慢性肝炎肝组织内血管病变与肝纤维化及肝硬化的关系

目的研究慢性肝炎肝组织中血管病变与肝纤维化及肝硬化的关系。方法1047例慢性乙型肝炎肝活检标本，连续切片分别作HE及网状、胶原、弹力纤维组化染色，光镜观察肝组织病理分级及其中血管炎症、增生、破坏及阻塞四种病理改变与肝组织纤维化程度（分期）的关系。结果①分期与分级相关，炎症、坏死较重者（分级较高）其纤维化程度（分期）亦较高（P＜0．005）。②血管病变与肝组织的炎症、坏死及纤维化相关，即血管病变较重者肝组织分级和分期亦较高（P＜0．05）。③重度血管破坏及阻塞只见于S3及s4组，但前者在这两组分布无差异，而后者以S4（肝硬化）组较多（P＜0.05）。结论①慢性肝炎肝组织血管病变与肝组织病理学的炎症、坏死和纤维化相伴发生。③重度血管阻塞可能是肝硬化的重要原因之一。     

慢性乙型肝炎病毒感染者疾病进展中Th17细胞的变化及意义

目的:研究在慢性乙型肝炎病毒(HBV)感染者血浆和肝组织中IL-17的表达情况,并探讨Th17细胞在疾病进展中作用及临床意义。方法:研究对象为195例慢性HBV感染者(其中轻中度慢性肝炎64例,重度慢性肝炎42例,肝硬化41例,肝肿瘤48例)和40例健康对照者。采用酶联免疫吸附实验(ELISA)检测各组血浆IL-17水平,流式细胞术检测Th17细胞(CD3+CD4+IL-17A+)百分数,免疫组织化学染色(IHC)检测肝脏组织IL-17表达情况。结果:慢性肝炎重度组(12.52±4.28)、肝硬化组(8.84±3.71)血浆IL-17水平(pg/mL)明显高于慢性肝炎轻中度组(5.81±1.71)、肝肿瘤组(5.58±2.17)和对照组(5.27±1.73)(P<0.05),其中慢性肝炎重度组明显高于肝硬化组(P<0.01);慢性肝炎轻中度组(4.13±1.65)、慢性肝炎重度组(5.73±1.56)、肝硬化组(4.42±1.73)和肝肿瘤组(4.07±1.53)Th17细胞百分比明显高于对照组(2.80±0.98),其中慢性肝炎重度组明显高于其他3病例组(P<0.01)。免疫组化染色显示,慢性肝炎轻中度组和肝硬化组IL-17呈弱阳性表达,慢性肝炎重度组IL-17呈强阳性表达,而对照组和肝肿瘤患者肝组织未见IL-17表达。195例慢性HBV感染者血浆IL-17水平和与Th17细胞百分比与ALT呈正相关(tau b=0.254和tau b=0.280,P<0.01),二者与HBV DNA间无明显相关性。结论:慢性HBV感染者与Th17细胞百分比与肝脏炎症程度密切相关,Th17细胞检测可能作为一个有效的辅助指标来评价肝脏炎症程度,与疾病进展密切相关。     

1052例肝炎肝内血管病变的形态观察

通过对１０５２例肝炎肝组织的ＨＥ，组织化学及免疫组织化学染色观察，发现其肝内血管有炎症，破坏，增生及阻塞四种病变，并制定了评级标准，结果表明；（１）急，慢性肝炎皆有血管炎症，破坏及阻塞病变，其随肝病变加重而上升（Ｐ〈０．００１）；（２）血管增生可导致弹力纤维及ＦＮ增多而引起肝硬化；（３）ＡＳＨ，ＳＳＨ及ＣＳＨ肝内血管明显破坏及阻塞而导致肝梗塞，预后不良，这些发现为肝炎病理机制的研究提供了形态学依据     

388例慢性HBV感染者血清学与肝组织病理学指标的相关性分析

分析388例慢性HBV感染血清学及肝组织病理学指标的相关性.结果发现,HBeAg阳性者肝组织炎症分级为G2、G3-G4及纤维化分级为S2、S3～s4所占比率较阴性者低;纤维化分级为SO、炎症分级为GO～G1者的HBV-DNA均值显著高于纤维化分级S1～S4、炎症分级G2～G4者(P＜0.05、0.01);肝组织HBsAg表达为"+"者与"++～+++"者的血清HBV-DNA均值无显著差异;肝组织HBcAg阳性者HBV-DNA均值显著高于阴性者(P＜0.01);血清ALT水平正常及轻度升高者肝组织纤维化和(或)明显炎症发生率显著低于ALT中、重度升高者(P＜0.05).认为血清HBV-DNA与肝组织HBcAg表达有一致性,与肝内HbsAg表达无明显相关,HBV.DNA水平低可能提示肝组织炎症活动度和纤维化程度高;对慢性乙肝病毒携带者行肝活检可判断肝组织病变程度并决定是否行抗病毒治疗.     

肝内血管病变与肝炎病变关系的研究

目的　研究肝血管病变与肝损伤的关系．方法　肝病变标本２０００ 例，用ＨＥ、免疫组化及电镜技术进行研究．结果　在急性肝炎肝血管炎症、破坏及阻塞随肝坏死加重而上升（ Ｐ＜ ０－０１） ；在慢性肝炎肝血管炎症、破坏、阻塞及增生随肝病变的轻重程度而示梯度变化（ Ｐ＜ ０－０１） ；在肝硬变肝血管增生及纤维化最明显，与结节大小及纤维带宽窄相关（ Ｐ＜ ０－０１） ，伴弹力纤维化． 免疫组化示纤维带、血管内皮细胞及成肌纤维细胞αＳＭＡ 强阳性； 电镜示血管内皮细胞出芽并形成管状结构．结论　肝血管病变在各型肝病变中担当一关键角色     

肝组织病理学检查在婴儿胆汁淤积症鉴别诊断中的价值

目的:对比胆道闭锁与淤胆性婴儿肝炎的肝组织病理学的异同点,探讨肝组织病理学检查在鉴别诊断中的实际应用价值.方法:将我院2002-04/2009-12经病理诊断的胆道闭锁65例与淤胆性婴儿肝炎病例24例进行回顾性分析.结果:胆道闭锁与淤胆性婴儿肝炎肝组织病理学均可表现为肝小叶结构变化、肝细胞变性坏死、汇管区炎症、胆汁淤积、汇管区纤维化、胆管增生、巨细胞样变和髓外造血.其中胆道闭锁以汇管区纤维化、胆管增生及汇管区炎症最常见(P<0.05),而淤胆性婴儿肝炎则以巨细胞样变及髓外造血最常见(P<0.05).结论:胆道闭锁与淤胆性婴儿肝炎肝组织病理学各有特点,但有一定的重叠性.在诊断时仍需结合临床,必要时行剖腹探查.     

慢性肝炎血清总胆汁酸水平与肝组织炎症程度的关系

为了解血清总胆汁酸 (TBA)水平与肝实质病变的关系。对 10 2例慢性肝炎患者作肝活检 ,观察肝组织分级纤维化分期 ,并检测血清TBA、常规肝功白蛋白 (Alb)、总胆红素 (TBil)、谷丙转氨酶 (ALT)。肝组织炎症轻度(G1-2 ,S0 -2 )、中度 (G3 ,S1-3 )、重度 (G4S4)的TBA水平 (x±s)分别在 (16 74± 13 34) μmol/L、(72 2 5± 6 8 4 9)μmol/L和 (186 34± 96 18) μmol/L ,呈重度 >中度 >轻度状态。轻度组与中度组及中度与重度组比较均为P <0 0 1。慢性肝炎血清TBA水平与肝组织炎症程度具有良好正比关系。对估计肝实质病变程度具有重要临床价值。     

肝纤维化血清学指标诊断价值的验证研究

目的研究血清肝纤维化指标透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、IV型胶原(IVC)及层粘连蛋白(LN)与肝纤维化程度的关系,验证其在肝病不同阶段的诊断价值。方法用放射免疫法测定267例慢性肝炎患者血清HA、PCⅢ、IVC及LN水平,同时做肝组织活检,对肝组织进行炎症分级和纤维化分期,分析上述血清学指标水平与肝组织分级和分期之间的关系。结果上述指标水平与慢性肝炎发展的阶段一致,与肝组织炎症坏死和纤维化程度均呈正相关。结论血清HA、LN、PCⅢ、IVC可以做为反映肝纤维化程度的指标;联合检测有助于肝纤维化的诊断。     

血清补体C3和C4对慢性乙型肝炎患者肝组织病理状态的预测价值

目的探讨血清补体C3和C4对慢性乙型肝炎患者肝组织病理学分级和分期的预测价值。方法对220例慢性乙型肝炎患者进行肝组织病理学分级和分期,同时测定其血清补体C3和C4水平,进行相关的统计分析。结果血清补体C3和C4与肝组织病理学分级和分期之间呈显著负相关;C3和C4在肝组织不同病理学分级和分期之间差异均有统计学意义,但在相邻的肝组织病理学分级和分期之间进行两两比较时,只有补体C3在S1与S2之间比较差异有统计学意义(P=0.024),补体C4在G3与G4之间比较差异有统计学意义(P=0.016);用ROC曲线分析补体C3、C4对肝组织不同炎症活动度和纤维化程度的预测价值时,其预测效能多表现为低度(ROC曲线下面积<0.70),只有C3、C4对于重度炎症的预测效能达到了高度(ROC曲线下面积0.939)和中度(ROC曲线下面积0.859)。结论血清补体C3和C4分别对慢性乙型肝炎肝组织重度炎症有一定的预测价值,但尚不能作为预测肝组织不同病理学状态的可靠指标。     

慢性乙型肝炎肝内血管病变组织学观察

目的：观察慢性乙型肝炎(乙肝)肝内血管病变在病理发生和发展中的作有。方法：用旺、组织化学及免疫组织化学及光镜技术，对104例乙肝患者首、末2次肝活检标本作了研究。结果：肝内血管病变有血管炎症、破坏、阻塞、增生及肝窦毛细血管化表现，是乙肝的一大组织病理学特征．与其肝实质变性坏死、肝纤维化、肝硬变及预后密切相关。结论：肝内血管病变在乙肝的病理发生和发展中可能有重要作用。故在治疗中及时有效地改善其肝脏血供障碍，是亟待研究解决的课题。     

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     

乙型肝炎肝组织细胞间粘附分子-1表达

目的探讨乙型肝炎患者肝组织细胞间粘附分子－１（ｉｎｔｅｒｃｅｌｕｌａｒａｄｈｅｓｉｏｎｍｏｌｅｃｕｌｅ－１，ＩＣＡＭ－１）抗原的表达状况及其作用。方法用免疫组织化学技术检测１１例正常人和６０例乙型肝炎患者肝组织内ＩＣＡＭ－１表达情况。结果正常人和慢性无症状ＨＢｓＡｇ携带者肝细胞无ＩＣＡＭ－１表达，慢性乙型肝炎和重型肝炎患者肝细胞膜ＩＣＡＭ－１表达明显增强；肝损害越严重、坏死越明显者，其肝细胞ＩＣＡＭ－１表达越强。结论肝组织内ＩＣＡＭ－１表达在慢性乙型肝炎和重型肝炎肝坏死中起重要作用，ＩＣＡＭ－１表达水平能较好反映患者肝损害和肝组织炎症坏死程度。     

Clinical significance of liver biopsy in chronic hepatitis B patients with persistently normal transaminase

OBJECTIVE: The aim of this study was to study the clinical significance of liver biopsy for individuals who had chronic hepatitis B virus infection and persistently normal serum transaminases for more than 6 months. METHODS: A total of 452 patients with positive hepatitis B surface antigen for over 6 months underwent percutaneous liver biopsy. All liver biopsy specimens were assessed by experienced liver pathologists blinded to the liver biochemistry, and were scored according to the modified criteria of grade and stage of chronic hepatitis. Patients were divided into four groups: group A and group C patients had normal transaminases, and were hepatitis B e antigen (HBeAg) positive and HBeAg negative, respectively; group B and group D patients had elevated transaminases, and were HBeAg positive and HBeAg negative, respectively. RESULTS: All patients had necrosis and inflammation in the liver. Patients with increased serum transaminases had a significantly higher grade (G) of hepatic necrosis and inflammation and more severe (S) fibrosis compared with patients with normal transaminases (P < 0.05). However, in the latter patients, G3 was seen in 10 (5.5%) and 13 cases (9.1%), S3 in seven (3.8%) and 16 cases (11.1%), and S4 in three (1.6%) and seven cases (4.9%) in Group A and Group C, respectively. Moreover, in patients with normal transaminases, the HBeAg‐negative group had more severe fibrosis than the HBeAg‐positive group (P < 0.05). CONCLUSION: Although more severe pathological changes were more frequent in patients with elevated transaminases, significant hepatic pathology could still be found in cases with persistently normal transaminases. Liver biopsy in cases of chronic hepatitis B virus infection is helpful to accurately assess both the activity of the disease and the degree of fibrosis, and to estimate if antiviral therapy is justifiable. Patients with normal transaminases and serious hepatic necrosis, inflammation and fibrosis need proper management.     

Influence of liver fibrosis on hepatic artery Doppler resistance index in chronic hepatitis of viral origin.

BACKGROUND: Hepatic arterial Doppler sonography is increasingly being used in liver diagnostics. The determinants of the elevation of hepatic artery impedance indexes in chronic liver disease, however, have still not been fully clarified. The aim of the present study was to investigate the relationship between histological alterations and liver circulation in chronic hepatitis. METHODS: Hepatic artery resistance index and portal flow velocity were measured using Doppler sonography in 47 patients with chronic hepatitis of viral origin diagnosed at histopathology. The patients were divided into two groups, those with mild and those with severe alterations, in accordance with the various histological parameters of the Knodell scoring system. RESULTS: Hepatic artery resistance index and age were higher in patients with more severe liver fibrosis (respectively 0.638 +/- 0.084 and 39.0 +/- 10.9 (years) in mild fibrosis versus 0.687 +/- 0.060 and 49.4 +/- 14.4 (years) in severe fibrosis; P < 0.05 for both), whereas no difference between the two groups was found for the other histological features (degeneration, inflammation and necrosis), nor for portal flow velocity. CONCLUSIONS: The increase in hepatic artery resistance index appears to be influenced by the extent of fibrous tissue deposition in the liver, determined by chronic inflammation and repair and, secondly, by ageing.     

Hepatitis C viral infection in liver transplant recipients.

In this study we examined multiple serial liver biopsy specimens from liver transplant recipients to determine the pathological features of hepatitis C virus-induced hepatitis. Hepatitis C virus infections acquired after transplantation and previous infections that recurred in patients after transplantation were confirmed by the results of the polymerase chain reaction. Of 43 patients infected with the hepatitis C virus, 18 had a mild form of chronic hepatitis. Four patients had hepatitis that progressed to focal bridging fibrosis or cirrhosis. There were no significant clinical or pathological differences between infections acquired after transplantation and recurrent infections (as determined by polymerase chain reaction) except that acquired infections more often developed into hepatitis. Findings indicative of hepatitis C infection included portal and parenchymal mononuclear infiltrates of varying degrees, acidophilic necrosis and swollen hepatocytes. Other common findings included lymphoid aggregates, bile duct damage and fatty change. Atypical pathological conditions included extensive hepatocyte swelling or acidophilic necrosis with minimal inflammation mimicking ischemia and ductal or ductular damage and proliferation with mixed portal infiltrates mimicking rejection or obstruction. We conclude that in transplant recipients infection by the hepatitis C virus usually produces a mild disease state, but the diagnosis of hepatitis can be difficult to make because indicators of hepatitis may mimic those of rejection, ischemia, obstruction or other hepatic infections. Serial biopsy specimens with persistent pathology and polymerase chain reaction may be necessary to define the presence of a hepatitis C virus lesion.     

Serum procollagen-III-peptide: Failure to reflect the extent of hepatic fibrosis

Abstract In order to test the hypothesis that serum levels of the amino terminal propeptide of type III procollagen (PPCP III) reflect hepatic fibrosis, we have studied PPCP III levels in 30 patients with genetic haemochromatosis (GH), a disease which is characterized by progressive fibrosis without significant inflammation or necrosis. Patients with alcoholic liver disease and chronic hepatitis were included as comparative diseases in which fibrosis occurs concurrently with inflammation and necrosis. Of 13 GH cases with cirrhosis, four (30%) had normal serum PPCP III levels, while of 17 GH cases without cirrhosis, two (12%) had elevated levels. The mean serum concentrations of the cirrhotic and non-cirrhotic GH groups were not significantly different when patients with excessive alcohol consumption (> 80 g/day) were excluded from the GH groups. In 29 subjects with alcoholic liver disease, serum PPCP III correlated significantly with both fibrosis ( P < 0.01) and necrosis ( P < 0.02) but not with inflammation. In 23 subjects with chronic hepatitis, PPCP III levels correlated significantly with inflammation when assessed histologically ( P < 0.01) or as reflected by serum AST ( P < 0.01), but not with fibrosis or necrosis. Furthermore, the correlation between PPCP III and inflammation was not strengthened when the three features (inflammation, necrosis and fibrosis) were combined into a single variable. We conclude that elevated PPCP III levels in chronic liver disease do not reflect solely the extent of fibrosis but are also influenced by inflammation and necrosis and are thus of limited clinical value in predicting hepatic histopathology.     

免疫清除期相同肝实质细胞体积分摊的血清HBV DNA载量与肝组织炎症分级的关系

目的 阐明慢性乙型肝炎自然病程中免疫清除期相同肝实质细胞体积分摊的血清HBVDNA载量水平与肝组织炎症分级的关系. 方法 使用荧光多聚酶链反应分别检测和比较慢性乙型肝炎免疫清除期患者肝组织病理炎症分级1、2、3、4级的血清HBV DNA载量,以及肝组织炎症分级1、2,3、4级所在肝纤维化分期用相同肝实质细胞体积分摊的血清HBV DNA载量.多组资料两两比较采用ANOVA检验分析. 结果 176例处于免疫清除期慢性乙型肝炎患者肝组织病理学炎症分级1、2、3、4级血清HBV DNA载量分别为(8.20×10~5±9.11×10~1)拷贝/ml、(16×10~6±5.96×10~1)拷贝/ml、(8.12×10~5±8.01×10~1)拷贝/ml和(2.08×10~6±3.69×10~1)拷贝/ml,差异无统计学意义(P>0.05).然而,肝组织病理炎症1、2、3、4级所在肝纤维化分期用相同肝脏实质细胞体积分摊后的血清HBV DNA载量分别为(9.24×10~8±9.35×10~2)拷贝/ml、(5.33×10~9±7.56×10~2)拷贝/ml、(1.06×10~(10)±1.77×10~3)拷贝/ml、(3.31×10~(11)± 5.18×10~2)拷贝/ml,差异有统计学意义(P<0.05).结论 在HBV感染的自然病程中,从免疫耐受期进入免疫清除期后,肝细胞反复出现炎症,坏死,同时伴纤维组织增生.不同肝纤维化分期中相同肝实质细胞体积分摊的血清HBV DNA载量水平与肝组织炎症分级有关.     

Upregulation of lymphotoxin beta expression in liver progenitor (oval) cells in chronic hepatitis C

BACKGROUND: Bipotent liver progenitor (oval) cells with the ability to differentiate into hepatocytes and biliary epithelium have recently been identified in human subjects with hepatitis C. Animal studies suggest that members of the tumour necrosis factor family, including lymphotoxin beta (LT-beta), regulate oval cell proliferation in liver disease, but its role in human liver disease is unclear. AIMS: This study seeks to establish a role for LT-beta in hepatitis C related liver injury and to provide evidence that its increased expression is related to the presence of oval cells. METHODS: Liver biopsy specimens were obtained from patients with chronic hepatitis C virus (HCV) infection (n=20). Control liver samples (n=5) were obtained from liver resection or transplant surgery. LT-beta expression in liver biopsy specimens was studied using quantitative real time polymerase chain reaction and immunohistochemistry. RESULTS: LT-beta mRNA levels were similar in control and HCV liver in the absence of fibrosis. In subjects with portal fibrosis, LT-beta mRNA levels were elevated 2.2-fold over control liver levels (p=0.04). In subjects with bridging fibrosis, LT-beta mRNA levels increased 4.4-fold over control liver levels (p=0.02). LT-beta mRNA levels in subjects with established cirrhosis were increased 3.3-fold compared with controls and 2.6-fold compared with mild liver damage (p=0.02). Immunohistochemical analysis established that LT-beta was expressed by oval cells, inflammatory cells, and small portal hepatocytes. CONCLUSIONS: In chronic HCV infection, LT-beta expression is observed in multiple hepatic cell types, including oval cells. LT-beta expression is significantly increased when fibrosis or cirrhosis is present, suggesting a role for LT-beta in the pathogenesis of chronic hepatitis C and a possible role in oval cell mediated liver regeneration.     

Immunohistochemical Studies on Structural Changes of the Hepatic Lobules in Chronic Liver Diseases

Liver biopsy specimens were examined immunohistochemically to clarify structural changes of the hepatic lobules in chronic liver diseases. In normal liver carbohydrate antigen 19-9 was located in the biliary ductular epithelium, whereas factor VIII-related antigen was observed in the endothelium of portal veins, hepatic arteries, and central veins. This antigen was not detected in the sinusoidal endothelium. In contrasts, monoclonal antibody OKM5 was reactive with the sinusoidal endothelium but was unreactive with the endothelium of the portal blood vessels or central veins. In chronic active hepatitis and liver cirrhosis, both carbohydrate antigen 19-9 positive biliary ductular cells and factor VIII-related antigen positive endothelial cells were not only observed in the enlarged portal area but also extended into the parenchyma. They were occasionally accompanied by fibers. These findings suggest that fibrosis, ductular epithelial, and blood vascular proliferation in the portal space and their invasion into the parenchyma might gradually cause structural changes of the hepatic lobules in chronic liver disease.