一,在严重肝病时,往往出现内毒素血症,其发生率见表9-1。
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表9-1 各种肝病的内毒素血症(%)
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二、肝病发生内毒素血症的机理
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内毒素源自革兰阴性杆菌。肠道是人体最大的贮菌库,含大量革兰阴性杆菌,肠道也是人体最大的内毒素池。在正常人,门静脉血可因肠道微量内毒素易位(endotoxin translocation)而存在门静脉内毒素血症,门静脉血中存在的微量内毒素是一种生理现象,起免疫调节剂(immunomodulator)作用。一般肝脏清除内毒素能力很强,进入肝脏的内毒素几乎全被肝脏单核巨噬细胞系统吞噬清除,故不引起内毒素血症。
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肝病尤其是重型肝炎极易并发细菌、真菌感染及内毒素血症。英国皇家医学院的一项急性肝衰竭并发感染的前瞻性研究发现,50例急性肝衰竭患者中80%患者并发细菌感染,真菌感染者达32%,其中10例经细菌学检查证实为大肠杆菌状细菌(coliform),如大肠埃希杆菌、不动杆菌、肺炎克雷伯杆菌等。李兰娟的一项研究则提示暴发性肝衰竭并发内毒素血症者达88.9%,也有的报道达100%。革兰阴性菌感染固然可以伴有内毒素血症,但重型肝炎及肝硬化高达90%~100%的内毒素血症发生率难以用革兰阴性菌感染来解释。
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肝病发生内毒素血症与下述因素有关。
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(一)肠道内毒素产生和易位增加
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