The hepatic extracellular matrix

The unique nature of the hepatic extracellular matrix (ECM) is predicted by the special configuration of the space of Disse. Whereas other epithelial organs have two basement membranes (BM) and a substantial ECM interposed between endothelial and epithelial cells, the liver lobule has no BM and only an attenuated ECM, consisting mostly of fibronectin (FN), some collagen type I, and minor quantities of types III, IV, V, and VI. This configuration, together with the abundant fenestrations and gaps of the sinusoidal endothelial cells, seems ideally suited to facilitate the rapid bidirectional exchange of macromolecules normally taking place between plasma and hepatocytes. During organogenesis, the liver anlage is vascularized by continuous capillaries with BM, but by day 13.5 of development (in the rat) the vessels in the immediate proximity of hepatocytes become fenestrated, lacking specialized junctions and BM, suggesting that the hepatocytes produce signals capable of modulating the endothelial phenotype. In regeneration, hepatocyte proliferation precedes vascular proliferation resulting in the formation of hepatocyte clusters that, temporarily, lack sinusoids. Eventually, vascular proliferation follows and the normal hepatocyte-vascular relationships are restored. During this period laminin synthesis by Ito cells is prominent. As soon as hepatocytes become stable, secretion of the sinusoid phenotype-maintaining factors resumes and laminin synthesis and secretion terminates. The interplay between extracellular matrix and liver cells is essential for normal homeostasis and its modification results in derranged hepatic function.Parts of this editorial have been adapted from: A. Martinez-Hernandez, P.S. Amenta. Morphology, localization and origin of the hepatic extracellular matrix. In: Zern MA, Reid L (eds) Extracellular matrix: chemistry, biology, and pathology with emphasis on the liver. Marcel Dekker, New York, (in press)     

肝硬化上消化道出血患者血浆TXB2、6—酮—PGF1α及vWF的变化

为进一步探讨肝硬化患者上消化道出血的发生机制及病理生理意义,采用ELISA方法分别定量测定40例肝硬化患者与10例对照组患者血浆血栓素B2（TXB2）、6－酮－前列腺素F1α（6－酮－PGF1α）及血管性假血友病因子（vWF）的水平。结果显示：肝硬化患者无上消化道出血组血浆TXB2水平、TXB2／6酮－PGF1α比值较对照组明显降低（P＜0．05）,较出血组显著增高（P＜0．05或0．01）;而血浆6－酮－PGF1α与vWF水平较对照组明显增高（P＜0．05或0．01）,较出血组显著降低（P＜0．05）。结果表明,肝硬化患者上消化道出血与血浆TXB2下降、6－酮－PGF1α升高及其比例衡有密切关系,vWF水平升高能反映肝硬化血管内皮损伤及上消化道出血倾向。     

肝硬化患者胰高糖素负荷的血c—AMP及血糖反应性观察

目的观察肝硬化患者对胰高糖素负荷后的血c-AMP及血糖反应能力.方法38例肝硬化患者按Child-Pugh肝功能分级,分为A级(10例),B级(14例),C级(14例)三个亚组.11例健康者为对照组.清晨空腹静卧,套管针肘静脉穿刺并固定15min后采集基础血c-AMP和血糖标本,即刻以每公斤体重2.5μg胰高糖素快速静脉注射(30s内),分别于注射后5,15,30及45min采集血c-AMP和血糖标本.以放射免疫法测定血浆c-AMP浓度.以葡萄糖氧化酶法测定血糖浓度.结果肝硬化各组与对照组比较,基础血浆c-AMP浓度均显著高于对照组,而基础血糖无显著差异.胰高糖素负荷后5min血浆c-AMP浓度即明显增高,于10～15min达高峰,多数达峰时间在10min;血糖于5min开始升高,15～30min达高峰,多数达峰时间在30min,肝硬化各组的血c-AMP及血糖反应曲线均低于对照组,且肝硬化严重程度愈重,血c-AMP及血糖反应曲线愈低,峰值血浆c-AMP及峰值血糖浓度,肝硬化总体(122.08±84.39pmol/ml,5.71±0.75mmol/LA级(148.07±85.08pmol/ml,6.25±0.48mmol/L)、B级(120.47±173.34pmol/ml,5.84±0.60mmol/L)及C级(83.04±50.96pmol/ml,5.11±0.67mmol/L)均显著低于对照组(219.47±173.34pmol/ml,7.28±0.89mmol/L),且随肝硬化严重程度增加而显著降低.结论肝硬化患者对胰高糖负荷的血c-AMP及血糖反应能力减弱,且随肝硬化严重程度增加而减弱.     

血清总胆汁酸检测在肝炎后肝硬化中的意义

目的：评估血清总胆汁酸（TBA）检测在肝炎后肝硬化诊断及判定预后中的意义。方法：将79例肝硬化患者根据Child Puph分级分3组,比较各组间血清TBA、TBil等值的差异及相关性,经治疗2月后再次Child Puph评分,根据不同预后（好转、恶化包括死亡）分组比较TBA等值。结果：肝炎后肝硬化患者血清TBA异常率高,值随Child分极而递增,预后较好组TBA值较低。讨论：血清TBA值能较特异地反应肝脏摄取、合成功能和分泌状态,在肝硬化诊断及判断预后中有一定的临床意义。     

肝硬化合并低氧血症26例临床研究

目的 对２６例肝硬化合并低氧血症患者进行血气分析,探讨肝硬化合并低氧血症的发病机理及发生率。方法 用美国生产的ＩＬ１３０６型血气分析仪,测定２６例肝硬化患者及８例正常人动脉血中ＰａＯ２、ＳａＯ２、ＰａＣＯ２及ｐＨ值。比较两组之间的差异。结果 研究组与对照组比较,研究组ＰａＯ２明显下降,Ｐ〈０．０１,研究组中低氧血症的发生率达５３．８％。结论 肝硬化如出现并发症或肝贮备功能下降者合并低氧血症发生率明     

自身腹水回输治疗肝硬化腹水机制的研究

目的 :探讨自身腹水回输治疗肝硬化腹水机制。方法 :将 40例常规治疗疗效不佳的肝硬化腹水病人随机分为两组 :实验组放腹水 2 0 0 0ml,其中 1 0 0 0ml静脉回输 ,再静脉注射速尿 6 0mg ;对照组放腹水 2 0 0 0ml,静脉点滴白蛋白 1 0g ,再静脉注射速尿 6 0mg。结果 :实验组术前、术后、术后第 4d血浆醛固酮 (ALD)、血浆心钠素 (ANF)、血浆内皮素 (ET)及术前、术后尿量、肾动脉血流量与对照组无明显差异 ;但是实验组血清白蛋白升高较稳定。结论 :自身腹水回输治疗肝硬化腹水的机制在于同时消除腹水和扩容两大治疗原则。由于有许多血管活性物质的参与 ,可能逆转了发生腹水的某些病理生理环节     

肝癌和肝硬化患者血清一氧化氮水平探讨

目的：探讨一氧化氮（NO）与肝癌及其合并症、肝硬化、肝功能分级及肝硬化并发症的关系。方法：应用化学比色法检测34例肝癌患者，45例肝硬化患者及20例正常人血清NO水平。结果：肝癌组血清NO显著高于肝硬化组及正常对照组；肝癌合并代偿期肝硬化血清NO高于合并慢性肝炎者；肝硬化组血清NO与正常对照组比较，差异有显著性；并且随肝功能Child-Pugh分级的增加而升高，A级与对照组比较无差异，B级与A级、B级与C级比较，差异有显著性。并发肝肾综合征、食管胃底静脉曲张破裂出血者较无并发症肝硬化者NO明显升高。结论：内源性NO在肝癌及肝硬化时合成增加，且与肝癌合并症、肝硬化病情严重程度及并发症的发生密切相关。血清NO测量有助于肝癌及肝硬化病情的临床评估及疗效观察。     

前列地尔治疗重症病毒性肝炎肝硬化所致氮质血症

目的 :探讨前列地尔对重症病毒性肝炎 (以下简称重型肝炎 )、肝硬化所致氮质血症的疗效。方法 :3 0例重症肝炎、肝硬化所致氮质血症患者随机分成两组 ,治疗组和对照组各 15例。在护肝、利尿等综合治疗的基础上 ,治疗组加用前列地尔 10 μg ,对照组加用多巴胺 2 0mg ,两组药物均溶于 10 %葡萄糖注射液 2 5 0mL中静脉滴注 ,qd ,疗程均为 4周。结果 :治疗组有效率 60 .0 % ,对照组有效率 3 3 .3 % (P <0 .0 5 )。治疗组血清肌酐、尿素氮、总胆红素比对照组下降明显 ,Na+比对照组上升明显 ,差异均有显著性 (P <0 .0 5 )。结论 :前列地尔对重症肝炎、肝硬化所致氮质血症有较好疗效。     

前列腺素E1脂微球载体制剂治疗肝硬化大量腹水42例疗效观察

目的观察前列腺素E1脂微球载体制剂(Lipo-PGE1)治疗肝硬化大量腹水的疗效.方法选择肝硬化大量腹水84例,分为两组,治疗组42例,用Lipo-PGE1联合综合护肝+利尿剂治疗;对照组42例采用综合护肝+利尿剂治疗.结果治疗组对肝硬化大量腹水治疗显效率和总有效率显著高于对照组(P＜0.001).Lipo-PGE1治疗前后的丙氨酸转氨酶(ALT)、天门冬酸氨基转移酶(AST),总胆红素(SB)、肌酐(Cr)等指标均在疗程结束时得到显著改善(P＜0.01).结论 Lipo-PGE1有一定退腹水作用,且具有保护肝细胞、促进肝细胞再生的作用.     

A Long-term Follow-up Study on Risk Factors for Hepatocellular Carcinoma among Japanese Patients with Liver Cirrhosis

To identify virological parameters (serostatus of hepatitis B surface antigen [HBsAg] and antibodies to hepatitis C virus [anti-HCV], HCV genotypes and HCV-RNA titer) and other clinico-biological and lifestyle variables that may influence or predict the development of hepatocellular carcinoma (HCC) in cirrhosis, we followed 100 cirrhotic patients without HCC, who visited Kyushu University Hospital between 1985 and 1987, until the end of 1995 (follow-up rate: 98%; average follow-up period: 5.3 years). After elimination of 4 patients who developed HCC or were censored within the initial 6 months, 37 (39%) out of 96 patients developed HCC during follow-up. As compared with HBsAg(+) patients, anti-HCV(+) HBsAg(–) patients demonstrated significantly elevated HCC risk (adjusted hazard ratio [HR]=5.85, 95% confidence interval [CI] 1.65–20.67). Genotype 1 HCV infection was not associated with increased risk compared with genotype 2 (HR = 0.64, 95% CI 0.21–1.99). For genotype 1 HCV infection, patients with HCV-RNA levels <1 Meq/ml tended to present lower risk than patients with ≥1 Meq/ml ( P = 0.03). Male sex, advanced Child's class, lower serum albumin, and higher serum aminotransferase and α-fetoprotein were also found to be strong predictors. Overall, drinking and smoking habits were not associated with significantly elevated risk. Among virological parameters, anti-HCV positivity and, possibly high HCV-RNA titer, were predictive of HCC occurrence in cirrhosis in our clinical setting.