Portopulmonary hypertension

Portopulmonary hypertension (PPHT) is a respiratory complication of portal hypertension, defined as an increase in mean pulmonary artery pressure (PAP) of > 25 mmHg with an increase in pulmonary vascular resistance of > 240 dyn.s/cm(-5) and a normal pulmonary capillary wedge pressure ( < 15 mmHg), which often occurs in subjects with liver cirrhosis. Histopathological features of PPHT are endothelial and smooth-muscle cell proliferation and fibrosis leading to luminal obstruction in the resistance arteries. The pathogenesis of PPHT may result from an imbalance between vasoconstrictor and vasodilating factors. The most common pulmonary symptom is exertional dyspnea; fatigue, chest pain and syncope occur more often at an advanced stage. Edema, ascites and prominent jugular veins are signs of both decompensated hepatic cirrhosis and right ventricular failure. Right heart catheterisation is the gold standard for the diagnosis and defines PPHT in mild disease with PAP less than 35 mmHg, moderate disease with PAP between 35 and 45 mmHg, and severe disease with PAP of 45 mmHg or higher. The medical treatment of portopulmonary hypertension is based on the treatment of other forms of pulmonary arterial hypertension, including vasomodulating pharmacologic agents. Liver transplantation is accompanied by high risk of mortality, generally due to acute right ventricular failure and cardiovascular collapse. The prognosis of PPHT is poor with mean survival of 15 months.     

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.     

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.     

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.     

Place de la réanimation chez le cirrhotique

In cirrhotic patients, liver insufficiency and portal hypertension represent a source of potentially life threatening complications, which may justify intensive care. In addition to specific complications (variceal bleeding, hepatic encephalopathy and hepatorenal syndrome), cirrhosis is a condition which favors non-specific complications including severe bacterial infections and acute renal failure. Apart from these complications, cirrhosis is constantly associated with dysfunctions of several organs and systems (cardiocirculatory system, respiratory system, central nervous system, immune system and coagulation). When severe complications occur, dysfunctions of these organs and system can progress and lead to multi-organ failure. As a result, the prognosis of cirrhotics in intensive care units is poor. A major issue is to determine which patients should be admitted to intensive care. Different prognostic scores have been proposed but none is perfect. Practically, admission in an intensive care unit is justified in the absence of significant hepatic insufficiency or when hepatic insufficiency is reversible, when liver transplantation is possible, and in case of iatrogenic complications. In other conditions, mortality is close to 100% and intensive care may not be justified. Theoretically, the correction of hepatic insufficiency could help to improve the results of intensive care in cirrhotic patients. The tolerance and efficacy of artificial liver support systems (albumin dialysis and bioartificial liver) remain unclear. However, these systems offer attractive perspectives.     

Failure of hypoxic pulmonary vasoconstriction in patients with liver cirrhosis

The combination of arterial hypoxemia and low pulmonary vascular resistance in patients with liver cirrhosis is unexplained. Pulmonary microcirculatory dilation, but not gross arterio-venous shunts, has been the usual postmortem finding in patients with liver cirrhosis. When 10 patients with alcoholic liver cirrhosis breathed 10% oxygen in nitrogen, they failed to increase their pulmonary vascular resistance. However, four patients with functional murmurs, three patients with hyperkinetic heart syndrome, six patients with normal pulmonary artery pressures and intracardiac left to right shunts, and five patients with renal failure and anemia all increased their pulmonary vascular resistances when they breathed 10% oxygen in nitrogen. These findings suggested that in liver cirrhosis the normal regulating mechanism (hypoxic vasoconstriction) of the pulmonary circulation may be impaired, resulting in failure of the lung to match perfusion with ventilation.     

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.     

Pathogenesis, diagnosis, and treatment of alcoholic liver disease

Alcohol-related liver disease is a major cause of morbidity and mortality in the United States. Alcoholic liver disease encompasses a clinicohistological spectrum, including fatty liver, alcoholic hepatitis, and alcoholic cirrhosis. Fatty liver is a benign and reversible condition, but progression to alcoholic hepatitis and cirrhosis is life-threatening. Alcoholic hepatitis is diagnosed predominantly on clinical history, physical examination, and laboratory testing, although liver biopsy is often necessary to secure the diagnosis. The major focus of management is abstinence from alcohol, supportive care, treatment of complications of infection and portal hypertension, and maintenance of positive nitrogen balance through nutritional support. Corticosteroid therapy is controversial but should be considered in patients with a discriminant function greater than 32 and/or presence of spontaneous hepatic encephalopathy in the absence of infection, gastrointestinal bleeding, and renal failure. The only curative therapy for advanced alcoholic cirrhosis is liver transplantation. Several recent advances in understanding the pathogenesis of alcoholic liver disease may lead to novel future treatment approaches, including inhibition of tumor necrosis factor a, antioxidant therapy, stimulation of liver regeneration, and stimulation of collagen degradation.     

Hepatopulmonary syndrome-attributed extreme hypoxemia and polycythemia revealing liver cirrhosis

We report an unusual case of severe hepatopulmonary syndrome with previously unrecognized cirrhosis, presenting with acute on chronic dyspnoea, extreme hypoxemia, secondary polycythemia as well as direct identification of arteriovenous communications on computed tomography angiography. Hepatopulmonary syndrome, defined as the combination of hepatopathy, arterial deoxygenation and pulmonary vascular dilatation, is increasingly recognized as a life-threatening complication in advanced liver disease and transplant candidacy. It is usually diagnosed in chronic liver disease patients following pre-transplant evaluation or mild dyspnea investigation. Diagnosis relies on the indirect evidence of pulmonary arteriovenous communications suggested by echocardiography with a bubble study. Clinicians need to be aware of this rare but potential acute presentation at the emergency room.     

Intensive care of patients with acute liver failure: recommendations of the U.S. Acute Liver Failure Study Group

OBJECTIVE: To provide a uniform platform from which to study acute liver failure, the U.S. Acute Liver Failure Study Group has sought to standardize the management of patients with acute liver failure within participating centers. METHODS: In areas where consensus could not be reached because of divergent practices and a paucity of studies in acute liver failure patients, additional information was gleaned from the intensive care literature and literature on the management of intracranial hypertension in non-acute liver failure patients. Experts in diverse fields were included in the development of a standard study-wide management protocol. MEASUREMENTS AND MAIN RESULTS: Intracranial pressure monitoring is recommended in patients with advanced hepatic encephalopathy who are awaiting orthotopic liver transplantation. At an intracranial pressure of > or =25 mm Hg, osmotic therapy should be instituted with intravenous mannitol boluses. Patients with acute liver failure should be maintained in a mildly hyperosmotic state to minimize cerebral edema. Accordingly, serum sodium should be maintained at least within high normal limits, but hypertonic saline administered to 145-155 mmol/L may be considered in patients with intracranial hypertension refractory to mannitol. Data are insufficient to recommend further therapy in patients who fail osmotherapy, although the induction of moderate hypothermia appears to be promising as a bridge to orthotopic liver transplantation. Empirical broad-spectrum antibiotics should be administered to any patient with acute liver failure who develops signs of the systemic inflammatory response syndrome, or unexplained progression to higher grades of encephalopathy. Other recommendations encompassing specific hematologic, renal, pulmonary, and endocrine complications of acute liver failure patients are provided, including their management during and after orthotopic liver transplantation. CONCLUSIONS: The present consensus details the intensive care management of patients with acute liver failure. Such guidelines may be useful not only for the management of individual patients with acute liver failure, but also to improve the uniformity of practices across academic centers for the purpose of collaborative studies.     

Hepatopulmonary syndrome.

The hepatopulmonary syndrome (HPS) is a rare complication of liver cirrhosis and is characterised by the typical triad of liver cirrhosis, arterial hypoxemia, and intrapulmonary vascular dilatation. Except for pleural effusions associated with liver cirrhosis no other disease of the lungs or the heart is detectable. The structural hallmark of HPS is dilatation of pulmonary precapillary vessels which impairs diffusion-perfusion and causes unequal ventilation-perfusion. The diagnosis of HPS is based on PaO2 measurements when breathing room air and 100% oxygen. The increased intrapulmonary vascular diameter allows microbubbles to traverse the lung capillaries when agitated saline is administered intravenously. Only on rare occasions is a patient limited by his pulmonary impairment, the leading morbidity is that of liver disease and its classical complications. Drug therapy is of no proven benefit, oxygen supplementation might improve dyspnea. Vascular embolisation of discrete arteriovenous shunts, if present, or liver transplantation may dramatically improve pulmonary function in selected patients.     

Current management approaches to portopulmonary hypertension

Portopulmonary hypertension (PoPH) is a rare but life-threatening complication of portal hypertension that is characterised by proliferative changes in the pulmonary microvasculature indistinguishable from other forms of pulmonary arterial hypertension (PAH). Although PoPH is most commonly observed in the setting of cirrhosis, patients with non-cirrhotic portal hypertension are also at risk of developing the disorder. A definitive diagnosis requires invasive haemodynamic confirmation by right heart catheterisation and screening for PoPH should be routinely performed in all patients being considered for liver transplantation. Although severe PoPH is considered a contraindication to liver transplantation, there is now compelling data supporting the use of PAH-specific therapies with the aim of improving pulmonary haemodynamics to allow transplantation to be successfully performed. This review explores possible relevant aetiological factors and summarises current diagnostic and therapeutic approaches for PoPH patients.     

急性肝功能衰竭急诊肝移植围术期治疗的单中心经验探讨

背景：急性肝衰竭行急诊肝移植患者围手术期治疗的病情复杂,风险大,并发症多,死亡率高,与普通肝脏移植有着明显不同。目的：总结急诊肝移植治疗急性肝功能衰竭的围手术期治疗经验,以提高急性肝功能衰竭的治疗成功率。方法：回顾性分析38例因急性肝功能衰竭行急诊肝移植患者的临床资料,男21例,女17例,年龄15-69岁。其中乙型肝炎病毒性肝炎23例（其中乙型合并丁型肝炎2例）,Wilsons病7例,3例为毒蕈中毒,2例不明原因药物肝脏损害,1例雷公藤多甙中毒,1例为外伤行肝脏部分切除后失代偿,1例尸体肝移植后患者。结果与结论：38例患者生存时间为13-1740d,中位生存时间为634d。患者的围手术期存活率为76%,1年存活率为63%,2年存活率为58%。9例围手术期死亡原因包括脑水肿及颅内高压、肾功能衰竭、严重肺部感染、多脏器功能衰竭、凝血功能障碍（颅内出血、上消化道出血等）、急性成人呼吸窘迫综合征、移植物原发性无功能。目前急诊肝移植仍是治疗急性肝功能衰竭最有效的方法,出血、感染、排异反应是死亡的主要原因,肝移植围手术期间每一环节的处理,对于肝移植的成功和患者长期存活具有重要意义。     

Hypercoagulation and thrombophilia in liver disease.

A complex balance exists between endogenous procoagulants and the anticoagulant system in liver disease patients. Hypercoagulable events occur in cirrhosis patients despite the well-known bleeding diathesis of liver disease. These events may be clinically evident, such as in portal vein thrombosis or pulmonary embolism, but these conditions may also be a silent contributor to certain disease states, such as portopulmonary hypertension or parenchymal extinction with liver atrophy as well as thrombosis of extracorporeal circuits in dialysis or liver assist devices. Moreover, liver disease-related hypercoagulability may contribute to vascular disease in the increasingly common condition of non-alcoholic fatty liver disease. Despite the incidence of these problems, there are few widely accessible and practical laboratory tests to evaluate the risk of a hypercoagulable event in cirrhosis patients. Furthermore, there is little research on the use of commonly accepted anticoagulants in patients with liver disease. This article is a result of an international symposium on coagulation disorders in liver disease and addresses several areas of specific interest in hypercoagulation in liver disease. Critical areas lacking clinical information are highlighted and future areas of research interest are defined with an aim to foster clinical research in this field.     

超声造影对肝移植患者术前肾功能评估的初步应用

目的探讨超声造影对肝移植患者术前肾功能评价的应用价值。方法对我院76例肝移植患者行术前肾脏超声造影检查,包括肝硬化代偿期患者25例,肝硬化失代偿期患者36例,肝肾综合症患者15例;正常对照组28例。造影剂为SonoVue,用ACQ软件对造影图像中皮质部位进行分析,观察指标为造影剂到达时间(AT)、达峰时间(TTP)及达峰强度(PI)。结果各项观察指标在肝硬化代偿组与正常对照组无明显差异(P>0.05);肝硬化失代偿期组患者TTP较正常组及肝硬化代偿组明显延长,PI明显降低(P<0.05);肝肾综合征组AT、TTP较肝硬化失代偿组进一步延长,PI进一步降低(P<0.05)。结论超声造影有助于肝移植术前肝硬化患者肾功能评价。     

二维彩色多普勒超声观测肝硬化门脉高压症脾肺固定合并门奇断流术前后门脉系统血流动力学改变

本文应用二维彩色多普勒超声对8例肝硬化门脉高压症的门脉系统血流动力学在脾肺固定合并门奇断流术前后分别进行定量研究和对比分析。结果表明术后门静脉及睥静脉的内径、平均流速和血流量比术前明显缩小和降低(P<0.001～0.05),门、睥静脉的血流量减少,两者呈正向相关关系(r=0.93,p<0.001)。结果认为该手术能使门静脉系统发生断流、分流和减流.使门静脉系统血流量减少,门脉高压及脾胃区高压缓解。双功能超声对门脉高压症手术方法的选择及效果的评价是一种有临床应用价值的无创性检查方法。     

Diagnosis and treatment of pulmonary hypertension

Primary pulmonary hypertension is a rare disease of unknown etiology, whereas secondary pulmonary hypertension is a complication of many pulmonary, cardiac and extrathoracic conditions. Chronic obstructive pulmonary disease, left ventricular dysfunction and disorders associated with hypoxemia frequently result in pulmonary hypertension. Regardless of the etiology, unrelieved pulmonary hypertension can lead to right-sided heart failure. Signs and symptoms of pulmonary hypertension are often subtle and nonspecific. The diagnosis should be suspected in patients with increasing dyspnea on exertion and a known cause of pulmonary hypertension. Two-dimensional echocardiography with Doppler flow studies is the most useful imaging modality in patients with suspected pulmonary hypertension. If pulmonary hypertension is present, further evaluation may include assessment of oxygenation, pulmonary function testing, high-resolution computed tomography of the chest, ventilation-perfusion lung scanning and cardiac catheterization. Treatment with a continuous intravenous infusion of prostacyclin improves exercise capacity, quality of life, hemodynamics and long-term survival in patients with primary pulmonary hypertension. Management of secondary pulmonary hypertension includes correction of the underlying cause and reversal of hypoxemia. Lung transplantation remains an option for selected patients with pulmonary hypertension that does not respond to medical management.     

肾脏动静脉通过时间在肝移植术前肾功能评估中的应用

目的 探讨超声造影检测肾脏动静脉通过时间(RAVIT)对肝移植患者术前肾功能评价的应用价值.方法 对我院102例肝移植患者术前行肾脏超声造影检查,据临床症状分为肝硬化代偿期组、肝硬化失代偿期组和肝肾综合征组;选取健康人45例为对照组.造影后对肾门处肾动静脉主干内造影剂到达时间(AT)进行测定和差值分析.结果 肾动脉到达时间(BAAT)、肾静脉到达时间(RVAT)及RAVIT在肝硬化代偿期组和对照组间无明显差异(P＞0.05);肝硬化失代偿期组RATT、RVIT及RAVTT较肝硬化失代偿期组和对照组延长(P＜0.05);肝肾综合征组RATT、RVIT、RAVIT在4组中最长(P＜0.05).结论 RATT、RVTT及RAVTT可作为评价肝移植患者术前肾功能的参考指标.     

Cirrhosis and chronic liver failure: part II. Complications and treatment

Major complications of cirrhosis include ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, portal hypertension, variceal bleeding, and hepatorenal syndrome. Diagnostic studies on ascitic fluid should include a differential leukocyte count, total protein level, a serum-ascites albumin gradient, and fluid cultures. Therapy consists of sodium restriction, diuretics, and complete abstention from alcohol. Patients with ascitic fluid polymorphonuclear leukocyte counts of 250 cells per mm3 or greater should receive empiric prophylaxis against spontaneous bacterial peritonitis with cefotaxime and albumin. Patients who survive an episode of spontaneous bacterial peritonitis should receive long-term prophylaxis with norfloxacin or trimethoprim/sulfamethoxazole. Patients with gastrointestinal hemorrhage and cirrhosis should receive norfloxacin or trimethoprim/sulfamethoxazole twice daily for seven days. Treatment of hepatic encephalopathy is directed toward improving mental status levels with lactulose; protein restriction is no longer recommended. Patients with cirrhosis and evidence of gastrointestinal bleeding should undergo upper endoscopy to evaluate for varices. Endoscopic banding is the standard treatment, but sclerotherapy with vasoconstrictors (e.g., octreotide) also may be used. Prophylaxis with propranolol is recommended in patients with cirrhosis once varices have been identified. Transjugular intrahepatic portosystemic shunt has been effective in reducing portal hypertension and improving symptoms of hepatorenal syndrome, and can reduce gastrointestinal bleeding in patients with refractory variceal hemorrhage. When medical therapy for treatment of cirrhosis has failed, liver transplantation should be considered. Survival rates in transplant recipients have improved as a result of advances in immunosuppression and proper risk stratification using the Model for End-Stage Liver Disease and Child-Turcotte-Pugh scoring systems.