慢性乙型肝炎及肝硬化患者肝脏微循环改变

为探讨慢性乙型肝炎(慢乙肝)及肝硬化患者的肝脏微循环状态.对141例慢乙肝、12例肝硬化患者和2例正常人的肝组织进行HE染色,光镜观察,并对其中53例慢乙肝和2例肝硬化患者的肝组织进行了电镜观察.结果显示,正常人的肝窦腔通畅,无狭窄或闭塞,无红细胞聚集现象.慢乙肝患者86.52%有肝窦腔狭窄,60.28%肝窦腔内见红细胞聚集,34.04%肝窦腔内有血栓形成;电镜观察见94.34%的患者肝窦内皮细胞窗孔减小减少,33.96%有基底膜形成,24.53%狄氏腔内出现胶原纤维.肝硬化患者肝组织结构紊乱,肝腺泡消失,假小叶形成.提示慢乙肝患者存在肝脏微循环障碍,肝硬化时肝脏微循环结构丧失.     

慢性乙型肝炎患者肝组织低氧诱导因子1α的表达变化

目的研究肝组织中低氧诱导因子（HIF）-1α的表达与慢性乙型肝炎（CHB）患者肝脏微循环障碍的关系。方法对81例CHB患者和5例正常人的肝标本进行免疫组织化学染色,并用透射电镜观察肝组织超微结构的变化。结果 HIF-1α在肝组织中的表达强度和范围与CHB患者肝脏微循环障碍程度密切相关,电镜示肝窦腔内红细胞聚集、狄氏腔中胶原纤维沉积及肝窦内皮细胞表面有基底膜形成。结论 HIF-1α通过激活血管增生,最终导致血管纤维化和肝窦毛细血管化,加重肝脏微循环障碍。     

从组织病理学角度探讨慢性乙型肝炎肝纤维化的发生

目的 探讨窦内皮细胞在肝纤维化发生中的作用,以及肝脏微循环障碍、肝窦毛细血管化与肝纤维化发生的关系. 方法对56例慢性乙型肝炎患者进行肝活组织枪查,将肝组织分成两部分,分别通过HE染色进行光学显微镜观察,以及常规制作电子显微镜标本在透射电子显微镜下进行超微结构观察.结果 56例慢性乙型肝炎患者中,轻度39例,中度10例,重度7例.慢性乙型肝炎患者肝星状细胞的形态类似成纤维细胞,周围有胶原纤维形成.窦内皮细胞与肝星状细胞间有电子致密物沉积.其中53例窦内皮细胞窗孔有不同程度的减少,减小,20例见窦内皮细胞下有连续或不连续的膜样物质形成,15例狄氏腔内有胶原纤维沉积.15例肝功能正常患者有的肝窦腔内有红细胞聚集,严重者有微血栓形成. 结论窦内皮细胞通过与肝星状细胞作用,从而参与肝纤维化的发生.肝脏微循环障碍、肝窦毛细血管化是肝纤维化的早期重要病理改变.     

从组织病理学角度探讨慢性乙型肝炎肝纤维化的发生

目的 探讨窦内皮细胞在肝纤维化发生中的作用,以及肝脏微循环障碍、肝窦毛细血管化与肝纤维化发生的关系. 方法对56例慢性乙型肝炎患者进行肝活组织枪查,将肝组织分成两部分,分别通过HE染色进行光学显微镜观察,以及常规制作电子显微镜标本在透射电子显微镜下进行超微结构观察.结果 56例慢性乙型肝炎患者中,轻度39例,中度10例,重度7例.慢性乙型肝炎患者肝星状细胞的形态类似成纤维细胞,周围有胶原纤维形成.窦内皮细胞与肝星状细胞间有电子致密物沉积.其中53例窦内皮细胞窗孔有不同程度的减少,减小,20例见窦内皮细胞下有连续或不连续的膜样物质形成,15例狄氏腔内有胶原纤维沉积.15例肝功能正常患者有的肝窦腔内有红细胞聚集,严重者有微血栓形成. 结论窦内皮细胞通过与肝星状细胞作用,从而参与肝纤维化的发生.肝脏微循环障碍、肝窦毛细血管化是肝纤维化的早期重要病理改变.     

从组织病理学角度探讨慢性乙型肝炎肝纤维化的发生

目的 探讨窦内皮细胞在肝纤维化发生中的作用,以及肝脏微循环障碍、肝窦毛细血管化与肝纤维化发生的关系. 方法对56例慢性乙型肝炎患者进行肝活组织枪查,将肝组织分成两部分,分别通过HE染色进行光学显微镜观察,以及常规制作电子显微镜标本在透射电子显微镜下进行超微结构观察.结果 56例慢性乙型肝炎患者中,轻度39例,中度10例,重度7例.慢性乙型肝炎患者肝星状细胞的形态类似成纤维细胞,周围有胶原纤维形成.窦内皮细胞与肝星状细胞间有电子致密物沉积.其中53例窦内皮细胞窗孔有不同程度的减少,减小,20例见窦内皮细胞下有连续或不连续的膜样物质形成,15例狄氏腔内有胶原纤维沉积.15例肝功能正常患者有的肝窦腔内有红细胞聚集,严重者有微血栓形成. 结论窦内皮细胞通过与肝星状细胞作用,从而参与肝纤维化的发生.肝脏微循环障碍、肝窦毛细血管化是肝纤维化的早期重要病理改变.     

从组织病理学角度探讨慢性乙型肝炎肝纤维化的发生

目的 探讨窦内皮细胞在肝纤维化发生中的作用,以及肝脏微循环障碍、肝窦毛细血管化与肝纤维化发生的关系. 方法对56例慢性乙型肝炎患者进行肝活组织枪查,将肝组织分成两部分,分别通过HE染色进行光学显微镜观察,以及常规制作电子显微镜标本在透射电子显微镜下进行超微结构观察.结果 56例慢性乙型肝炎患者中,轻度39例,中度10例,重度7例.慢性乙型肝炎患者肝星状细胞的形态类似成纤维细胞,周围有胶原纤维形成.窦内皮细胞与肝星状细胞间有电子致密物沉积.其中53例窦内皮细胞窗孔有不同程度的减少,减小,20例见窦内皮细胞下有连续或不连续的膜样物质形成,15例狄氏腔内有胶原纤维沉积.15例肝功能正常患者有的肝窦腔内有红细胞聚集,严重者有微血栓形成. 结论窦内皮细胞通过与肝星状细胞作用,从而参与肝纤维化的发生.肝脏微循环障碍、肝窦毛细血管化是肝纤维化的早期重要病理改变.     

从组织病理学角度探讨慢性乙型肝炎肝纤维化的发生

目的 探讨窦内皮细胞在肝纤维化发生中的作用,以及肝脏微循环障碍、肝窦毛细血管化与肝纤维化发生的关系. 方法对56例慢性乙型肝炎患者进行肝活组织枪查,将肝组织分成两部分,分别通过HE染色进行光学显微镜观察,以及常规制作电子显微镜标本在透射电子显微镜下进行超微结构观察.结果 56例慢性乙型肝炎患者中,轻度39例,中度10例,重度7例.慢性乙型肝炎患者肝星状细胞的形态类似成纤维细胞,周围有胶原纤维形成.窦内皮细胞与肝星状细胞间有电子致密物沉积.其中53例窦内皮细胞窗孔有不同程度的减少,减小,20例见窦内皮细胞下有连续或不连续的膜样物质形成,15例狄氏腔内有胶原纤维沉积.15例肝功能正常患者有的肝窦腔内有红细胞聚集,严重者有微血栓形成. 结论窦内皮细胞通过与肝星状细胞作用,从而参与肝纤维化的发生.肝脏微循环障碍、肝窦毛细血管化是肝纤维化的早期重要病理改变.     

从组织病理学角度探讨慢性乙型肝炎肝纤维化的发生

目的 探讨窦内皮细胞在肝纤维化发生中的作用,以及肝脏微循环障碍、肝窦毛细血管化与肝纤维化发生的关系. 方法对56例慢性乙型肝炎患者进行肝活组织枪查,将肝组织分成两部分,分别通过HE染色进行光学显微镜观察,以及常规制作电子显微镜标本在透射电子显微镜下进行超微结构观察.结果 56例慢性乙型肝炎患者中,轻度39例,中度10例,重度7例.慢性乙型肝炎患者肝星状细胞的形态类似成纤维细胞,周围有胶原纤维形成.窦内皮细胞与肝星状细胞间有电子致密物沉积.其中53例窦内皮细胞窗孔有不同程度的减少,减小,20例见窦内皮细胞下有连续或不连续的膜样物质形成,15例狄氏腔内有胶原纤维沉积.15例肝功能正常患者有的肝窦腔内有红细胞聚集,严重者有微血栓形成. 结论窦内皮细胞通过与肝星状细胞作用,从而参与肝纤维化的发生.肝脏微循环障碍、肝窦毛细血管化是肝纤维化的早期重要病理改变.     

从组织病理学角度探讨慢性乙型肝炎肝纤维化的发生

目的 探讨窦内皮细胞在肝纤维化发生中的作用,以及肝脏微循环障碍、肝窦毛细血管化与肝纤维化发生的关系. 方法对56例慢性乙型肝炎患者进行肝活组织枪查,将肝组织分成两部分,分别通过HE染色进行光学显微镜观察,以及常规制作电子显微镜标本在透射电子显微镜下进行超微结构观察.结果 56例慢性乙型肝炎患者中,轻度39例,中度10例,重度7例.慢性乙型肝炎患者肝星状细胞的形态类似成纤维细胞,周围有胶原纤维形成.窦内皮细胞与肝星状细胞间有电子致密物沉积.其中53例窦内皮细胞窗孔有不同程度的减少,减小,20例见窦内皮细胞下有连续或不连续的膜样物质形成,15例狄氏腔内有胶原纤维沉积.15例肝功能正常患者有的肝窦腔内有红细胞聚集,严重者有微血栓形成. 结论窦内皮细胞通过与肝星状细胞作用,从而参与肝纤维化的发生.肝脏微循环障碍、肝窦毛细血管化是肝纤维化的早期重要病理改变.     

从组织病理学角度探讨慢性乙型肝炎肝纤维化的发生

目的 探讨窦内皮细胞在肝纤维化发生中的作用,以及肝脏微循环障碍、肝窦毛细血管化与肝纤维化发生的关系. 方法对56例慢性乙型肝炎患者进行肝活组织枪查,将肝组织分成两部分,分别通过HE染色进行光学显微镜观察,以及常规制作电子显微镜标本在透射电子显微镜下进行超微结构观察.结果 56例慢性乙型肝炎患者中,轻度39例,中度10例,重度7例.慢性乙型肝炎患者肝星状细胞的形态类似成纤维细胞,周围有胶原纤维形成.窦内皮细胞与肝星状细胞间有电子致密物沉积.其中53例窦内皮细胞窗孔有不同程度的减少,减小,20例见窦内皮细胞下有连续或不连续的膜样物质形成,15例狄氏腔内有胶原纤维沉积.15例肝功能正常患者有的肝窦腔内有红细胞聚集,严重者有微血栓形成. 结论窦内皮细胞通过与肝星状细胞作用,从而参与肝纤维化的发生.肝脏微循环障碍、肝窦毛细血管化是肝纤维化的早期重要病理改变.     

慢性乙型肝炎肝脏微循环障碍发生发展机制的研究

目的探讨慢性乙型肝炎患者肝脏微循环障碍的主要分子机制。方法选择不同纤维化分期CHB穿刺肝组织和肝硬化外科活检肝组织及健康肝移植供体肝组织,应用免疫组化EliVisionTM System法,检测肝组织中COX1、COX2、AngII、AT1及α-SMA蛋白表达情况,并分析它们与肝内小血管、微血管或肝窦病理改变的关系。结果在CHB肝组织内COX1、COX2、AngII、AT1、及α-SMA在血窦壁、肝内小的门静脉分支、肝动脉分支、中央静脉及小叶下静脉壁均呈不同程度的阳性表达,随肝纤维化程度的加重其表达水平明显升高,在活动期肝硬化肝组织内上述调节分子表达最强(x2=8.8535,P=0.0120)。结论肝纤维化和肝硬化程度与COX1、COX2等指标之间存在相关性。     

肝窦病变对慢性乙型肝炎肝脏微循环障碍的影响

目的研究肝窦病变对慢性乙型肝炎肝脏微循环障碍的影响。方法采用肝窦形态体视学方法测定肝窦数目、肝窦总面积、总周长、平均直径等指标,并采用透射电镜观察肝脏微循环结构改变特点。结果慢性乙型肝炎重度患者肝窦总面积、总周长、平均直径增大(P<0.05),肝窦内皮细胞窗孔减小、基底膜形成、Disse腔胶原沉积增加(P<0.05),但肝窦数目减少(P<0.05);慢性乙型肝炎轻度和中度患者肝窦内皮细胞中WP小体检出率分别为53.5%和59.1%,而在重度患者仅为12.9%。结论肝窦病变在慢性乙型肝炎肝脏微循环障碍中起关键作用。     

Alpha-SMA expression in hepatic stellate cells and quantitative analysis of hepatic fibrosis in cirrhosis and in recurrent chronic hepatitis after liver transplantation

BACKGROUND: The alpha isotype of actin expressed by hepatic stellate cells reflects their activation to myofibroblast-like cell and has been directly related to experimental liver fibrogenesis, and indirectly to human fibrosis in chronic liver disease. AIMS: To evaluate the changes in distribution and percentage of alpha-smooth muscle actin-positive hepatic stellate cells and the correlation with the degree of the fibrosis in cirrhotic livers, as well as in patients with recurrent HCV chronic hepatitis after liver transplantation. METHODS: Human liver biopsies were divided in four groups: (1) normal livers obtained from cadaveric liver donors (n=35), (2) cirrhosis post-HBV hepatitis (n=11), (3) cirrhosis post-HCV hepatitis (n=10), and (4) post-transplant recurrent HCV chronic hepatitis (n=13). Samples were stained with anti-alpha-smooth muscle actin antibody by immunoperoxidase method and semi-quantitatively evaluated. Liver fibrosis was assessed from specimens stained with Masson's trichrome and quantified by computer image analysis. RESULTS: The percentage of alpha-smooth muscle actin-positive hepatic stellate cells was significantly higher in the HBV cirrhosis, HCV cirrhosis and post-transplant HCV recurrent hepatitis groups (36.1+/-15.2, 23.8+/-19.7 and 27.8+/-16.4%, respectively) compared to the liver donor group (2.9+/-4.0%). The alpha-smooth muscle actin-positive hepatic stellate cells to fibrous tissue ratio were significantly higher in the post-transplant recurrent HCV hepatitis group (2.36+/-1.12) compared to both the donor livers and the HCV cirrhosis groups (0.74+/-1.09 and 1.03+/-0.91, respectively). The alpha-smooth muscle actin-positive hepatic stellate cell percentage and fibrosis correlated positively in the post-transplant recurrent HCV hepatitis group and negatively in the HCV cirrhosis group. No difference in the immunohistochemical and morphometrical variables was found between the HCV cirrhosis and HBV cirrhosis groups. CONCLUSIONS: These results indirectly confirm that, in vivo, alpha-smooth muscle actin expression is a reliable marker of hepatic stellate cells activation which precedes fibrous tissue deposition even in the setting of recurrent HCV chronic hepatitis after liver transplantation, and it could be useful to identify the earliest stages of hepatic fibrosis and monitoring the efficacy of the therapy. In the presence of advanced cirrhosis other factors, rather than alpha-smooth muscle actin-positive hepatic stellate cells, may sustain fibrosis deposition.     

Hemodynamic and morphologic changes of peripheral hepatic vasculature in cirrhotic liver disease： A preliminary study using contrast-enhanced coded phase inversion harmonic ultrasonography

AIM: To provide the useful information for the diagnosis of liver cirrhosis by observing the morphology of peripheral hepatic vessels and the hemodynamics of microbubble arrival time in these vessels. METHODS: Twenty-one subjects including 5 normal volunteers and 16 patients (liver cirrhosis, n=10; chronic hepatitis, n=6) were studied by contrast-enhanced coded phase inversion harmonic sonography (GE LOGIQ 9 series) using a 6-8 MHz convex-arrayed wide-band transducer. The images of peripheral hepatic artery, portal and hepatic vein were observed in real-time for about 2 min after intravenous injection of Levovist. The time when microbubbles appeared in the peripheral vessels (microbubble arrival time) was also recorded. The morphologic changes of peripheral hepatic vasculature were classified as marked, slight, and no changes based on the regularity in caliber, course, ramification, and the delineation of vessels compared to normal subjects. RESULTS: The microbubble arrival time at peripheral artery, portal, and hepatic vein was shorter in cirrhotic patients than in chronic hepatitis patients and normal subjects. The marked, slight and no morphologic changes of peripheral hepatic vasculature found in 5 (5/6, 83.3%), 1 (1/6, 16.7%), and 0 (0/6, 0%) liver cirrhosis patients, respectively, and in 1 (1/10, 10%), 6 (6/10, 60%), and 3 (3/10, 30%) chronic hepatitis patients, respectively. There was a significant difference between the two groups (P<0.001). CONCLUSION: Evaluation of the hemodynamics and morphology of peripheral hepatic vasculature by contrast-enhanced coded pulse inversion harmonic sonography can provide useful information for the diagnosis of liver cirrhosis.     

血清透明质酸水平与肝脏微循环状况的关系

寻求一个无创伤性，且能灵敏。准确地反映肝脏微循环障碍程度的血清学指标。探讨血清透明质酸（HA）水平与肝脏微循环状况之间的关系。45例乙型肝炎患者全部行肝穿刺活检。肝穿组织分别行HE染色，免疫组化染色及电镜观察。同时用放免法检测血清HA水平，慢性乙型肝炎患者的血清HA水平均高于正常对照组。且随病变加重，HA逐渐增高，血清HA水平与肝脏微循环障碍程度，肝窦内皮细胞（SEC）损伤，肝窦毛细血管化均呈显著正相关，相关系数分别为0.390,0.435和0.451。常规肝功能检测项目与肝脏微循环障碍均无显著相关。血清HA水平可反映SEC功能，是反映肝脏微循环状况的一个良好指标。优于常规肝功能检测。     

慢性乙型肝炎时肝窦内皮细胞变化及其意义

目的：观察慢性乙型肝炎肝组织窦内皮细胞（SEC）的形态学改变，探讨其与肝脏微循环障碍的关系。方法：对53例慢性乙型肝炎患者进行肝脏活检术，肝脏活检组织分别进行光镜和电镜观察。结果：慢性肝炎患者SEC发生了很大变化，主要表现在窗孔减小、减少，SEC下基底膜形成，SEC间出现细胞连接，SEC胞质内出现WP小体及SEC脱落现象。随慢性乙型肝炎病变程度加重，SEC形态改变愈为显著。SEC与淋巴细胞、库普弗细胞之间亦发生了密切接触。结论：慢性乙型肝炎肝组织的SEC形态上发生了很大变化，这可能是肝脏微循环障碍的启动步骤。     

Impact of cirrhosis on the development of experimental hepatic metastases by B16F1 melanoma cells in C57BL/6 mice

Metastases rarely occur in human livers with cirrhosis in clinical studies. We postulated that this phenomenon would also occur in experimental cirrhosis. Cirrhosis was established in C57BL/6 mice by carbon tetrachloride (CCl(4)) gastrogavage. B16F1 melanoma cells were injected into the mesenteric vein to induce hepatic metastases. Contrary to our postulate, there was greater than 4-fold increase in metastasis in animals with cirrhosis compared to controls. Intravital videomicroscopy showed that the hepatic sinusoids were narrower and more tumor cells were retained in the terminal portal vein (TPV) in cirrhotic livers. Immunohistochemistry demonstrated that the expression of vascular adhesion molecules was significantly increased in cirrhosis. Using confocal microscopy and the fluorescent nitric oxide (NO) probe 4,5-diaminofluorescein diacetate, a significantly lower level of NO release was detected in livers with cirrhosis both in basal conditions and after tumor cell arrest. Eight hours after mesenteric vein tumor cell injection, the percentage of apoptotic tumor cells in the sinusoids was 17% +/- 2% in livers with cirrhosis and 30% +/- 5% in normal livers. More mitotic and Ki-67 labeled tumor cells were seen in livers with cirrhosis. In conclusion, the changes in architecture and adhesion molecule expression in livers with cirrhosis may cause more tumor cells to arrest in the TPV. Lower levels of NO production may reduce apoptosis of B16F1 cells in livers with cirrhosis. As a result, these changes may promote the growth of metastasis in this cirrhotic model.     

Pyridinoline collagen cross-links in patients with chronic viral hepatitis and cirrhosis

Background/Aims: The mature form of collagen cross-linking increases the resistance of collagen to degradative enzymes, and thus renders the protein in the fibrotic lesions extremely stable and the fibrosis virtually irreversible. It is crucial to elucidate the extent of cross-linking in fibrotic and cirrhotic livers if we are to control the subsequent removal of the excessive deposited collagen, whether by natural enzymes or induced by therapy. We aimed to quantitative pyridinoline, a mature form of the cross-linking, in normal control livers, viral fibrotic livers with various degrees of fibrosis and viral cirrhotic livers.Methods: Needle liver biopsy samples from 75 patients with chronic viral hepatitis and 13 patients with viral liver cirrhosis, and six normal control livers were analyzed. Collagen and pyridinoline contents were determined by high-performance liquid chromatography.Results: Significantly higher levels of pyridinoline cross-links per collagen molecule were found in the viral cirrhotic livers (0.60 [0.46, 0.65] pmol/pmol of collagen; median [25%, 75%]) compared with those in normal livers (0.39 [0.24, 0.43] pmol/pmol of collagen, p=0.03491). But no differences were found in levels between cirrhosis and chronic hepatits with various degrees of fibrosis. These data suggest that liver collagen may be susceptible to degradation to a similar degree in viral cirrhosis and in chronic viral hepatitis.Conclusion: The extent of the pyridinoline cross-linking of hepatic collagen does not seem to be responsible for the irreversibility of viral liver fibrosis.