Hepatic and portal vein thrombosis in cirrhosis: Possible role in development of parenchymal extinction and portal hypertension

Obliterative lesions in portal veins (PVs) and hepatic veins (HVs) of all sizes are known to occur in cirrhotic livers. PV lesions have generally been attributed to thrombosis, but the pathogenesis of the HV (veno-occlusive) lesions is unknown. We have studied 61 cirrhotic livers removed at transplantation to clarify the prevalence, distribution, and pathogenesis of venous lesions, as well as the association of these lesions with other morphological features and clinical morbidity. Intimal fibrosis that is highly suggestive of healed HV or PV thrombosis was found in at least 70% and 36% of livers, respectively. The distribution of HV lesions was patchy and largely confined to veins between 0.1 and 3 mm in diameter, suggesting multifocal origin in small veins. PV lesions were more uniform throughout the liver, suggesting origin in large veins with propagation to the small veins. HV lesions were associated with regions of confluent fibrosis (focal parenchymal extinction), and PV lesions were associated with regional variation in the size of cirrhotic nodules and a history of bleeding varices. These observations suggest that thrombosis of medium and large PVs and HVs is a frequent occurrence in cirrhosis, and that these events are important in causing progression of cirrhosis.     

Diffuse expression of heparan sulfate proteoglycan and connective tissue growth factor in fibrous septa with many mast cells relate to unresolving hepatic fibrosis of congenital hepatic fibrosis.

BACKGROUND AND AIMS: Congenital hepatic fibrosis (CHF) is characterized by dense portal/septal fibrosis and bile duct proliferation and tortuosity. In this study, the roles and significance of fibrosis-related cells and molecules in the process of progressive and unresolving fibrosis of CHF were examined in comparison with other fibrotic liver diseases. METHODS: Seven CHF livers were examined, and a total of 74 control livers (chronic viral hepatitis (CVH), alcoholic fibrosis/cirrhosis (F/C), extrahepatic biliary obstruction and livers showing non-specific reactive changes) were used as controls. All of these livers were wedge biopsied or surgically resected ones, and were formalin fixed and paraffin embedded. In addition to histologic observations, expression of heparan sulfate proteoglycan (HSPG), connective tissue growth factor (CTGF), mast cell-specific tryptase, alpha-smooth muscle actin for activated hepatic stellate cells (HSC) or myofibroblasts (MF) were immunohistochemically surveyed. HSPG and CTGF at mRNA were also examined by in situ hybridization. RESULTS: Portal/septal fibrosis of CHF were mature collagenous and elastic fiber poor, when compared with controls. HSPG and CTGF were diffusely abundant in fibrous portal tracts/septa in CHF, while they were more or less accentuated at periportal areas in alcoholic F/C and CVH. In CHF, the number of interface and portal/septal MF was increased from mild-to-moderate degree, while their increase was moderate to marked in alcoholic F/C and CVH, particularly F3/F4. While activated HSC were frequent in alcoholic F/C and CVH and they were continuous with interface MF, activated HSC in CHF were scanty. Instead, mast cells were increased in portal/septal fibrosis of CHF. Portal mononuclear cells and endothelial cells were positive for HSPG mRNA, and mononuclear cells for CTGF mRNA, and such cells were accentuated around proliferated bile ducts and ductules in CHF. CONCLUSIONS: Abundant CTGF retained diffusely in HSPG in the fibrous portal tracts/septa may be responsible for non-resolving hepatic fibrosis in CHF, and many mast cells and portal MF not related to HSC may causally relate to such characteristic finding in CHF.     

Significance of septal fibrosis for disturbance of hepatic circulation.

To examine the significance of fibrous septa of the liver for hepatic circulatory disturbance, haemodynamic changes were investigated in rats with septal fibrosis induced with horse serum injections. The fibrotic liver showed thin fibrous bands originating in the vicinity of the peripheral branches of the hepatic vein connected with each other and partly with the portal triads, without conspicuous periportal, pericentral or perisinusoidal fibrosis. There was no evidence of hepatic cell enlargement, disarrangement of hepatic cell plates or narrowing of the sinusoids in the fibrotic livers. Portal vascular resistance, bile production and hepatic oxygen consumption, which were measured by an isolated liver perfusion method, were much the same in the normal and the fibrotic livers. Moreover, there was no significant difference in in vivo blood pressures of the portal vein, the terminal portal venule, the terminal hepatic venule and the inferior vena cava between the normal and the fibrotic rats. These data suggest that septal fibrosis in itself does not disturb hepatic circulation.     

Significance of septal fibrosis for disturbance of hepatic circulation

Abstract: To examine the significance of fibrous septa of the liver for hepatic circulatory disturbance, haemodynamic changes were investigated in rats with septal fibrosis induced with horse serum injections. The fibrotic liver showed thin fibrous bands originating in the vicinity of the peripheral branches of the hepatic vein connected with each other and partly with the portal triads, without conspicuous periportal, pericentral or perisinusoidal fibrosis. There was no evidence of hepatic cell enlargement, disarrangement of hepatic cell plates or narrowing of the sinusoids in the fibrotic livers. Portal vascular resistance, bile production and hepatic oxygen consumption, which were measured by an isolated liver perfusion method, were much the same in the normal and the fibrotic livers. Moreover, there was no significant difference in in vivo blood pressures of the portal vein, the terminal portal venule, the terminal hepatic venule and the inferior vena cava between the normal and the fibrotic rats. These data suggest that septal fibrosis in itself does not disturb hepatic circulation.     

CD14-positive hepatic monocytes/macrophages increase in hereditary hemochromatosis.

BACKGROUND/AIMS: Iron overload in hereditary hemochromatosis (HH) may result in hepatic fibrosis and cirrhosis, primarily due to collagen production by hepatic stellate cells that become activated to myofibroblasts. Endotoxin-responsive monocytes/macrophages (CD14-positive) are potential sources of profibrogenic factors. The aims of this study were to determine (1) whether CD14-positive monocytes/macrophages are present in the livers of patients with HH and (2) the potential relationship between CD14-positive cells and hepatic fibrosis in HH. METHODS: HH was diagnosed using standard clinical, biochemical and genotypic parameters. Liver specimens from HH patients and control subjects were immunostained for CD14, CD68 and alpha-smooth muscle actin (alpha-SMA) and the number of cells expressing these antigens was determined. Fibrosis was assessed by routine histological methods. RESULTS: The total number of hepatic CD68-positive monocytes/macrophages was similar in HH patients and control subjects; however, there was a nine-fold increase in the number of CD14-positive monocytes/macrophages in HH patients. Control subjects had very low levels of hepatic CD14 expression. In HH livers with advanced fibrosis, CD14-positive monocytes/macrophages were often associated with fibrous septa containing myofibroblasts expressing alpha-SMA. CONCLUSIONS: There was a substantial increase in hepatic CD14-positive monocytes/macrophages in HH and, in livers with advanced fibrosis, these cells were often associated with fibrous septa and septal myofibroblasts. The total number of monocytes/macrophages was similar in HH and control livers. In control human liver, Kupffer cells had a very low expression of CD14. These findings suggest that CD14-positive monocytes/macrophages may contribute to the process of hepatic fibrogenesis in HH.     

特发性门脉高压症的临床病理学特点

目的 探讨特发性门脉高压症(idiopathic portal hypertension,IPH)的临床病理学特点.方法 回顾性分析了9例IPH的临床及病理学资料,并对其肝脏标本进行常规病理学及免疫组化研究.结果 9例IPH中,5例首发症状为上消化道出血和黑便,3例体检发现脾大脾亢而无临床症状,1例以血管瘤入院.人院检查脾肿大7例,胃底食道静脉曲张6例,腹水征4例,贫血者6例,肝功能正常或接近正常9例.病理组织学显示9例肝小叶结构基本正常.均未见假小叶形成及肝细胞坏死;9例均有不同程度汇管区纤维化,3例汇管区纤细的不全纤维间隔形成并向肝实质延伸,6例有门脉末支管壁纤维化;9例中有6例小叶内肝细胞有不同程度的水肿变性,5例肝窦有不同程度的扩张,2例肝窦扩张较明显,肝细胞萎缩,呈血管瘤样结构,2例有轻-中度肝腺胞3区大泡脂变.脾脏组织学符合淤血性脾肿大病理表现.结论 IPH的临床表现与其他原因所致的肝硬化门脉高压相似,肝穿组织病理学可除外肝硬化,并有一定的特征.诊断时应与各种原因所致肝硬化门脉高压,肝窦阻塞综合征等相鉴别.     

Expression of angiotensin II type 1 receptor in human cirrhotic livers: Its relation to fibrosis and portal hypertension.

Angiotensin II (ANG-II) and its receptor (AT1) have been potential targets of therapy for liver cirrhosis. However, AT1 expression in human cirrhotic livers has not been clarified. We studied AT1 and ANG-II generating enzymes in human autopsy (20 cirrhotics and 20 normal controls) and biopsy (10 cirrhotics) livers. AT1 immunoreactivity in tissue sections was quantified by computer-aided morphometry. AT1 protein and mRNA levels were assessed by Western blotting and real-time polymerase chain reaction. Concerning ANG-II generating system, angiotensin-converting enzyme (ACE) and mast cell chymase were examined. AT1 expression was seen not only in vascular smooth muscle cells, but also in activated stellate cells/myofibroblasts and liver parenchymal cells. AT1-positive vessels and myofibroblasts were significantly increased in fibrous septa of cirrhosis, although overall hepatic AT1 expression was reduced in the cirrhotic livers compared with the controls. Augmentation of AT1-positive vessels was related to severity of portal hypertension. Expressions of ACE and chymase were enhanced in the cirrhotic livers. These results suggest that hepatic AT1 expression is shifted to and concentrated in vessels and myofibroblasts in cirrhotic settings, and increased ANG-II generation by ACE and chymase contributes to portal hypertension and liver fibrosis via binding to AT1 expressed on vessels and myofibroblasts.     

慢性乙型肝炎肝窦及窦周隙的病变与肝纤维化的关系

目的 探讨慢性乙型肝炎肝窦及窦周隙内病变及其与肝纤维化的关系。方法 采用ＨＥ。特殊染色及免疫组织化学染色法,用光镜观察肝组织病理分级诊断为Ｇ１－Ｇ４和活动性肝硬化（ＡＬＣ）各３０例,慢性重型肝炎（ＣＳＨ）１０例的肝活检组织中各成分的分布。设正常肝５例和肝硬化（ＬＣ）１０例作对照,结果 肝窦及窦周隙病理改变有塌陷、扩张、阻塞及狭窄、平滑肌肌动蛋白分布演变尤具特征性。ＣＩＶ、ＦＮ和ＬＮ三种成分在肝窦沉     

Spatial distribution of tissue inhibitor of metalloproteinase-1 mRNA in chronic liver disease

BACKGROUND/AIMS: Tissue inhibitor of metalloproteinase-1, a specific inhibitor of matrix metalloproteinases, plays an important role in the pathogenesis of fibrosis and tumor progression. However, the precise expression of tissue inhibitor of metalloproteinase-1 messenger RNA in human hepatic fibrosis has not yet been defined. We investigated the spatial distribution of tissue inhibitor of metalloproteinase-1 messenger RNA in chronic human liver disease. METHODS: Northern and in situ hybridization of probes to tissue inhibitor of metalloproteinase-1 messenger RNA were performed in specimens from 16 surgically resected human livers. Immunohistochemical staining of sections for tissue inhibitor of metalloproteinase-1 and immunoelectron microscopy were also performed. RESULTS: Northern hybridization demonstrated that expression of tissue inhibitor of metalloproteinase-1 messenger RNA was increased 3.9-fold in mild chronic hepatitis, 6.8-fold in moderate chronic hepatitis, and 6.4-fold in cirrhosis, compared with control liver. In situ hybridization showed the expression of tissue inhibitor of metalloproteinase-1 messenger RNA in spindle-shaped cells in the fibrous septa and lobules in chronic hepatitis and cirrhosis; these cells were immunohistochemically positive for a-smooth muscle actin. Immunoelectron microscopy revealed localization of tissue inhibitor of metalloproteinase-1 in between fibers, to the rough endoplasmic reticula of stellate cells located in the lobules and periportal areas, and to fibroblasts in the fibrous septa. These results indicate that tissue inhibitor of metalloproteinase-1 was produced mainly by stellate cells in the specimens of chronic liver diseases. CONCLUSIONS: Expression of tissue inhibitor of metalloproteinase-1 messenger RNA is increased in hepatic fibrosis and stellate cells are involved primarily in its expression.     

Differential findings for CD14-positive hepatic monocytes/macrophages in primary biliary cirrhosis, chronic hepatitis C and nonalcoholic steatohepatitis.

BACKGROUND AND AIMS: Endotoxin-responsive monocytes/macrophages (CD14-positive) are potential sources of profibrogenic factors. The aims of this study were to determine (1) whether hepatic CD14-positive cells are present in various forms of chronic liver disease, and (2) the relationship between CD14-positive cells, myofibroblasts, and fibrosis in these diseases. METHODS: Liver specimens from control subjects (n = 12) and those with primary biliary cirrhosis (n = 18), chronic hepatitis C (n = 13), or nonalcoholic steatohepatitis (n = 13) were immunostained for CD14, CD68, and alpha-smooth muscle actin (SMA) and the number of cells expressing these antigens was determined. Fibrosis and inflammation were also assessed. RESULTS: The total number of hepatic CD68-positive cells was similar in diseased and control livers. The number of CD14-positive cells was increased in advanced fibrosis in primary biliary cirrhosis and hepatitis C but not in nonalcoholic steatohepatitis. The number of CD14-positive cells was also increased in hepatitis C specimens with high inflammatory activity. CD14-positive cells were often associated with alpha-SMA-positive myofibroblasts in fibrous septa. CONCLUSIONS: The number of hepatic CD14-positive cells is increased in advanced fibrosis in subjects with primary biliary cirrhosis and hepatitis C but not in nonalcoholic steatohepatitis. In primary biliary cirrhosis and hepatitis C, CD14-positive macrophages are found in close proximity to fibrous septa and myofibroblasts. In hepatitis C, an increased number of CD14-positive cells are associated with high inflammatory activity.     

Incomplete septal cirrhosis associated with Wegener's granulomatosis

Incomplete septal cirrhosis, which is included in the spectrum of hepatoportal sclerosis, is characterized by parenchymal nodularity, incomplete fibrous septa, clustered or dispersed portal tract remnants, and abnormal spacing of portal tracts and hepatic veins. Hepatoportal sclerosis is known to be associated with collagen vascular diseases. Here, we describe a 73 year-old-female with incomplete septal cirrhosis. At 57 years, she presented with respiratory symptoms, and lung biopsy disclosed active arteritis with granuloma. Perinuclear antineutrophilic cytoplasmic antibody was also positive. Immunosuppressive therapy was done under the diagnosis of Wegener's granulomatosis. At 63 years, liver dysfunction was noted, and laparoscopy revealed uneven surface of the liver and dilatation of the umbilical vein. Liver dysfunction progressed, and she developed encephalopathy and massive ascites. She died of sepsis at 73 years. At autopsy the liver (700 g) was macronodular with several deep depressions. The parenchyma showed fine and diffuse nodularity. Grossly visible portal and hepatic veins were patent. The above-mentioned histologic features characterizing incomplete septal cirrhosis were found. This is the first report of incomplete septal cirrhosis associated with Wegener's granulomatosis implying that vascular and extravascular lesions of Wegener's granulomatosis might have been related to the pathogenesis of incomplete septal cirrhosis.     

Hepatic content of collagens and laminin in rat model of experimental liverfibrosis

AIM The hepatic content of collagens (type I, Ⅲ and Ⅶ) and laminin (LN) in rat model of experimentalliver fibrosis was observed to find out their roles in the pathogenesis of liver fibrosis.METHODS The experimental rat model was established by immunological injury induced by injectinghuman albumin. Histopathological and immunohistochemical methods were used to measure the hepaticcontent of collagens and laminin in the fibrotic rat livers.RESULTS The hepatic contents of collagens (type I, Ⅲ, Ⅶ) and LN in the fibrotic rat livers weresignificantly increased as compared with those in the control group, and they were found to be mainlylocalized in the portal space, central veins and fibrous septa. Electron microscopic study showed that pro-collagens were present around the “activated” hepatic stellate cells (HSC) and the hepatocytes atrophied.CONCLUSION Pathological deposition of collagens (type Ⅰ, Ⅲ and Ⅶ ) and laminin was the fundamentallesion of liver fibrosis. HSC may be the major cellular source of collagens (type Ⅰ, Ⅲ and Ⅶ) and laminin inthe liver tissue.     

Multiple macroregenerative nodules in liver cirrhosis due to Budd-Chiari syndrome. Case reports and review of the literature

Clinical, radiological, histological and immunohistochemical methods were used to define the nature of multiple rapidly growing hepatic nodules in 2 young patients with Budd-Chiari syndrome due to myeloproliferative diseases. In one patient, the arterial hyperperfusion of large nodules was demonstrated by dynamic computed tomography and angiography. The explanted livers of these patients showed multiple well-demarcated nodules up to 3 cm in diameter on the background of liver cirrhosis resulting from chronic hepatic congestion. Histologically, these nodules covered a spectrum ranging from adenoma-like lesions to nodules resembling focal nodular hyperplasia. They consisted of essentially normal hepatocytes, and variably contained fibrous septa including neoductules and large, mostly dysmorphic arteries. Sometimes, they were located close to still patent or recanalized veins. These rapidly growing hepatic nodules are best defined as macroregenerative nodules. The knowledge of this entity may help the physician to avoid misinterpretation of such nodules as carcinomas.     

Role of septal fibrosis in development of hepatic circulatory disturbance in the presence of liver cell enlargement

Abstract: The effect of septal fibrosis on hepatic circulation was examined in rats with enlarged liver cells. Septal fibrosis was produced by horse serum injections and liver cell enlargement by a choline-deficient diet. Septal fibrosis alone did not induce any disturbance of hepatic circulation. In fatty livers, a slight increase in sinusoidal vascular resistance and a slight elevation of portal vein pressure were found. However, in fatty livers with septal fibrosis, portal hypertension and sinusoidal vascular resistance were higher than in fatty livers without septal fibrosis. These experimental data clearly demonstrate that septal fibrosis alone has no effect on hepatic circulation, but septal fibrosis in the presence of liver cell enlargement markedly affects sinusoidal circulation and induces portal hypertension. The augmentation of sinusoidal vascular resistance by septal fibrosis in the presence of liver cell enlargement might be due to the severe deformation of the sinusoids by enlarged liver cells in the limited spaces surrounded by septal fibrous bands.     

Role of septal fibrosis in development of hepatic circulatory disturbance in the presence of liver cell enlargement.

The effect of septal fibrosis on hepatic circulation was examined in rats with enlarged liver cells. Septal fibrosis was produced by horse serum injections and liver cell enlargement by a choline-deficient diet. Septal fibrosis alone did not induce any disturbance of hepatic circulation. In fatty livers, a slight increase in sinusoidal vascular resistance and a slight elevation of portal vein pressure were found. However, in fatty livers with septal fibrosis, portal hypertension and sinusoidal vascular resistance were higher than in fatty livers without septal fibrosis. These experimental data clearly demonstrate that septal fibrosis alone has no effect on hepatic circulation, but septal fibrosis in the presence of liver cell enlargement markedly affects sinusoidal circulation and induces portal hypertension. The augmentation of sinusoidal vascular resistance by septal fibrosis in the presence of liver cell enlargement might be due to the severe deformation of the sinusoids by enlarged liver cells in the limited spaces surrounded by septal fibrous bands.     

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.     

Genetic and acquired thrombotic factors in chronic hepatitis C

OBJECTIVES: During the progression of chronic liver disease towards cirrhosis, morphological studies have shown a close association between parenchymal remodeling and obliterative lesions of intrahepatic small portal and hepatic veins. These lesions are highly suggestive of intrahepatic thrombotic events, which may have a key role in the pathogenesis of hepatic fibrosis. The aim of the study was to investigate thrombotic risk factors in chronic hepatitis C patients with different extent of liver fibrosis. METHODS: The following thrombotic factors were evaluated in 68 hepatitis C patients with prothrombin activity >/= 80% (34 consecutive patients with extensive fibrosis and/or cirrhosis compared with 34 consecutive patients without extensive fibrosis and/or cirrhosis): factor V Leiden, G20210A prothrombin mutation, antithrombin, protein C and S deficiencies, hyperhomocysteinemia, elevated factor VIII level, and lupus anticoagulant. RESULTS: Three thrombotic risk factors were significantly more frequent in patients with extensive fibrosis and/or cirrhosis than in those without extensive fibrosis: protein C deficiency present in 14 patients (41%) as compared with three patients (9%), p= 0.004; elevated factor VIII level present in 19 patients (56%) as compared with six patients (18%), p= 0.002; and hyperhomocysteinemia present in 10 patients (29%) as compared with two patients (6%), p= 0.023. The association of two or three prothrombotic factors was present in 19 patients (56%) with extensive fibrosis and/or cirrhosis as compared with one patient (3%) without extensive fibrosis and/or cirrhosis, p < 0.001. CONCLUSION: Multiple thrombotic risk factors coexist frequently in patients with extensive fibrosis and early stage of cirrhosis. Their association with local inflammation could favor thrombotic events in the liver micro-circulatory bed.     

明胶酶原A在实验性肝纤维化过程中表达变化

目的研究实验性肝纤维化过程中明胶酶A(mmp-2)酶原蛋白表达的动态变化.方法建立四氯化碳大鼠肝纤维化模型,采用Western印迹法和免疫组化方法,对肝纤维化不同阶段肝内mmp-2的酶原蛋白的表达水平与分布进行了检测.结果在正常大鼠肝组织中有mmp-2的酶原表达.在肝纤维化发生发展过程中mmp-2酶原蛋白表达水平逐渐增强,至肝纤维化中期到达最高峰,到肝纤维化晚期及肝硬变阶段其表达较中期下降,但仍高于正常对照水平.正常肝组织内,mmp-2的表达主要位于汇管区的胆管壁和毛细血管壁及肝窦壁的间质细胞;纤维化时,增生的纤维间隔附近亦有较高表达.结论 mmp-2在肝纤维化的发生、发展直至肝硬变形成过程中发挥着重要作用.     

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,无狭窄和闭塞,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。     

实验性肝纤维化时肝内纤维及血管的三维结构 观察及复方中药对其影响

目的 观察实验性肝纤维化时肝内纤维及血管的三维结构改变以及复方861治疗对其影响。方法 应用人血白蛋白制造免疫损伤性大鼠肝纤维化模型,采用肝组织连续切片电子计算机辅助病理组织三维重建技术,对肝纤维化以及复方861治疗后肝组织的纤维间隔及肝血窦等结构进行三维观察及体积测量。结果 肝纤维化时,肝内纤维沉积,肝血窦结构紊乱。复方861治疗可使纤维降解;肝血窦改建恢复,肝小叶结构趋于正常。结论 病理组织三维重建研究表明,复方861可以阻断及逆转实验性肝纤维化。