布加综合征诊治研究进展

<正>肝血管病是罕见的累及肝脏循环系统的异质性疾病,可累及肝动脉、门静脉、肝窦和肝静脉系统,主要包括布加综合征(Budd-Chiari syndrome, BCS)、门静脉血栓(portal vein thrombosis, PVT)、特发性非肝硬化性门静脉高压(idiopathic non-cirrhotic portal hypertension, INCPH)、     

特发性门脉高压的诊断和临床处理

特发性门脉高压(idiopathic portal hypertension,IPH)是门脉高压的罕见情况,以门脉高压的相关表现为主,肝功能正常,不伴肝静脉或门静脉梗阻。感染和血栓形成倾向分别是东方和西方IPH患者的首要致病因素。肝静脉压力梯度(hepatic vein pressure gradient,HVPG)、脾脏/肝脏硬度比值及肝活组织检查对鉴别特发性门脉高压与肝硬化门脉高压价值较大。IPH总体预后良好,门脉血栓形成可能提示预后不良。临床处理以防治静脉曲张出血为主,其原则大致与防治肝硬化门脉高压的静脉曲张出血相同。部分IPH患者需考虑手术分流及抗凝治疗。     

特发性门静脉高压症研究进展

自20世纪60年代以来,许多学者研究发现,某些原因不明的脾肿大和门静脉高压是由于门静脉纤维化使门静脉血流受阻、门静脉压升高而继发脾肿大,但一般并不发展成肝硬化,1962年印度学者Ramalingas Wami称之为非硬化性门脉纤维化(Non cihotic portal fibrosis NCPF),英国也沿用这一名称[1,2],1965年美国Mikkelsen称之为肝内门静脉硬化症(Hepatoportal sclerosis HPS),而在日本则称为特发性门静脉高压症(Idiopathic portal hypertension IPH)[1].     

门静脉高压症的发生机理

一、正常门静脉血流及门静脉压 门静脉是指脾静脉与肠系膜静脉汇合处起到肝门一段形成的总干,长约6～8cm。正常门静脉压力约0.8～1.33kPa,平均1.07kPa。门静脉压力虽然随着饮食或运动有一些差异,但都不超过1.33kPa。如果门静脉血流受阻,门脉压力升高到1.33kPa以上时,即成为门脉高压症(portal hypertension,PH),门脉高压时压力可高达2.7～4.0kPa。     

卡维地洛对肝硬化食管静脉曲张出血的预防作用

门静脉高压（portal hypertension,PH）是肝硬化的严重并发症之一,可以促进食管静脉曲张（esophageal varices,EV）、食管静脉破裂出血（esophageal varices bleeding,EVB）、门脉高压性胃病、腹水、肝肾综合征和肝性脑病等并发症的发生[1]。经药物或其他治疗后,门脉系统出现血流动力学应答,即肝静脉压力梯度（hepatic venous pressure gradient,HVPG）较基线值降低≥20%或降至≤12 mmHg,可以减少门脉高压相关并发症、尤其是食管静脉曲张出血及再出血的发生风险,最终提高肝硬化患者生存率[2-4]。     

门脉高压症的检查选择与病因诊断

正门脉高压症(portal hypertension,PHT)的定义为门静脉与下腔静脉压力差大于5 mmHg。由于门脉压力增加导致的全身内脏动脉血管扩张,高动力循环状态伴发门体侧支循环形成,加速相关并发症的发生。其常见的并发症包括食管胃静脉曲张破裂出血、脾功能亢进症、难治性腹水、肝性脑病、自发性细菌性腹膜炎等。一般认为食管胃静脉曲张破裂出血在肝静脉压力梯度(hepatic venous pressure     

隐源性非硬化性门脉高压症患者临床和肝组织病理学表现

正特发性非硬化性门脉高压症(Idiopathoc noncirrhotic portal hypertension,INCPH)是近来提出的名词,代替门脉性肝硬化、隐源性门脉高压、不完全间隔性硬化或再生性结节性增生(NRH)等,用来描述由于未知原因引起肝窦前性门脉高压,其特征是门脉高压(食管静脉曲张,非恶性腹水,侧枝循环),脾肿大,门静脉和肝静脉通畅,而没有临床和     

胰源性区域性门脉高压症46例的个体化治疗

区域性门脉高压症(regional portal hypertension,RPH),亦称“左侧门脉高压症”、“局限性门脉高压症”等,约占门静脉高压症患者的5％[1-2],但却是惟一可治愈的门脉高压症.     

非肝硬化性门脉高压的临床诊断

门静脉高压症是指各种原因导致的门静脉压力升高,临床表现为脾肿大、脾功能亢进症、食管胃底静脉曲张和腹水等临床症候群。根据病变部位的不同,门脉高压可分为肝前性、窦前性、窦性、窦后性和肝后性门脉高压[1]。引起门脉高压的最常见病因是肝硬化,属于窦性门脉高压,约占我国患者的80%~85%,而非肝硬化性门脉高压(non-cirrhotic portal hypertension,NCPH)是指患者有明显的门脉高压表现,但临床生化、影像学或组织学上无肝硬化证据的一组疾病,包括肝外门静脉闭塞症、先天性肝纤维化、特发性非硬化性门脉高压、肝窦阻塞综合征和布加综合征等[2]。NCPH患者与肝硬化门脉高压症患者在病因、治疗和预后方面有明显的不同,因此应重视对该组疾病的认识。本文对常见的NCPH疾病进行了简述,期待提高临床医生对该组疾病的认识。     

特发性门脉高压误诊为肝硬化1例报道

特发性门脉高压(idiopathic portal hypertension,IPH)是一种以门脉高压相关表现为主,肝功能正常,不伴肝静脉或门静脉梗阻的罕见疾病。本文报道1例将IPH误诊为肝硬化的病例,旨在引起临床医师的注意。     

Splanchnic Hemodynamics in Idiopathic Portal Hypertension: Comparison with Chronic Persistent Hepatitis

A comparative study of splanchnic hemodynamics was made in 12 patients with idiopathic portal hypertension and in eight patients with chronic persistent hepatitis, but without portal hypertension, who served as the control. Venous pressures were measured by portal and hepatic vein catheterizations, blood flow by the pulsed Doppler flowmeter, and organ volume by computed tomography. Splenic artery blood flow was 788 +/- 242 ml/min in idiopathic portal hypertension and about four times that in chronic persistent hepatitis (215 +/- 42 ml/min), whereas there was no difference in superior mesenteric artery blood flow between the former and the latter (408 +/- 142 vs. 389 +/- 32 ml/min). Spleen volume in idiopathic portal hypertension was six times that in chronic persistent hepatitis, and splenic artery blood flow showed a significant linear correlation with spleen volume in idiopathic portal hypertension (r = 0.71, p less than 0.02). The sum of splenic artery blood flow and superior mesenteric artery blood flow in idiopathic portal hypertension was 1195 +/- 294 ml/min, twice that in chronic persistent hepatitis (603 +/- 109 ml/min). Portal vascular resistance and intrahepatic portal vascular resistance were three times and four times those in chronic persistent hepatitis, respectively. These results indicate that both increased intrahepatic portal vascular resistance and increased splenic artery blood flow may play roles in the development of portal hypertension in idiopathic portal hypertension.     

门脉高压诊断现状及其治疗新进展

门脉高压是各种原因所致肝内血管阻力增大和门静脉血流量增加的结果,是肝硬化严重并发症(静脉曲张出血和顽固性腹水)的主要死亡原因,特别是在失代偿期肝硬化患者中,进行门脉高压早期评估、治疗及管理能够有效降低严重并发症发生率和患者病死率。目前测量肝静脉压力梯度是公认的评估门脉高压程度的金标准,近年来无创诊断评估手段层出不穷,但能够应用于临床的技术较少;针对门脉高压的治疗包括药物治疗、内镜治疗、微创介入、外科手术和肝移植等。本文就目前门脉高压的诊断及治疗新进展作一综述。     

Management of portal hypertension based on portal hemodynamics

Portal hypertension is most commonly caused by chronic liver disease. As liver damage progresses, portal pressure gradually elevates and hemodynamics of the portal system gradually change. In normal liver, venous returns from visceral organs join the portal trunk and flow into the liver (hepatopetal blood flow). As portal pressure increases due to liver damage, congestion of some veins of the visceral organ occurs (blood flow to and from). Finally, the direction of some veins (the left gastric vein in particular) of the visceral organ change (hepatofugal blood flow) and develop as collateral veins (portosystemic shunt) to reduce portal pressure. Therefore, esophagogastric varices serve as drainage veins for the portal venous system to reduce the portal pressure. In chronic liver disease, as intrahepatic vascular resistance is increased (backward flow theory) and collateral veins develop, adequate portal hypertension is required to maintain portal flow into the liver through an increase of blood flow into the portal venous system (forward flow theory). Splanchnic and systemic arterial vasodilatations increase the blood flow into the portal venous system (hyperdynamic state) and lead to portal hypertension and collateral formation. Hyperdynamic state, especially around the spleen, is detected in patients with portal hypertension. The spleen is a regulatory organ that maintains portal flow into the liver. In this review, surgical treatment, interventional radiology, endoscopic treatment, and pharmacotherapy for portal hypertension (esophagogastric varices in particular) are described based on the portal hemodynamics using schema.     

Noncirrhotic portal hypertension

Portal hypertension is characterized by an increase in portal pressure (>10 mm Hg) and could be a result of cirrhosis of the liver or noncirrhotic diseases. Noncirrhotic portal hypertension (NCPH), as it generally is termed, is a heterogeneous group of diseases that is due to intrahepatic or extrahepatic etiologies. In general, the lesions in NCPH are vascular in nature and can be classified based on the site of resistance to blood flow. Noncirrhotic portal fibrosis and extrahepatic portal vein obstruction are two diseases that are common in developing countries; they most often present only with features of portal hypertension and not of parenchymal dysfunction. These are described in detail.     

Increased blood flow through the portal system in cirrhotic rats

Portal venous pressure is the result of the interplay between portal venous blood flow and the vascular resistance offered to that flow. Whether portal hypertension is maintained only by an increased portal venous resistance or also by an increased blood flow within the portal venous system is still open to speculation. To resolve these differences, splanchnic and systemic hemodynamics were evaluated in cirrhotic rats, induced by CCl4. Blood flow and portal-systemic shunting were measured by radioactive microsphere techniques. All cirrhotic rats had portal hypertension (portal venous pressure 13.5 +/- 1.1 vs. 9.0 +/- 0.5 mmHg, in normal control rats; p less than 0.01), but portal-systemic shunting in cirrhosis (31% +/- 13% vs. 0.2% +/- 0.02%; p less than 0.05) was variable, ranging from 1% to 97%. Portal venous inflow, the total blood flow within the portal system, was increased in cirrhotic rats (5.75 +/- 0.04 vs. 4.52 +/- 0.36 ml/min per 100 g; p less than 0.05). Total splanchnic arterial resistance was reduced in cirrhotic rats (3.3 +/- 0.2 vs. 5.8 +/- 0.5 dyn X s X cm-5 X 10(5); p less than 0.01). Portal venous resistance, however, was not abnormally elevated in cirrhotic rats (4.6 +/- 0.5 vs. 4.7 +/- 0.5 dyn X s X cm-5 X 10(4), p = NS). Splanchnic hemodynamics in cirrhotic rats demonstrate that portal hypertension is maintained, at least in part, by a hyperdynamic portal venous inflow. The hemodynamic data in cirrhotic rats provided evidence that supports the role of an increased portal blood flow in portal hypertension and gives a quantitative definition of splanchnic hemodynamics in intrahepatic portal hypertension.     

重视门静脉高压的基础与临床研究

门静脉高压是指门静脉系统血流受阻和(或)血流量增加,导致门静脉及其属支血管内静水压持续升高。随着对门静脉高压基础研究的深入,进而更注重疾病并发症,如门静脉高压性胆病、门静脉高压性胃病、门静脉高压性肠病、异位静脉曲张、肝性脊髓病等的认知,最终提倡应早期预防门静脉高压并给予适当的介入治疗,因此就门静脉高压的相关诊治进展进行介绍。     

Reversal of portal hypertension and hyperdynamic splanchnic circulation by combined vascular endothelial growth factor and platelet-derived growth factor blockade in rats

Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) pathways are crucial to angiogenesis, a process that contributes significantly to the pathogenesis of portal hypertension. This study determined the effects of inhibition of VEGF and/or PDGF signaling on hyperdynamic splanchnic circulation and portosystemic collateralization in rats with completely established portal hypertension, thus mimicking the situation in patients. Portal vein-ligated rats were treated with rapamycin (VEGF signaling inhibitor), Gleevec (PDGF signaling inhibitor), or both simultaneously when portal hypertension was already fully developed. Hemodynamic studies were performed by transit-time flowmetry. The extent of portosystemic collaterals was measured by radioactive microspheres. The expression of angiogenesis mediators was determined by Western blotting and immunohistochemistry. Combined inhibition of VEGF and PDGF signaling significantly reduced splanchnic neovascularization (i.e., CD31 and VEGFR-2 expression) and pericyte coverage of neovessels (that is, alpha-smooth muscle actin and PDGFR-beta expression) and translated into hemodynamic effects as marked as a 40% decrease in portal pressure, a 30% decrease in superior mesenteric artery blood flow, and a 63% increase in superior mesenteric artery resistance, yielding a significant reversal of the hemodynamic changes provoked by portal hypertension in rats. Portosystemic collateralization was reduced as well. CONCLUSIONS: Our results provide new insights into how angiogenesis regulates portal hypertension by demonstrating that the maintenance of increased portal pressure, hyperkinetic circulation, splanchnic neovascularization, and portosystemic collateralization is regulated by VEGF and PDGF in portal hypertensive rats. Importantly, these findings also suggest that an extended antiangiogenic strategy (that is, targeting VEGF/endothelium and PDGF/pericytes) may be a novel approach to the treatment of portal hypertension.     

Effect of somatostatin on splanchnic hemodynamics in patients with liver cirrhosis and portal hypertension

The effect of somatostatin on splanchnic hemodynamics in patients with liver cirrhosis is not clearly defined, as some authors report a decrease in portal pressure and in liver blood flow during intravenous administration of this hormone, while others do not. In 19 subjects with liver cirrhosis and portal hypertension the following parameters were measured before and during intravenous administration of somatostatin (7.5 micrograms/min): porto-hepatic gradient, estimated hepatic blood flow, specific splenic blood flow, cardiac index. Estimated hepatic blood flow decreased significantly during somatostatin infusion (p less than 0.05), averaging a 13% decrease; porto-hepatic gradient, splenic specific blood flow and cardiac index did not vary significantly. These data indicate that somatostatin infused at a dose of 7.5 micrograms/min induces a slight decrease in liver blood flow without affecting portal hypertension.     

The pathophysiology of portal hypertension

Portal hypertension is defined by an elevation in blood pressure in the portal system. Different causes are known and include a pre-, intra-, or posthepatic block. Portal hypertension is also classified according to the sinusoidal system. Portal pressure becomes elevated by either an increase in blood flow (Q), an increase in resistance (R), or both. Regulation of the vascular tone in the splanchnic system includes intrinsic and extrinsic aspects. A variety of metabolic end-products (e.g. adenosine), endothelium-derived substances (e.g. nitric oxide), and certain neurotransmitters (e.g. acetylcholine) are known to relax the tone and thus produce vasodilation. Important vasoconstrictor influences on splanchnic arterioles include circulating agents (e.g. angiotensin), endothelium-derived substances (e.g. endothelin), and again neurotransmitters (norepinephrine). Besides vascular tone, structural changes (thrombosis, fibrosis, shear stress, and cell regeneration) add to overall hepatic resistance. Further consequences of portal hypertension include an increase in blood flow which leads to a hyperdynamic state with fluid retention, leading to secondary involvement of other organs, such as cirrhotic cardiomyopathy, hepatopulmonary syndrome and hepatorenal syndrome. Finally, portal hypertension will end up in the formation of collateral vessels. Varices can involve the whole gastrointestinal tract and are a frequent source of bleeding.     

儿童门静脉高压症研究进展

儿童门静脉高压症是指在多种病因作用下,门静脉系统的血流受阻和（或）血流量增加、血管舒缩功能障碍,引起门静脉及其属支的压力持续增高,门静脉压力＞5 mmHg（1 mmHg=0.133 kPa）,或门静脉、肝静脉压力梯度＞10 mmHg,最终导致脾大、门腔侧支循环形成和开放、腹水等临床表现,是一种血流动力学异常综合征。儿童门静脉高压症根据病因不同分为肝硬化性门静脉高压症和非肝硬化性门静脉高压症;根据压力来源的解剖部位,可将门静脉高压症分为肝前性、肝内性（窦前性、窦性、窦后性）及肝后性。治疗方法有药物治疗、曲张静脉套扎或硬化、手术治疗等。虽然儿童门静脉高压症发病率较低,但可以引起胃食管静脉曲张破裂出血、肝性脑病等严重并发症。为加强对本病的认识,减少并发症,提高治愈率,现将其病因分类、发病机制、诊断和治疗方面的研究进展作一综述。