慢性乙型肝炎患者血清肝纤维化指标与病理的关系

目的探讨慢性乙型肝炎患者血清肝纤维化指标透明质酸（HA）、Ⅳ型胶原（IV—C）、层粘连蛋白（LN）及Ⅲ型前胶原（PCⅢ）与肝脏病理的关系。方法慢性乙肝患者40例,行肝穿刺,制片,HE染色及浸银染色后作病理学检查;取血,分离血清,应用放射免疫法检测HA、IV—C、LN及PCⅢ水平,对肝组织进行炎症活动度分级（G）及纤维化分期（s）。结果40例慢性乙肝患者血清HA、Ⅳ-C、LN及PCⅢ水平随肝脏炎症活动度升高而升高,随肝组织纤维化程度的加重而升高。结论血清HA、Ⅳ-C、LN及PCⅢ水平与肝组织纤维化程度呈正相关。检测上述指标有助于判断肝炎疾病的严重程度,并能反映肝组织纤维化程度。     

血清肝纤维化标志物水平与肝组织炎症活动度纤维化程度的相关性分析

研究血清纤维化指标透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原(PCⅢ)及Ⅳ型胶原(Ⅳ-C)水平与肝组织病理分级、分期的相关性。用放射免疫法(RIA)检测600例乙型肝炎和肝炎肝硬化患者血清HA、LN、CⅣ、PCⅢ水平,同时进行肝组织活检,对肝组织进行炎症分级和纤维化分期检测。血清学指标水平与慢性肝炎发展阶段性一致,与肝组织炎症活动度及纤维化程度呈正相关。其中HA、CⅣ在病理分期中,从S1～S4期均依次大幅度升高,与S0相比(P<0.01),对早期肝纤维化诊断优于LN。而PCⅢ在反映肝纤维化时与S2期呈依次明显升高,可作为肝纤维化中、晚期辅助诊断。血清纤维化指标HA、LN、CⅣ、PCⅢ水平,对肝纤维化不同阶段做出相对准确的诊断,是目前了解肝纤维化程度检测指标之一。     

慢性乙型肝炎和肝硬化患者血清HA、LN、PCⅢ和Ⅳ-C水平与肝组织纤维化程度的关系

目的 探讨慢性乙型肝炎和肝硬化患者血清透明质酸（HA）、层粘连蛋白（LN）、Ⅲ型前胶原（PCⅢ）和Ⅳ型胶原（Ⅳ－C）在肝纤维化诊断中的应用价值。方法 采用放射免疫法检测150例慢性乙型肝炎和肝硬化患者血清HA、LN、PVⅢ和Ⅳ－C水平，并与活检肝组织纤维化程度进行相关性分析。结果 各组慢性乙型肝炎患者血清HA、LN、PCⅢ和Ⅳ－C水平均高于正常对照组，与肝纤维化活动水平及程度呈密切正相关。结论 血清HA、LN、PCⅢ和Ⅳ－C水平能较好地反映乙型肝炎纤维化程度，联合检测可明显提高肝纤维化诊断的准确性和可靠性。     

血清纤维化指标对肝纤维化诊断价值的研究

目的评价血清纤维化指标透明质酸（HA）、Ⅳ型胶原（CⅣ）、Ⅲ型前胶原肽（PⅢP）、层黏连蛋白（LN）对肝纤维化诊断的价值.方法对确诊的慢性乙型肝炎患者50例和健康人18例,测定血清纤维化指标水平,并进行肝组织纤维化分期.根据受试者工作特征曲线判别4项指标对于肝纤维化分期的诊断价值.结果血清HA、CⅣ、PⅢP和肝脏组织炎症分级呈较弱正相关（r分别为0.430、0.382和0.300,P＜0.05）.血清HA、CⅣ与肝脏组织纤维化分期呈中度正相关（r分别为0.614、0.708,P＜0.05）.血清HA、CⅣ水平随肝纤维化的进展程度而升高.血清HA诊断早期肝硬化（S4）的受试者工作特征曲线下面积（AUC）大于血清CⅣ、PⅢP和LN（AUC=0.967比0.932、0.659、0.403）.血清CⅣ诊断肝纤维化（S1～S4）的AUC大于血清HA、PⅢP和LN（AUC=0.853比0.680、0.536、0.487）.血清LN对于肝组织分级或分期均无统计学意义.联合HA＋CⅣ检测比单一指标有更高的特异度.结论血清纤维化指标对肝纤维化进程有一定的预测意义,但不能对肝纤维化精确分期,因此不能取代肝组织病理活检.联合多项指标检测可在一定程度上提高检测效率.寻找新的血清标志物和联合其他标志物是肝纤维化无创性研究的趋势所在.     

慢性病毒性肝炎血清纤维化诊断指标评估

目的 评估血清透明质酸（HA）、Ⅲ型前胶原肽（PCⅢ）、层粘蛋白（LN）、Ⅳ型胶原（Ⅳ－C）对病毒性肝炎肝硬化的诊断意义。方法 检测129例慢性病毒性肝炎患者血清HA、PCⅢ、LN、Ⅳ－C水平,同时每例均行肝穿刺活检,以了解血清上述指标与肝脏病理炎症分级和纤维化分期的关系,并通过受试者特征工作曲线（ROC）评价它们对肝纤维化的诊断价值。结果 随肝脏炎症及纤维化程度加重,各项指标逐渐升高。ROC曲线下面积分析HA0．8204、LN0．7586、Ⅳ－C0．7090、PCⅢ0．6891。结论 四项指标对肝硬化均有一定诊断价值,其中HA优于其它指标。     

常用血清学指标与慢性乙型肝炎肝纤维化程度相关性研究

目的：研究常用血清学指标与慢性乙型肝炎肝纤维化程度的关系。方法：对177例慢性乙型肝炎患者进行血清肝脏生化和肝纤维化指标检测，包括丙氨酸氨基转移酶（AIT）、天冬氨酸氨基转移酶（AST）、碱性磷酸酶（ALP）、总胆红素（TBil）、白蛋白（Alb）、球蛋白（Glo）、透明质酸（HA）、层粘连蛋白（LN）、Ⅲ型前胶原蛋白（PcⅢ）、Ⅳ型胶原蛋白（CⅣ）。所有病例均行肝穿刺活检，并进行肝组织纤维化分期（S）。结果：部分血清学指标与肝组织纤维化程度相关，以Alb、Glo、HA、PCⅢ、CⅣ相关性最好，相关系数分别为-0．299、0．282、0．595、0．387、0．480。伴随肝纤维化程度的增加，血清白蛋白呈下降趋势，而血清球蛋白、HA、PCⅢ、CⅣ呈上升趋势。结论：部分血清学指标能反映肝组织纤维化程度，对于难以开展肝穿刺活检的单位可以帮助肝纤维化诊断。     

肝病患者纤维化不同分期时肝左叶上下径和前后径的测定及意义

目的研究慢性肝炎患者纤维化不同分期时肝左叶上下径、前后径的变化规律及其联合血清纤维化指标对无创诊断中晚期肝纤维化或早期肝硬化的价值。方法经肝活检确定72例慢性肝炎患者肝纤维化分期。肝穿前一日,B超测定肝左叶上下径、前后径等及肝穿刺点定位。放射免疫法测定血清HA、LN、CⅣ和PCⅢ含量。结果随纤维化程度增加,肝左叶上下径呈缩短趋势,其S4期测值为（5.7±1.5）cm明显短于S0期测值（7.7±1.4）cm;肝左叶前后径呈增长趋势,其S4期测值长于S0期分别为（6.5±1.1）cm和（5.3±0.7）cm。血清HA、LN、CⅣ和PCⅢ含量亦随纤维化增加而升高,HA、PCⅢ在S3期开始显著升高,均高于同组S0期［（273.4±131.3）μg/L对（66.2±35.0）μg/L、（167.4±48.1）μg/L对（103.4±23.8）μg/L］。结论肝左叶上下径、前后径及血清HA、PCⅢ含量变化可能间接反映了活动性肝纤维化中晚期或早期肝硬化。     

血清纤维化指标与慢性肝病的关系

目的：探讨血清纤维化指标透明质酸（HA）、层粘蛋白（LN）和Ⅲ型前胶原（PCⅢ）水平与慢性肝病的关系。方法：用放射免疫法测定96例慢性肝病患者血清HA、LN和PCⅢ水平，同时行肝组织活检，对肝组织进行炎症分级和纤维化分期。分析血清纤维化指标水平与肝组织分级和分期间的关系。结果：血清HA、LN和PCⅢ水平随慢性肝病的进展均逐渐升高，在慢性重度肝炎和肝硬化时达高峰，与肝组织炎症坏死和纤维化程度呈正相关。结论：血清HA、LN和PCⅢ水平可作为肝纤维化程度的指标之一。     

血清HA、LN、PCⅢ含量与慢性肝炎病理变化的关系

目的：了解血清肝纤维化指标透明质酸（ＨＡ）、层粘蛋白（LN）、Ⅲ型前胶原（PCⅢ）水平与慢性肝炎病理变化的关系。方法：用放射免疫法测定了13例慢性肝炎患者血清HA,LN,PCⅢ水平,同时行肝组织活检,病理切片,对肝组织进行炎症分级和纤维化分期,分析血清指标与病理分级、分期的关系。结果：将上述3项指标含量与慢性肝炎中度、肝硬变是改变对应观察,发现其与肝组织炎症分级和纤维化分期呈正相关。以HA上升幅度大、敏感度高、LN在S4期才升高幅度明显,PCⅢ主要是反映肝内成纤维活动的指标。病理变化与2项或3项异常符合率分别是38．5％与61．5％,提示血清HA、LN,PCⅢ含量能够反映慢性肝炎的严重程度,但其单项指标反映炎症活动度与纤维化程度的特异性、敏感性差、结论：开展HA、LN、PCⅢ水平的联合检测有助于提高肝纤维化的早期诊断。     

联合检测血清肝纤维化指标及总胆汁酸在慢性肝病诊断中的价值

目的：探讨慢性肝病患者血清透明质酸（HA）、Ⅲ型前胶原（PCⅢ）、Ⅳ型胶原（Ⅳ-C）、层粘连蛋白（LN）和总胆汁酸（TBA）水平及其临床意义。方法：应用放射免疫法和酶法分别检测171例慢性肝病毒患者的血清HA、PCⅢ、Ⅳ-C、LN及TBA水平升高有显著差异（P＜0．01）,除慢性肝炎轻度组血清LN水平与对照组无差异（P＞0．05）外,其余各组患者血清HA、PCⅢ、Ⅳ－C、LN、TBA水平均随病程的延长而逐渐升高。结论：联合检测慢性肝病患者血清HA、PCⅢ、Ⅳ-C、LN、TBA水平即能反映肝纤维化的轻重,又能了解肝细胞炎症活动及损害程度,对临床诊断、治疗及预后判为有重要价值。     

Pediatric vascular tumors of the liver:Review from the pathologist’s point of view

Differential diagnosis of pediatric vascular liver tumors can be challenging due to inconsistent nomenclature, histologic overlap and the rarity of some entities. Here we give an up-to-date overview of the most important entities. We discuss the clinic, histology and pathophysiology of hepatic congenital and infantile heman-gioma, hepatic epithelioid hemangioendothelioma and hepatic angio-sarcoma.     

肝星状细胞及相关细胞因子在肝纤维化形成中的作用

肝纤维化(hepatic fibrosis)是指肝脏内弥漫性细胞外基质(extracellular matrix,ECM)过度沉积的病理过程.肝星状细胞(hepatic stellate cells,HSC)被认为是ECM的主要来源细胞,在肝纤维化发生发展中起着关键作用.另外,各种病因引起肝细胞损伤时,Kupffers细胞(KF),肝窦内皮细胞等分泌一系列细胞因子,通过旁分泌和自分泌方式作用于邻近的HSC,影响其增殖,趋化和ECM代谢.因此,HSC及细胞因子与肝纤维化的发生发展关系极为密切,阐明其关系,有助于以HSC为靶点的肝纤维化方面的研究,现就其关系分别综述如下.     

Resection of the liver for colorectal carcinoma metastases

In this review of a collected series of patients undergoing hepatic resection for colorectal metastases, 100 patients were found to have survived greater than five years from the time of resection. Of these 100 long-term survivors, 71 remain disease-free through the last follow-up, 19 recurred prior to five years, and ten recurred after five years. Patient characteristics that may have contributed to survival were examined. Procedures performed included five trisegmentectomies, 32 lobectomies, 16 left lateral segmentectomies, and 45 wedge resections. The margin of resection was recorded in 27 patients, one of whom had a positive margin, nine of whom had a less than or equal to 1-cm margin, and 17 of whom had a greater than 1-cm margin. Eighty-one patients had a solitary metastasis to the liver, 11 patients had two metastases, one patient had three metastases, and four patients had four metastases. Thirty patients had Stage C primary carcinoma, 40 had Stage B primary carcinoma, and one had Stage A primarycarcinoma. The disease-free interval from the time of colon resection to the time of liver resection was less than one year in 65 patients, and greater than one year in 34 patients. Three patients had bilobar metastases. Four of the patients had extrahepatic disease resected simultaneously with the liver resection. Though several contraindications to hepatic resection have been proposed in the past, five-year survival has been found in patients with extrahepatic disease resected simultaneously, patients with bilobar metastases, patients with multiple metastases, and patients with positive margins. Five-year disease-free survivors are also present in each of these subsets. It is concluded that five-year survival is possible in the presence of reported contraindications to resection, and therefore that the decision to resect the liver must be individualized. John Radcliffe Infirmary, Oxford, England Read at the meeting of the American Society of Colon and Rectal Surgeons, Washington, D.C., April 5 to 10, 1987. Supported in part by Cooper Laser Sonics, Inc.     

晚期肝癌的一种新的有效治疗方法——反复暂时性肝动脉门静脉阻断并介入治疗

在反复暂时性肝动脉阻断治疗肝癌的基础上,作者设计了反复暂时性肝动脉、门静脉阻断并双介入治疗方法对12例晚期肝癌患者晚期患者进行了临床观察,发现患者经去血供等介入治疗后,临床症状改善,AFP 下降,生活质量提高,生存期明显延长。本方法既发挥反复暂时性肝动脉阻断治疗肝癌的优点,又可以阻断肿瘤内的门脉供血,同时配合双介入治疗,对门静脉癌栓有一定效果,因此不失为晚期肿癌的一种新的有效的辅助治疗方法。     

柏—查综合征的病因学探讨

目的 对柏－查综合征的病因进行探讨,方法对１３例柏－查综合征患者行手术探查并行直视隔膜切除及下腔静脉重建术。对切除标本进行光镜,电镜及免疫组化观察。结果 术中探查肝后段下腔静脉梗阻膜厚度２－２０ｍｍ。有７例合并血栓形成,有３例血栓延伸至静脉根部。光镜观察血管壁呈纤维组织增生,透明或黏液变性,９例有慢性炎性细胞浸润。     

Regulation of hepatic blood flow: the hepatic arterial buffer response revisited

The interest in the liver dates back to ancient times when it was considered to be the seat of life processes. The liver is indeed essential to life,not only due to its complex functions in biosynthesis,metabolism and clearance,but also its dramatic role as the blood volume reservoir. Among parenchymal organs,blood flow to the liver is unique due to the dual supply from the portal vein and the hepatic artery. Knowledge of the mutual communication of both the hepatic artery and the portal vein is essential to understand hepatic physiology and pathophysiology. To distinguish the individual importance of each of these inflows in normal and abnormal states is still a challenging task and the subject of on-going research. A central mechanism that controls and allows constancy of hepatic blood flow is the hepatic arterial buffer response. The current paper reviews the relevance of this intimate hepatic blood flow regulatory system in health and disease. We exclusively focus on the endogenous interrelationship between the hepatic arterial and portal venous inflow circuits in liver resection and transplantation,as well as inflammatory and chronic liver diseases. We do not consider the hepatic microvascular anatomy,as this has been the subject of another recent review.     

大鼠纤维化肝组织中PTEN的动态表达及其与肝星状细胞增殖和活化的关系

目的 探讨第10号染色体缺失的磷酸酶张力蛋白同源物基因(PTEN)在大鼠纤维化肝组织中的动态表达及其对在体肝星状细胞(HSC)活化、增殖的影响. 方法 采用胆总管结扎法建立大鼠肝纤维化模型;应用免疫组织化学染色、Western blot和实时荧光定量PCR技术测定大鼠肝组织中PTEN的表达;应用免疫荧光双标记共聚焦激光扫描显微术测定大鼠肝组织中活化HSC的PTEN表达;采用免疫组织化学染色检测大鼠肝组织中α-平滑肌肌动蛋白的表达.结果 免疫组织化学染色显示正常大鼠肝组织中PTEN有广泛表达,主要表达于细胞质,随着肝纤维化的发展,PTEN表达逐渐减少(P<0.01),而α-平滑肌肌动蛋白阳性细胞明显增多(P<0.01);造模1、2、3周及4周不同时间大鼠纤维化肝组织中PTEN的mRNA(分别为假手术组的0.66、0.53、0.44和0.37)及蛋白质表达(吸光度比值分别为1.20±0.13,1.07±0.16,0.88±0.08,0.73±0.07)均低于假手术组(P<0.01),并随着肝纤维化的进展逐渐降低(P<0.01);免疫荧光双标记共聚焦激光扫描显微术显示PTEN在活化HSC广泛表达,主要表达于细胞质,随着肝纤维化的进展,表达PTEN的活化HSC占总的活化HSC的比例逐渐减少(P<0.01). 结论 大鼠纤维化肝组织中PTEN的mRNA及蛋白质表达均下调;在体HSC的PTEN表达亦降低;肝组织中PTEN的动态表达与HSC的活化、增殖呈显著负相关.     

Usefulness of autotaxin for the complications of liver cirrhosis

BACKGROUND Autotaxin(ATX) has been reported as a direct biomarker for estimating the evaluation of liver fibrosis. But available data on ATX as a useful biomarker for the complications of liver cirrhosis(LC) are scant.AIM To assess the clinical usefulness of ATX for assessing the complications of LC.METHODS This multicenter, retrospective study was conducted at six locations in Japan. We include patients with LC, n = 400. The ATX level was evaluated separately in men and women because of its high level in female patients. To assess the clinical usefulness of ATX for the complications of LC, the area under the curve(AUC) of ATX assessing for the severe complications was analyzed in comparison with the model for end-stage liver disease score, albumin-bilirubin(ALBI) score, fibrosis-4 index, and aspartate aminotransferase-to-platelet ratio index.RESULTS The mean age was 68.4 ± 11.4 years, 240 patients(60.0%) were male. A total of 213(53.3%) and 187(46.8%) patients were compensated and decompensated,respectively. The numbers of patients with varix rupture, hepatic ascites, and hepatic encephalopathy were 35(8.8%), 131(32.8%), and 103(25.8%),respectively. The AUCs of ATX in men for hepatic encephalopathy, hepatic ascites, and varix ruptures were 0.853, 0.816, and 0.706, respectively. The AUCs of ATX in women for hepatic encephalopathy, hepatic ascites, and varix rupture were 0.759, 0.717, and 0.697, respectively. The AUCs of ATX in men were higher than those in women, as were all the other biomarkers used to detect encephalopathy and varix ruptures. However, for detecting ascites, the AUC of ALBI in men was more effective than using ATX.CONCLUSION ATX in men was more effective than any other biomarkers for detecting hepatic encephalopathy and varix ruptures.     

核糖体S6激酶与大鼠肝纤维化相关性研究

目的　探讨核糖体S6激酶(RSK)在大鼠肝纤维化发生中的作用。方法　采用腹腔注射二甲基亚硝胺的方法构建大鼠实验性肝纤维化模型。以免疫荧光双标记 激光扫描共聚焦显微镜成像技术检测RSK与α-平滑肌肌动蛋白(α- SMA)及Ⅰ型胶原。进一步利用免疫组化法检测 RSK与Ⅰ、Ⅲ型胶原在肝纤维化组织中的表达及其相关性。结果　在纤维化肝组织中,RSK的定位与α-SMA完全一致,Ⅰ型胶原伴随RSK周围分布。RSK与Ⅰ、Ⅲ型胶原的表达量之间亦呈显著相关(P<0.05)。结论　肝纤维化发生中,RSK定位于活化的肝星状细胞内,并参与胶原的表达调控。RSK可能成为治疗肝纤维化的新靶点。     

拉米夫定对慢性乙型肝炎肝纤维化的治疗作用(I)对血清肝纤维化指标的影响

目的　探讨拉米夫定治疗慢性乙型肝炎对血清肝纤维化指标的影响。方法　对 40例慢性乙型肝炎服药0、3、6、9、12个月进行动态测定血清透明质酸 (HA)、层粘蛋白 (LN )、Ⅲ型前胶原 (PⅢP)和Ⅳ型胶原 (ⅣC)。结果　 4项血清肝纤维化指标随着治疗时间延长不断下降 ,第 12个月时最明显 ,其中以HA最为显著 ,6个月复常率为 3 6.4% (8/2 2 ,P <0 .0 5 ) ,12个月复常率为 81.8% (18/ 2 2 ,P <0 .0 1) ,与ALT、AST复常率具有很好的相关性。按血清学疗效标准评价 ,6个月显效为 12 .5 % (5 / 40 ) ,有效为 12 .5 % (5 / 40 ) ,总有效率为 2 5 % (10 / 40 ) ;12个月显效为 42 .5 % (17/ 40 ,P <0 .0 5 ) ,有效为 2 7.5 % (11/ 40 ) ,总有效率为 70 % (2 8/ 40 ,P <0 .0 1)。结论拉米夫定治疗慢性乙型肝炎具有较好的近期抗肝纤维化作用。