特发性非硬化性门静脉高压诊治进展

特发性非硬化性门静脉高压是一组少见的临床综合征,它的特征是没有肝硬化的组织学表现但有门静脉高压的临床表现,并且排除已知的可以引起门静脉高压的肝内外原因。其病因和发病机制尚不明确,但是可以确定与肝内血管病变的发展有关。目前认为可能的致病机制包括：免疫紊乱、慢性感染、毒物或药物损伤、微血栓形成、基因异常等。最常见的临床表现...     

非肝硬化性门静脉高压症的研究现状

肝硬化是门静脉高压的最常见原因,但仍有约20%的门静脉高压继发于非肝硬化因素,称为非肝硬化性门静脉高压症(NCPH),在发展中国家发病率较高。NCPH是一组异源性的肝脏血管疾病,临床上多见的是特发性门静脉高压(IPH)、肝外门静脉血管阻塞(EHPVO),以及布加综合征、先天性肝纤维化和结节再生性增生等少见病。此类患者常常具有门静脉高压的证据,如反复发生的静脉曲张出血和脾脏肿大,但肝功能保存尚好。目前尚无诊断NCPH的统一标准,对其诊断仍是一个挑战。临床上往往采用排除性诊断,必要时可行肝穿刺活组织检查来确诊。介绍了IPH和EHPVO的发病机制、病理表现、诊断方法及治疗策略的选择,若能有效控制上消化道出血,NCPH被认为是预后相对良好的一类疾病。     

门静脉高压症血流动力学改变的发病机理

门静脉高压症（PHT）与肝内循环、体循环和门体侧支循环的血流动力学改变有关。肝内阻力增加和高动力循环侧支血管的扩张在门静脉高压的发病机理中起到了重要作用。不同严重程度的肝硬化均存在能广泛影响人体的血流动力学紊乱。门静脉高压和高动力循环是肝硬化患者发病和死亡的主要原因。而血管结构重塑和血管新生是治疗门静脉高压症的重要目标。     

特发性门静脉高压症1例

特发性门静脉高压症(IPH)是一类比较罕见的肝脏血管病变, 主要临床表现为肝内门静脉小分支的闭塞或狭窄诱发的门静脉高压。国内外研究显示, 该病与感染、药物、毒素、血栓倾向、免疫及遗传等因素相关。特发性门静脉高压又称特发性非肝硬化性门静脉高压症(INCPH), 为肝窦前性非肝硬化性门静脉高压, 较难与隐源性肝硬化相鉴别, 该病国内外鲜少报道。现报道1例人类白细胞DR3等位基因(HLA-DR3)阳性的IPH, 讨论该患者的诊治经过以及对该病的认识, 为临床提供借鉴。     

长期控制肝硬化门静脉高压症的策略

一、肝硬化门静脉高压症的自然史 门静脉高压症是指各种原因引起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压力升高,伴侧支循环形成的一组临床综合征,包括腹水、食管胃底静脉曲张出血(EVB)、肝性脑病、肝肾综合征、肝肺综合征、门静脉高压性胃病等[1].     

肝窦内皮细胞与门静脉高压

SECs是肝脏内一种具有特殊形态结构和生理功能的内皮细胞。在门静脉高压形成和发展过程中起重要作用，SECs参与肝纤维化和肝窦毛细血管化，SECs形态和功能异常，导致肝内血管收缩和舒张因子之间平衡失调，肝内血管阻力增加，是门静脉高压形成和发展和重要因素之一。本简要概述肝窦内皮细胞参与门静脉高压形成过程的机制。     

外源性血管内皮生长因子对肝硬化大鼠肝组织血管的影响

目的:研究外源性血管内皮生长因子对肝硬化大鼠肝脏组织内血管的影响,以检测肝硬化大鼠肝脏微循环变化.方法:25只肝硬化门静脉高压造模成功SD♂大鼠,体质量180-220 g,随机分为肝硬化门静脉高压对照组(B组,n=10)和肝硬化门静脉高压实验组(C组,n=15),C组应用Alzet微渗泵从大鼠门静脉连续泵入血管内皮生长...     

卡维地洛治疗肝硬化门静脉高压症的作用机制及应用现状

肝硬化门静脉高压症的形成依赖于肝内血管阻力的增加及血流高动力状态。卡维地洛因其特有的降低肝内血管阻力作用,理论上具有更好的降低门静脉高压的效果。归纳了卡维地洛降低门静脉高压已知及可能的机制,回顾了卡维地洛治疗肝硬化门静脉高压症的最新研究。认为卡维地洛有望成为治疗肝硬化门静脉高压症的核心药物,而他汀类药物可能成为其最佳搭档。     

肝窦内皮细胞与门静脉高压

SECs是肝脏内一种具有特殊形态结构和生理功能的内皮细胞,在门静脉高压形成和发展过程中起重要作用。SECs参与肝纤维化和肝窦毛细血管化,SECs形态和功能异常,导致肝内血管收缩和舒张因子之间平衡失调。肝内血管阻力增加,是门静脉高压形成和发展的重要因素之一。本文简要概述肝窦内皮细胞参与门静脉高压形成过程的机制。     

肝硬化门静脉高压的病因和非病因治疗

高压是肝硬化的严重并发症,是门静脉阻力和门静脉血流量增加的结果。病因和非病因治疗均可在一定程度上有效降低门静脉压力,但在改善预后方面效果欠佳。以降低肝内血管阻力为靶点的新治疗药物可能有助于实现门静脉高压的逆转。本文以肝硬化门静脉高压的发生机制为基础,对目前的药物治疗从病因和非病因治疗两方面进行总结,以期为临床治疗选择提供较全面的理论和循证依据。     

Hepatopulmonary syndrome and portopulmonary hypertension: recent knowledge in pathogenesis and overview of clinical assessment

Hepatopulmonary syndrome and portopulmonary hypertension are cardiopulmonary complications, which are not infrequently seen in patients with liver disease and/or portal hypertension. These entities are both clinically and pathophysiologically different: the hepatopulmonary syndrome is characterized by abnormal pulmonary vasodilation and right‐to‐left shunting resulting in gas exchange abnormalities, whereas portopulmonary hypertension is caused by pulmonary artery vasoconstriction leading to hemodynamic failure. As both hepatopulmonary syndrome and portopulmonary hypertension are associated with significantly increased morbidity and mortality, and as these patients are commonly asymptomatic, all liver transplantation candidates should be actively screened for the presence of these two complications. The aim of is this review is to provide an overview on the hepatopulmonary syndrome and portopulmonary hypertension with primary focus on diagnosis and recent knowledge regarding pathogenesis and therapeutic targets.     

Pulmonale Komplikationen der Leberzirrhose

Hepatopulmonary syndrome, portopulmonary hypertension and hepatic hydrothorax are typical pulmonary complications in patients with liver cirrhosis. Whereas hepatopulmonary syndrome and portopulmonary hypertension represent pulmonary vascular diseases, the development of hepatic hydrothorax is associated with the presence of ascites and phrenic lesions. For severe hepatopulmonary syndrome and refractory hepatic hydrothorax, liver transplantation is the treatment of choice. In severe portopulmonary hypertension specific medical treatment is indicated. In selected patients, beside intravenous prostanoids, oral endothelin receptor antagonists and phosphodiesterase type-5 inhibitors are possible treatment options.     

Hepatopulmonary syndrome and portopulmonary hypertension

Liver disease affects the lungs. The majority of patients exhibit mild to moderate arterial hypoxaemia essentially attributable to an alteration in ventilation/perfusion matching and limited by an increase in ventilation. A minority (some 10%) of patients exhibit a "hepatopulmonary syndrome" defined by severe hypoxaemia with arterial PO2 below 60 mm Hg, dyspnoea, cyanosis, digital clubbing, orthodeoxia, platypnoea and demonstrable pulmonary vascular dilatations causing a true pulmonary shunt and a diffusion/perfusion imbalance. The hepatopulmonary syndrome is incurable but resolves over time after liver transplantation. An even lower proportion of patients, approximately 1%, develop pulmonary hypertension. Clinically this "portopulmonary hypertension" resembles primary pulmonary hypertension, with dyspnoea and fatigue as the main symptoms, histopathology and response to prostacyclin therapy. Portopulmonary hypertension is irreversible. Liver transplantation mortality in patients with portopulmonary hypertension ranges from 50 to 100%. The common cause of the hepatopulmonary syndrome and portopulmonary hypertension is portal hypertension and portosystemic shunting, indicating that vasoactive and angiogenetic factors originating from the liver normally control the pulmonary circulation.     

Pulmonary vascular complications in portal hypertension and liver disease: A concise review

Chronic liver disease and/or portal hypertension may be associated with one of the two pulmonary vascular complications: portopulmonary hypertension and hepatopulmonary syndrome. These pulmonary vascular disorders are notoriously underdiagnosed; however, they have a substantial negative impact on survival and require special attention in order to understand their diagnostic approach and to select the best therapeutic options. Portopulmonary hypertension results from excessive vasoconstriction, vascular remodeling, and proliferative and thrombotic events within the pulmonary circulation that lead to progressive right ventricular failure and ultimately to death. On the other hand, abnormal intrapulmonary vascular dilations, profound hypoxemia, and a wide alveolar-arterial gradient are the hallmarks of the hepatopulmonary syndrome, resulting in difficult-to-treat hypoxemia. The aim of this review is to summarize the latest pathophysiologic concepts, diagnostic approach, therapy, and prognosis of portopulmonary hypertension and hepatopulmonary syndrome, as well as to discuss the role of liver transplantation as a definitive therapy in selected patients with these conditions.     

Pulmonary hypertension following hepatopulmonary syndrome in a patient with cirrhosis.

We report the case of a patient with liver cirrhosis who successively developed hepatopulmonary syndrome and portopulmonary hypertension. Initially, the patient presented with severe dyspnea and hypoxemia at rest. Technetium-99 macroaggregated albumin lung perfusion scan demonstrated right-to-left shunt, and hemodynamic study revealed a hyperdynamic state with low pulmonary vascular resistance, thus confirming the diagnosis of hepatopulmonary syndrome. More than 2 years after the onset of pulmonary symptoms, a marked improvement in dyspnea and gas exchange was observed. Lung perfusion scan did not disclose any right-to-left shunt and right-sided heart catheterization showed evidence of severe pulmonary hypertension. We conclude that hepatopulmonary syndrome and portopulmonary hypertension are not mutually exclusive. We hypothesize that, by reversing the phenomenon of intrapulmonary vasodilatation, the development of portopulmonary hypertension interfered with each of the potential causes of hypoxemia in hepatopulmonary syndrome (ventilation-perfusion inequalities, intrapulmonary shunting, oxygen diffusion limitation) and, as a result, led to a correction of hypoxemia.     

Portopulmonary hypertension and hepatopulmonary syndrome

The clinically and pathophysiologically distinct entities of portopulmonary hypertension and hepatopulmonary syndrome occur in a substantial proportion of patients who have advanced liver disease of different causes. These disorders are notoriously underdiagnosed, but they have a substantial impact on survival and require focused treatment. Abnormal intrapulmonary vascular dilatation, the hallmark of hepatopulmonary syndrome, can cause profound hypoxaemia that can be very difficult to treat. By contrast, portopulmonary hypertension results from excessive pulmonary vasoconstriction and vascular remodelling that eventually leads to right-heart failure. Insights into the pathogeneses of these syndromes have led to novel therapeutic approaches. However, in severely affected patients, effective treatment remains a difficult task. In selected patients, liver transplantation represents the only treatment option, but the decision to do isolated liver transplantation is particularly challenging in patients who have severe pulmonary disease involvement. Data from several centres have contributed to provide criteria that allow improved prediction of which patients may, or may not, benefit from liver transplantation alone.     

Portopulmonary hypertension

As a result of the success of orthotopic liver transplantation, there has been increasing interest in the diagnosis and therapeutic options for the pulmonary vascular complications of hepatic disease. These pulmonary vascular complications range from the hepatopulmonary syndrome, which is characterized by intrapulmonary vascular dilatations, to portopulmonary hypertension (POPH), which is characterized by an elevated pulmonary vascular resistance as a consequence of obstruction to pulmonary arterial blood flow. This review concentrates on POPH.     

Portopulmonary hypertension

The development of pulmonary arterial hypertension in the setting of portal hypertension is known as portopulmonary hypertension. Portal hypertension is thought to predispose patients to disturbances in the homeostatic regulation of numerous neurohumoral and vasoactive mediators that induce the development of pulmonary arterial hypertension. Portopulmonary hypertension is pathologically indistinguishable from idiopathic pulmonary arterial hypertension and is characterized by the development of vasoconstriction, vascular remodeling, and thrombosis within the pulmonary vasculature. Although described in patients with both cirrhotic and noncirrhotic portal hypertension, portopulmonary hypertension is most prevalent among patients with end-stage liver disease, and its severity seems to be independent of the etiology or severity of liver disease. All liver transplant candidates must be screened for the presence of portopulmonary hypertension because of the high perioperative mortality risk of liver transplantation associated with this condition. Primary screening for portopulmonary hypertension consists of Doppler-estimated pulmonary artery systolic pressure measurement during echocardiography. However, the diagnosis of portopulmonary hypertension is based on unique hemodynamic criteria as determined by right heart catheterization. Untreated portopulmonary hypertension portends a poor prognosis, and the efficacy of current treatment modalities is limited. At present, the primary goals of therapy are to provide symptomatic relief, prolong survival, and improve pulmonary hemodynamics to facilitate safe and successful liver transplantation.     

Severe portopulmonary hypertension after liver transplantation in a patient with preexisting hepatopulmonary syndrome

BACKGROUND: Portopulmonary hypertension and hepatopulmonary syndrome have been considered mutually exclusive pulmonary vascular disorders in liver disease states. METHODS: This current report describes a middle-aged patient, a candidate for liver transplantation, diagnosed with hepatopulmonary syndrome on the basis of clinical, echocardiographic and gas exchange criteria. Unusually high pulmonary pressures were observed at liver transplantation, performed 6 months after the initial diagnosis of hepatopulmonary syndrome. Three months later, the patient developed severe pulmonary hypertension and died of right ventricular failure during a second attempted liver transplantation. Postmortem histologic findings in the lung confirmed the presence of plexogenic pulmonary arteriopathy. CONCLUSION: This case illustrates the potential occurrence of hepatopulmonary syndrome and portopulmonary hypertension in the same patient, suggesting that the presence of hepatopulmonary syndrome may not preclude the development of portopulmonary hypertension.     

Antiphospholipid syndrome presenting as portopulmonary hypertension

The association of pulmonary hypertension with portal hypertension, also called portopulmonary hypertension, is a well-described condition. The pathogenesis of this association remains unclear. We describe a 34-year-old female patient with "primary antiphospholipid syndrome" and portopulmonary hypertension. Our finding supports that in situ microthrombosis associated with the presence of anticardiolipin antibodies could be the pathophysiologic explanation for both portal and pulmonary hypertension.