Screen for portopulmonary hypertension, especially in liver transplant candidates

Pulmonary artery hypertension may develop in some patients with liver disease and portal hypertension. Although pulmonary artery hypertension may be asymptomatic in its early stages, it should be looked for especially if a patient is a candidate for liver transplantation, as it may make transplantation riskier.     

Respiratory dysfunction and pulmonary disease in cirrhosis and other hepatic disorders

End-stage liver disease and its complications are a leading cause of death among adults in the United States, and thousands of patients await liver transplantation. The liver plays a central role in health and homeostasis and thus the diseased liver leads to many deleterious effects on multiple organ systems, including the pulmonary system. We review the general effects of cirrhosis on the respiratory system, including mild hypoxemia, atelectasis, and hepatic hydrothorax. Cirrhosis is associated with 2 unique entities that affect the pulmonary vasculature: hepatopulmonary syndrome and portopulmonary hypertension. Hepatopulmonary syndrome, which is found in approximately 20% of patients awaiting liver transplantation, refers to the triad of hepatic dysfunction, hypoxemia, and intrapulmonary vascular dilations, and responds well to liver transplantation. In portopulmonary hypertension, cirrhosis and portal hypertension lead to pulmonary arterial hypertension, and portopulmonary hypertension has been considered a contraindication for transplantation. Currently, patients must have mild to moderate pulmonary hypertension to be considered for transplantation, and may still require long-term therapy with vasodilators to prevent right-ventricular failure and, consequently, failure of the newly transplanted liver allograft.     

肝移植过程中肺动脉高压的处理(英文)

背景:严重肝功能损害时可出现肺动脉压升高,而肝移植过程中特别是新肝开放时的血流动力学波动也会直接导致肺动脉压力的改变。目的:观察肝移植过程中肺动脉压力的变化,以及出现肺动脉高压时的处理。设计、时间及地点:选择2004-06/2006-06解放军第一八一医院进行肝移植手术的患者为观察对象进行前后对照观察。对象:择期行同种异体肝移植的终末肝病患者13例,均为男性,年龄19～53岁。方法:全身麻醉后应用有创技术及漂浮导管连续监测患者术中平均动脉压、中心静脉压、肺动脉压、肺动脉楔压,通过有效的呼吸管理和持续泵注小剂量硝酸甘油0.1～5.0μg/(kg·min),间断给予前列腺素E11.0～2.0μg/次,以降低术中门静脉开放时升高的肺动脉压及肺动脉楔压。主要观察指标:平均动脉压和肺动脉压变化。结果:13例肝移植患者移植过程中门静脉开放时均发生不同程度平均动脉压下降,肺动脉压、肺动脉楔压在门静脉开放后5,15min明显高于开放前(P<0.05)。运用硝酸甘油及前列腺素E1后肺动脉压、肺动脉楔压30min左右恢复到开放前水平。结论:肝移植过程中合理应用硝酸甘油、前列腺素E1能明显缓解门静脉开放时的肺动脉高压。     

Increased heme oxygenase-1 gene expression in the livers of patients with portal hypertension due to severe hepatic cirrhosis

Surgical bleeding associated with splanchnic hyperaemia due to portal hypertension complicates the anaesthetic management of hepatic transplantation. Although the mechanism(s) of portal hypertension are not fully understood, carbon monoxide, a product of the heme oxygenase (HO) reaction, is thought to be one of the endogenous vasodilators in the liver. In this study, the expression of mRNA encoding inducible HO isozyme (HO-1) in the livers of patients with portal hypertension undergoing hepatic transplantation was determined in comparison with those without portal hypertension. HO-1 mRNA levels were significantly greater in the portal hypertension group than in the group without portal hypertension. In contrast with HO-1, the gene expression of non-specific delta-amino-levulinate synthase (ALAS-N), which is down-regulated by heme in the liver, was the same in both groups. These results suggest that HO-1 is up-regulated through heme-independent stimuli according to the development of portal hypertension, and that induced HO-1 plays a pathophysiological role in portal hypertension through carbon monoxide production.     

Pulmonary hypertension complicating portal hypertension: portopulmonary hypertension]

Portopulmonary hypertension is a condition with a poor prognosis, which is defined as precapillary pulmonary hypertension complicating portal hypertension mainly due to cirrhosis of various etiologies. A mean pulmonary arterial pressure greater than 25 mmHg at rest with a pulmonary capillary wedge pressure less than 15 mmHg and a pulmonary vascular resistance greater than 120 dynes.sec.cm-5, in the setting of the presence of portosystemic shunting has been proposed as hemodynamic criteria for portopulmonary hypertension. Prevalence of pulmonary hypertension ascertained by right cardiac catheterization was 2% among patients with cirrhosis, and reached to 4% particularly among candidates for liver transplantation. Hyperdynamic systemic circulation seen commonly in patients with cirrhosis appeared to be normalized by complication of pulmonary hypertension with a contraction of circulating plasma volume. Long term treatment by epoprostenol administration or nitric oxide inhalation could induce a gradual decline in pulmonary arterial pressure in patients with poor response to acute vasodilator administration.     

肝移植术治疗肝功能C级门脉高压症患者的疗效分析

目的:分析肝功能C级的门脉高压症患者进行肝移植后的临床效果.方法:对306例肝功能C级的门脉高压症患者的肝移植治疗效果进行回顾性分析,术后随访12～48个月,观察病死率、食管胃底静脉曲张情况及再出血率.结果:306例患者病死率为10.1%,食管胃底静脉曲张消失率73.9%,再出血率2.0%.结论:肝移植是治疗肝功能C级门脉高压症患者的有效治疗手段.     

对比增强超声心动图对拟肝移植患者肺内分流的评估价值

背景：晚期肝病患者的肺内血管异常可以导致肺内右向左分流及严重低氧血症，目前国内对筛查肺内血管扩张尚缺乏一种简便、敏感、有效的方法。 目的：评估对比增强超声心动图对晚期肝病肺内分流的临床诊断价值。 设计、时间及地点：前瞻性病例对比观察，于2004-02／2006-02在解放军第四五八医院肝病中心完成。 对象：解放军第四五八医院肝病中心收治的男性拟行肝移植的晚期肝病患者24例。 方法：在无任何血管扩张药治疗情况下例行常规检查。采用对比增强超声心动图筛查晚期肝病患者肺内右向左分流的发生率，并根据左心室微泡的显示程度半定量分析记录为1^＋～3^＋。将患者分为经超声心动图证实有肺内分流组和无肺内分流组。 主要观察指标：拟行肝移植的晚期肝病患者肺内右向左分流的发生率及临床特点。结果：①24例患者中10例（41．7％）经对比增强超声心动图证实肺内右向左分流，左心室显影异常程度1^＋～2^＋，其中6例1^＋，4例2^＋，出现在右心室显影后6～10余个心动周期。②两组患者的年龄、性别、动脉血气分析指标、肝功能指标差异无显著性意义（P〉0．05）。③经超声心动图证实肺内分流组患者的上消化道出血发生率、门脉高压指征脾脏厚度及右心功能参数肺动脉收缩压、Tei指数均高于无肺内分流组（P〈0．05～0．01）。 结论：晚期肝病合并肺内分流而无低氧血症时肺血管扩张比较常见，对比增强超声心动图为诊断肺内血管扩张提供了一种敏感、非创伤的早期检查手段。门脉高压症是发生肺内血管扩张的主要因素，右心室Tei指数可作为评估肺内血管扩张患者右心功能的重要参数。     

Portopulmonary Hypertension in Nontransplanted Patients: Results of the Largest US Single-Institution Registry

ObjectiveTo explore clinical characteristics, risk profiles, and outcomes of patients with portopulmonary hypertension (PoPH) who have contraindications to liver transplant (LT).MethodsFrom the largest US single-institution registry of patients with PoPH, we analyzed 160 patients who did not receive LT between 1988 to 2019. Pulmonary arterial hypertension (PAH)–pertinent characteristics, hemodynamic features, treatments, and risk stratification were compared at baseline, first follow-up visit, and censor/death time.ResultsMedian survival for the entire cohort was 27.5 months from the diagnosis of PoPH. Overall survival was 89%, 77%, 51%, and 38% at 6 months, 1 year, 3 years, and 5 years, respectively. Survival was significantly affected by the severity of liver disease (P<.001). Most patients received PAH-specific therapies (136 [85%]), predominantly monotherapy (123 [77%)]. With treatment, significant improvements were noted in World Health Organization functional class (P=.04), 6-minute walk distance (P<.001), right ventricular function (P<.001), pulmonary vascular resistance (P<.001), and Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL) Lite 2 score (P=.02) univariately. Per European Society of Cardiology risk stratification, no patient met full criteria for low risk at baseline or at follow-up. In a multivariate Cox risk model, 6-minute walk distance, right atrial pressure, pulmonary capillary wedge pressure, bilirubin level, and Model for End-Stage Liver Disease–sodium score of 15 or higher were associated with increased risk of death.ConclusionPatients with PoPH who did not undergo LT had a poor prognosis. This persisted despite use of PAH-specific therapies and significant improvements in hemodynamics, echocardiography parameters of right ventricle function, 6-minute walk distance, and World Health Organization functional class.     

Pulmonary complications of portal hypertension: The overlooked decompensation

The systemic nature of cirrhosis and portal hypertension has long been recognized, and the amount of data characterizing the interplay between each system is becoming ever so complex. Lung involvement was among the first described associated entities in cirrhosis, with reports dating back to the late nineteenth century. However, it appears that throughout the years, interest in the pulmonary complications of portal hypertension has generally faded, especially in contrast to other decompensating events, as expertise in this field has primarily been concentrated in highly experienced tertiary care facilities and liver transplantation centers. Despite affecting up to 10%-15% of patients with advanced liver disease and having a proven prognostic impact, hepato-pulmonary syndrome, porto-pulmonary hypertension, and hepatic hydrothorax are frequently misdiagnosed, mistreated, or misinterpreted. This lack of precision might adversely impact patient care, referral to expert centers, and, ultimately, liver disease-related mortality and successful transplantation odds. The present minireview aims to increase awareness of the pulmonary complications of chronic liver disease by providing a brief overview of each of the three entities. The paper focuses on the essential theoretical aspects, addressing the most critical knowledge gaps on the one hand and, on the other hand, critically discussing one key issue for each complication.     

Critical care of the liver transplant patient: an update

The unique pathophysiology of patients with end-stage liver disease has important implications for their critical care treatment, particularly in the postoperative state. To gauge hemodynamic parameters and responses, each patient must be carefully evaluated for their place in the clinical spectrum of cirrhosis and portal hypertension. Although the data are limited, the biology of the consequences of liver disease is emphasized by novel treatments of hepatorenal syndrome, portopulmonary hypertension, and hepatopulmonary syndrome. These issues become more relevant with increased adult-to-adult living donor liver transplantation, in which technical considerations may further complicate the general treatment of the postoperative transplant patient.     

Surgical management of super-super obesity with grade III esophageal varices and liver cirrhosis: The ultimate challenge

The risk of complications after bariatric surgery is high in morbidly obese patients suffering from liver cirrhosis along with moderate to severe portal hypertension. Esophageal varices are even considered as a contraindication for bariatric surgery by many surgeons. We report the case of a 40-year-old gentleman with a body mass index of 65.3 kg/m², with multiple comorbidities including type 2 diabetes mellitus, severe obstructive sleep apnea. On evaluation, he had Child-Pugh A liver cirrhosis with portal hypertension along with grade III esophageal varices and splenomegaly. After adequate optimization, laparoscopic sleeve gastrectomy was performed. The patient is doing well at a follow up of 12 months with an adequate weight loss and resolution of comorbidities. Sleeve gastrectomy can be performed in a morbidly obese Child-Pugh A cirrhotic patient with portal hypertension and esophageal varices with proper counseling regarding more than usual risk for morbidity and mortality.     

Sonographic diagnosis and hemodynamic correlation in veno-occlusive disease of the liver

This study evaluated the role of duplex Doppler sonography in the diagnosis of VOD of the liver after bone marrow transplantation. Sixteen patients with clinical criteria of VOD were studied. The final diagnosis was achieved by transjugular liver biopsy, and the hepatic venous pressure gradient was measured during the procedure to estimate portal pressure. Nine patients (56.2%) had histologically proved VOD. Gallbladder wall thickening was present in 75% of patients with VOD, but in none of those without it (P = 0.01). Gallbladder wall thickening and ascites were present only in patients with portal hypertension. Nine patients (five with VOD and four without it) also were evaluated with duplex Doppler sonography, and no obvious flow abnormalities were detected in the portal vein and hepatic veins. These results suggest that sonography is useful in detecting early signs of portal hypertension pointing to the diagnosis of VOD in patients with bone marrow transplantation.     

The hyperdynamic circulation in cirrhosis: an overview

The hyperdynamic circulation begins in the portal venous bed as a consequence of portal hypertension due to the increased resistance to flow from altered hepatic vascular morphology of chronic liver disease. Dilatation of the portal vein is associated with increased blood flow, as well as the opening up or formation of veno-venous shunts and splenomegaly. At the same time, portal hypertension leads to subclinical sodium retention resulting in expansion of all body fluid compartments, including the systemic and central blood volumes. This blood volume expansion is associated with vasorelaxation, as manifested by suppression of the renin--angiotensin--aldosterone system, initially only when the patient is in the supine position. Acute volume depletion in such patients results in normalisation of the hyperdynamic circulation, whilst acute volume expansion results in exaggerated natriuresis. As liver disease progresses and liver function deteriorates, the systemic hyperdynamic circulation becomes more manifest with activation of the renin--angiotensin--aldosterone system. The presence of vasodilatation in the presence of highly elevated levels of circulating vasoconstrictors may be explained by vascular hyporesponsiveness due to increased levels of vasodilators such as nitric oxide, as well as the development of an autonomic neuropathy. However, vasodilatation is not generalised, but confined to certain vascular beds, such as the splanchnic and pulmonary beds. Even here, the status may change with the natural history of the disease, since even portal blood flow may decrease and become reversed with advanced disease. The failure of these changes to reverse following liver transplantation may be due to remodelling and angiogenesis.     

Cardiac tamponade in an orthotopic liver recipient with pulmonary hypertension

OBJECTIVE: To describe the clinical, hemodynamic, and echocardiographic findings of cardiac tamponade in a patient with portopulmonary hypertension shortly after orthotropic liver transplantation. DESIGN: Case report. SETTING: Surgical intensive care unit of a university teaching hospital. PATIENT: One patient with portopulmonary hypertension deteriorated progressively after orthotropic liver transplantation and developed cardiogenic shock. INTERVENTION: Serial transthoracic echocardiography showed increased right ventricular pressures and pericardial effusion without evidence of cardiac tamponade. Since right ventricular diastolic collapse may not be present in the setting of pulmonary hypertension and her clinical scenario was consistent with tamponade, pericardiocentesis was performed. MEASUREMENTS AND MAIN RESULTS: There was dramatic improvement of the clinical, hemodynamic, and echocardiographic variables after pericardiocentesis CONCLUSION: Pulmonary hypertension may decrease the predictive accuracy of echocardiographic clues for cardiac tamponade. Pericardiocentesis should be considered with clinical suspicion of cardiac tamponade without classic echocardiographic evidence in portopulmonary hypertension.     

原位辅助性部分肝移植治疗门静脉高压症的实验研究

目的 在原位辅助性部分肝移植(APOLT)动物模型基础上，观察其对猪肝硬化门静脉高压症的初步治疗效果。方法 采用结扎胆总管的方法复制猪胆汁性肝硬化动物模型，6只健康良种幼猪作为供体组，6只肝硬化模型猪为受体组，肝移植采用APOLT术。术中观察血流动力学和生化指标；术前、术后当天及7d观察门静脉压力、血胆红素及肝功能，同时用彩色多普勒超声检查门静脉最大流速及流量。结果 胆总管结扎8周后见肝脏假小叶形成，小叶周围结缔组织增生明显，有胆栓及胆泥沉积，证实胆汁性肝硬化模型成功。6只猪APOLT术后5只存活。术后7d动物活杀病理检查见移植肝形态、色泽正常，各吻合口无扭曲、漏血和血栓形成；移植肝部分肝小叶结构紊乱，肝细胞萎缩或消失，肝小叶内大量淋巴细胞和浆细胞浸润，中央静脉周围肝小叶细胞浊肿，可见淋巴细胞浸润；受体肝无明显变性及坏死。术后7d存活猪经彩色多普勒超声检察发现，移植肝门静脉血流比宿主肝门静脉血流增多，回流通畅，移植肝功能良好。血总胆红素、丙氨酸转氨酶及天冬氨酸转氨酶等肝功能指标明显好转，术后7d门静脉压力与术前相比显著降低。结论 APOLT术对门静脉高压症有一定的治疗作用，是一种较有希望的治疗肝硬化门静脉高压的新方法。     

肝肺综合征研究进展

肝肺综合征(hepato-pulmonary syndrome,HPS)是在慢性肝病和(或)门脉高压的基础上出现肺内血管异常扩张、气体交换障碍、动脉血氧合作用异常,导致低氧血症及一系列的病理生理变化和临床表现,是终末期肝脏病的严重肺部并发症。动物实验表明肺微血管扩张、血管新生和血管内单核巨噬细胞聚集是导致气体交换异常的主要原因,但具体机制仍不明确。目前HPS尚缺乏有效的治疗药物,肝移植仍是最有效的治疗方法。本研究将重点讨论HPS的发病机制和临床诊治相关的新进展。     

Current status and future of lung transplantation]

Lung transplantation has been performed successfully since 1983 in patients with various end-stage lung diseases including primary pulmonary hypertension. More than 10,000 lung transplants have been reported in The Registry of the International Society for Heart and Lung Transplantation. In contrast, a transplant law became effective in Japan only recently and 11 lung transplants have been performed with excellent results. We performed the first successful living-donor lobar lung transplantation for a 19-y-o-f with primary pulmonary hypertension on January 5, 2001 using her father's right lower lobe and her mother's left lower lobe. When the patients with primary pulmonary hypertension do not respond to prostacyclin therapy, lung transplantation is a workable option.     

肝肺综合征与气体信号分子

肝肺综合征是在慢性肝病、门静脉高压症的基础上,由多种因素共同参与、相互作用而导致低氧血症,肺血管扩张的一种疾病。肝肺综合征的发病机制较复杂且不完全明确,但气体信号分子参与了肺血管张力调节,并导致肺血管扩张。肝肺综合征预后差,严重威胁患者身体健康,积极有效地研究和防治肝肺综合征具有重要意义。本文就气体信号分子在肝肺综合征发病机制中的作用作一综述。     

Abnormally high resistive index of central retinal artery by ultrasound color Doppler in patients with viral chronic liver disease: correlation with worsening liver staging

Retrobulbar-ocular circulation provides an opportunity to assess the terminal circulation of the arterial cerebral tree. To evaluate whether retrobulbar circulation in patients with chronic liver disease is affected by adaptive mechanisms, we assessed by echo color Doppler, 1. The resistive-index of the central retinal artery, a terminal branch of the ophthalmic artery, and 2. the potential interrelationships with both liver staging and the most important splanchnic Doppler-parameters used to assess portal hypertension. The resistance index (RI) of the central retinal artery was obtained and compared with other classical Doppler parameters known to be affected by portal hypertension. The RI of the central retinal artery (CRA) was higher in cirrhotic patients than in controls or subjects with chronic hepatitis; it correlated with all the Doppler parameters of portal hypertension considered, with plasma renin-activity, and norepinephrine concentrations. Similarly to renal and splanchnic hemodynamics, retinal arterial circulation assessed by duplex Doppler seems to be affected by the histology of liver disease and by the overactivity of vasoconstrictor systems.