Hepatopulmonary syndrome.

The hepatopulmonary syndrom occurs when pulmonary microvacular dilatation causes hypoxemia in cirrhosis. It is found in between 15-20% of patients with chronic liver diseases and should be considered in the differential diagnosis of dyspnea or abnormal arterial oxygenation in this group. The presence of HPS appears to significantly increase mortality in affected patients with cirrhosis. The mediators of intrapulmonary vasodilatation and HPS are not fully characterized although pulmonary nitric oxide overproduction appears to be a key event in human and experimental models. Contrast echocardiography is the best screening test for pulmonary vasodilatation. Currently there are no effective medical therapies for HPS, although liver transplantation results in reversal of HPS in most cases. However, mortality is higher in patients with HPS undergoing transplantation relative to those without HPS.     

Hepatopulmonary syndrome: prevalence and clinical profile.

BACKGROUND: The hepatopulmonary syndrome (HPS) is defined as a triad of liver dysfunction, intrapulmonary vascular dilatations (IPVD) and arterial hypoxemia. There is paucity of Indian studies regarding the prevalence of IPVD and arterial hypoxemia particularly amongst patients with non-cirrhotic portal fibrosis (NCPF) and extrahepatic portal vein obstruction (EHPVO), where liver dysfunction is not a feature. METHODS: All patients with portal hypertension and esophageal varices seen at a tertiary care hospital during 1995-98 were studied. Ultrasonography of abdomen, contrast-enhanced echocardiography (CEE), arterial blood gas analysis and assessment of alveolar-arterial oxygen gradient were done. RESULTS: Of 138 patients with portal hypertension seen during the study period, 88 fulfilled the inclusion and exclusion criteria. These included 63 with cirrhosis, 15 with NCPF and 10 with EHPVO. CEE showed IPVD in 17 (27%) patients with cirrhosis, of which 11 (17.5%) fulfilled the criteria for HPS. IPVD were also noted in 4 (26.6%) cases of NCPF and 3 (30%) of EHPVO, though only 2 (13.3%) and 1 (10%) respectively had elevated alveolar-arterial gradient and liver dysfunction in addition. Age and sex distribution and duration of symptoms were not different in patients with HPS. Patients with HPS had higher incidence of dyspnea, platypnea, clubbing and spider nevi. CONCLUSIONS: Hepatopulmonary syndrome is present in 17.5% of cirrhotics, 13.3% of patients with NCPF and 10% with EHPVO. Patients with HPS had significantly higher incidence of dyspnea, platypnea, clubbing and spider nevi.     

Hepatopulmonary Syndrome

Hepatopulmonary syndrome (HPS) is a pulmonary complication observed in patients with chronic liver disease and/or portal hypertension, attributable to an intrapulmonary vascular dilatation that may induce severe hypoxemia. Microvascular dilation and angiogenesis in the lung have been identified as pathologic features that drive gas exchange abnormalities in experimental HPS. Pulse oximetry is a useful screening test for HPS, which can guide subsequent use of arterial blood gases. Contrast-enhanced echocardiography, perfusion lung scanning, and pulmonary arteriography are three currently used diagnostic imaging modalities that identify the presence of intrapulmonary vascular abnormalities. The presence of HPS increases mortality and impairs quality of life, but is reversible with liver transplantation. No medical therapy is established as effective for HPS. At the present time, liver transplantation is the only available treatment for HPS.     

Hepatopulmonary syndrome

Hepatopulmonary syndrome (HPS) is characterized by an oxygenation defect induced by pulmonary vascular dilatation in the setting of liver cirrhosis or portal hypertension. It is defined by an alveolar-arterial gradient > 15 mm Hg measured at sea level. This syndrome is seen in 15 to 30% of cirrhotic patients and has been associated with worse survival. Most HPS patients are either asymptomatic or develop the insidious onset of dyspnea. The key event in its pathogenesis is the development of intrapulmonary vascular dilatation (IPVD), which has been linked to increased pulmonary levels of nitric oxide. Pulse oximetry is a useful screening test for HPS, which can guide subsequent use of arterial blood gases. Contrast-enhanced transthoracic echocardiography is the most effective test to demonstrate IPVD. Another method for detecting IPVD is the radionuclide lung perfusion scanning, using technetium-labeled macroaggregated albumin particles. Liver transplantation is the only available treatment for HPS, resulting in complete resolution or significant improvement in gas exchange in over 85% of patients.     

A study of hepatopulmonary syndrome among patients of cirrhosis of liver and portal hypertension

OBJECTIVES: Hepatopulmonary syndrome consists of a triad of hepatic dysfunction and/or portal hypertension, intrapulmonary vascular dilatations and hypoxemia. A study of hepatopulmonary syndrome among patients of cirrhosis of liver and portal hypertension was undertaken. METHODS: Thirty patients participated in this study. The diagnosis of cirrhosis of liver was confirmed by liver biopsy. Arterial blood gas analysis, pulmonary function tests, two-dimensional transthoracic air contrast echocardiography were undertaken in all the patients. Those patients in whom contrast echocardiogram showed intrapulmonary vascular dilatations were classified as the positive group while others were labelled as the negative group. RESULTS: Ten patients (33.33%) had a positive contrast echocardiogram; five (16.67%) of them were found to have PaO2<70 mmHg and were qualified for the diagnosis of hepatopulmonary syndrome (HPS); and other five (16.67%) with PaO2>70 mmHg were diagnosed as intrapulmonary dilatations syndrome (IPVDS). Five patients of HPS revealed significant P(A-a)O2 gradient and intrapulmonary shunts of moderate severity computed by a/A ratio. Cyanosis (p=0.001), clubbing (p=0.009) and orthodeoxia (p=0.0024) were significantly commoner in the five patients of hepatopulmonary syndrome. Presence of spider naevi was significantly related with the presence of intrapulmonary vascular dilatations. CONCLUSIONS: The study results showed presence of hepatopulmonary syndrome and intrapulmonary vascular dilatation syndrome among patients of portal hypertension. The presence of cyanosis, clubbing and orthodeoxia were found to be suggestive indicators of hepatopulmonary syndrome. Even though not very specific, spider naevi were found to be a useful clinical indicator for the presence of intrapulmonary vascular dilatations.     

Portopulmonary Hypertension and Hepatopulmonary Syndrome: Is Transplant Always the Answer?

Portopulmonary hypertension (POPH) and hepatopulmonary syndrome (HPS) are two well-described liver–lung diseases. POPH is present in 5–10 % of patients with cirrhosis and is defined by the development of pulmonary arterial hypertension in the setting of portal hypertension. All patients who undergo a liver transplant (LT) evaluation are screened for this with a transthoracic echocardiogram, and if POPH is diagnosed, this may serve as a relative contraindication for a LT. If a patient with mild to moderate POPH responds to medical therapy, a LT may still be an option. HPS is more common affecting up to 30 % of patients with cirrhosis. These patients will have abnormal arterial oxygenation related to dilated intrapulmonary microvasculature. The development of HPS is an indication for a LT. Both of these conditions are recognized to increase morbidity and mortality, and a transplant center can apply for Model for End-Stage Liver Disease exception points in order to decrease a patient’s waitlist time.     

Hepatopulmonary syndrome and portopulmonary hypertension: what's new?

Hepatopulmonary syndrome (HPS) is found in 4-47% of patients with cirrhosis and is characterized by intrapulmonary vascular dilatations especially in the basal parts of the lung. Liver injury and/or portal hypertension trigger the release of endothelin-l, TNF-alpha, cytokines and mediate vascular shear stress and release of nitric oxide and carbon monoxide, all contributing to intrapulmonary vasodilation. Severe HPS increases mortality (30%) after liver transplantation, especially if Pa O2 is below 50 mmHg. The diagnosis is made by calculating the alveolar-arterial oxygen gradient and by performing a contrast echocardiography. Medical therapy fails and the only long-term treatment available is liver transplantation. More than 85% experience significant improvement or complete resolution in hypoxaemia, but this may take more than 1 year. Portopulmonary hypertension (PPHT) occurs in 2-8% of the patients with cirrhosis. Imbalance between vasodilating (decreased pulmonary expression of eNOS and prostacyclin I2) and vasoconstrictive agents (increased expression of ET-1 and angiotensin 1) may be responsible for misguided angiogenesis and pulmonary hypertension. The diagnosis is made by performing an echocardiography and a right heart catheterisation when systolic pulmonary artery pressure is higher than 30 mmHg on echocardiography. Although prostacyclin analogues are efficacious, adverse effects in terms of safety, tolerability and drug delivery occur. Bosentan is probably the therapy of choice for patients with PPHT because it decreases pulmonary but can also diminish portal hypertension. Sildenafil, a phosphodiesterase-5 inhibitor is used for idiopathic pulmonary hypertension, however, it should be used cautiously in patients with portal hypertension as it may increase portal hypertension by splanchnic vasodilation.     

Is there any medical therapeutic option in hepatopulmonary syndrome? A case report

Hepatopulmonary syndrome (HPS) is a well-known complication characterized by abnormalities of arterial oxygenation in patients with chronic liver disease, with or without portal hypertension. There is no definitive treatment for HPS except liver transplantation. We report on a patient with HBV-related liver cirrhosis and HPS who received garlic and lamivudine for 3 years. Signs of liver failure and hypoxemia gradually improved, indicating that lamivudine may improve the functional reserve of the liver, while garlic may help to reduce the signs and symptoms of HPS.     

Reversion of severe hepatopulmonary syndrome in a non cirrhotic patient after corticosteroid treatment for granulomatous hepatitis： A case report and review of the literature

Hepatopulmonary syndrome (HPS) is defined as a clinical triad including liver disease, abnormal pulmonary gas exchange and evidence of intrapulmonary vascular dilatations. We report a 61-year-old male presented with fatigue, long-lasting fever, loss of weight, signs of portal hypertension, hepatosplenomegaly, cholestasis and progressive dyspnoea over the last year. Clinical, laboratory and histological findings confirmed the diagnosis of granulomatous hepatitis. HPS due to hepatic granuloma-induced portal hypertension was proved to be the cause of severe hypoxemia of the patient as confirmed by contrast-enhanced echocardiography. Reversion of HPS after corticosteroid therapy was confirmed by a new contrast-enhanced echocardiography along with the normalization of cholestatic enzymes and improvement of the patient' s conditions. This is the first case of complete reversion of HPS in a non-cirrhotic patient with hepatic granuloma, indicating that intrapulmonary shunt in liver diseases is a functional phenomenon and HPS can be developed even in miscellaneous liver involvement as in this case.     

Review article: Update on current and emergent data on hepatopulmonary syndrome

Hepatopulmonary syndrome(HPS) is a frequent pulmonary complication of end-stage liver disease, characterized by impaired arterial oxygenation induced by intrapulmonary vascular dilatation. Its prevalence ranges from 4% to 47% in patients with cirrhosis due to the different diagnostic criteria applied among different studies. Nitric oxide overproduction and angiogenesis seem to be the hallmarks of a complicated pathogenetic mechanism, leading to intrapulmonary shunting and ventilation-perfusion mismatch. A classification of HPS according to the severity of hypoxemia has been suggested. Contrast-enhanced echocardiography represents the gold standard method for the detection of intrapulmonary vascular dilatations which is required, in combination with an elevated alveolar arterial gradient to set the diagnosis. The only effective treatment which can modify the syndrome's natural history is liver transplantation. Although it is usually asymptomatic, HPS imparts a high risk of pretransplantation mortality, independently of the severity of liver disease, while there is variable data concerning survival rates after liver transplantation. The potential of myocardial involvement in the setting of HPS has also gained increasing interest in recent research. The aim of this review is to critically approach the existing literature of HPS and emphasizeunclear points that remain to be unraveled by future research.     

肝肺综合征的诊治对策

肝肺综合征(HPS)是肝病和/或门静脉高压患者常见的肺部并发症,其特征表现为肺内血管扩张引起的动脉氧合异常。HPS发病机制复杂,临床上早期诊断率低,预后差。目前HPS尚缺乏有效治疗药物,肝移植是唯一根本治疗手段。现就HPS发病机制、临床表现、诊断及治疗进行概述,旨在进一步提高临床筛查和诊治HPS的水平。     

A severe (type II) hepatopulmonary syndrome in a patient with idiopathic portal hypertension and treatment with paroxetine

The hepatopulmonary syndrome has been defined as chronic liver disease accompanied by abnormal pulmonary gas exchange, which might result in arterial deoxygenation, and widespread intrapulmonary vasodilation. Although it has been pointed out that hepatopulmonary syndrome occurs in liver cirrhosis, there are a few studies in the literature reporting noncirrhotic portal hypertension as a cause of hepatopulmonary syndrome. Currently, liver transplantation is the only effective therapy for such patients. on the other hand, there is also a proposal about considering paroxetine, a potent nitric oxide synthase inhibitor, for use in the hepatopulmonary syndrome. We present a patient with severe (type II) hepatopulmonary syndrome caused by idiopathic portal hypertension and discuss the consequences of paroxetine therapy.     

Hepatopulmonary syndrome

Hepatopulmonary syndrome is caused by intrapulmonary vasodilation that leads to abnormal arterial gas exchange in the setting of liver disease or portal hypertension. It is seen in up to 15% of cirrhotics and is an increasingly common indication for liver transplantation. Testing for the presence of oxygenation abnormalities and intrapulmonary vasodilation is needed to make the diagnosis. Excess production of nitric oxide in the lung contributes to pulmonary vasodilation and may be triggered by the release of mediators from the damaged liver. No medical therapies are established as effective, and liver transplantation is the only documented curative treatment.     

Prevalence of hepatopulmonary syndrome in cirrhosis and extrahepatic portal venous obstruction

OBJECTIVE: Hepatopulmonary syndrome (HPS) is characterized by arterial hypoxemia in patients with chronic liver disease caused by abnormal intrapulmonary vasodilations. Data on its frequency vary from 5% to 29%. Most of these studies are from the West and in patients with cirrhosis. We, therefore, studied the prevalence of HPS in patients with liver cirrhosis and extrahepatic portal venous obstruction (EHPVO). METHODS: We studied 54 consecutive patients with liver cirrhosis (42 men and 12 women; mean age = 44.2 +/- 13 yr; Child grade A: 13, B: 22, and C: 19) and 50 patients with EHPVO (31 men and 19 women; mean age = 23.3 +/- 7.8 yr) Diagnosis of cirrhosis was made by history, liver function abnormalities, endoscopy, and sonography, whereas EHPVO was diagnosed by demonstration of a block in the splenoportovenous axis on sonography. Each of the patients underwent chest x-ray, arterial blood gas analysis, contrast-enhanced echocardiography (CEE), and pulmonary function tests. HPS was diagnosed in a patient with positive CEE, in the presence of hypoxia (PaO2 < 70 mm Hg) and/or elevated alveolar arterial oxygen gradient of > 20 mm Hg in the absence of any underlying cardiopulmonary disease. RESULTS: Ten of 54 patients (18.5%) with cirrhosis were positive on CEE compared with two of 50 patients (4%) with EHPVO. Six of the 10 patients positive with cirrhosis for CEE had associated hypoxia, whereas only one EHPVO patient with positive CEE had an elevated pulmonary alveolar arterial oxygen gradient of > 20 mm Hg. Thus, the incidence of HPS was 11.1% in patients with cirrhosis, compared with 2% in patients with EHPVO. One patient with HPS and cirrhosis had clinical cyanosis. CONCLUSION: HPS occurs more commonly in patients with cirrhosis but can also be seen in patients with EHPVO.     

Cirrhosis and hepatopulmonary syndrome

Hepatopulmonary syndrome(HPS)is characterized as a triad:liver disease,intrapulmonary vascular dilatation and arterial hypoxemia.HPS is reported to be present in 4%to 32%of adult patients with end-stage liver disease and in 9%-20%of children.The pathogenesis of HPS has not been clearly identified.Portal hypertension causes impairment in the perfusion of the bowel and increases the enteral translocation of Gram(-)bacteria and endotoxins.This stimulates the release of vasoactive mediators,such as tumor necrosis factor-alpha,heme oxygenase-derived carbon monoxide and nitric oxide.Genetic alterations have not been associated with this syndrome yet;however,cytokines and chemokines have been suggested to play a role.Recently,it was reported that cumulated monocytes lead to the activation of vascular endothelial growth factor-dependent signaling pathways and pulmonary angiogenesis,which plays an important role in HPS pathogenesis.At present,the most effective and only radical treatment is a liver transplant(LT).Cirrhotic patients who are on the waiting list for an LT have a shorter survival period if they develop HPS.Therefore,it is suggested that all cirrhotic cases should be followed closely for HPS and they should have priority in the waiting list.     

Pulmonary vascular abnormalities in cirrhosis

Two pulmonary vascular disorders can occur in liver disease and/or portal hypertension: the hepatopulmonary syndrome (HPS), which is characterized by intrapulmonary vascular dilatations, and portopulmonary hypertension (POPH), in which pulmonary vascular resistance is elevated. POPH and HPS are characterized by distinct pulmonary microvascular remodelling, which occurs at different anatomical sites of the pulmonary microcirculation. The exact pathophysiological mechanisms of these pulmonary vascular disorders are unknown. However, as HPS and POPH have been reported in patients with extrahepatic portal hypertension, the factor that determines their development must be portal hypertension. The clinical presentations are very different, with gas exchange impairment in HPS and hemodynamic failure in POPH. The severity of HPS seems to parallel the severity of liver failure, whereas no simple relationship has been identified between hepatic impairment and the severity of POPH. Resolution of HPS is common after liver transplantation, which has an uncertain effect in POPH.     

Hepatopulmonary syndrome

Opinion statement The hepatopulmonary syndrome (HPS) is an important and often under-recognized vascular complication of cirrhosis and portal hypertension characterized by pulmonary vascular dilatation, which results in hypoxemia. This syndrome is identified in as many as 20% of patients who are evaluated for orthotopic liver transplantation (OLT), and it has recently been found to increase mortality in affected patients, particularly when hypoxemia is severe. Currently, OLT is the only therapy established to reverse intrapulmonary vasodilatation, although postoperative mortality is increased in patients with severe hypoxemia. No randomized controlled trials of pharmacologic therapies have been undertaken, but supplemental oxygen improves oxygenation. Data derived from case reports, small studies, and experimental models suggest that pharmacologic therapies may be effective. In cirrhotic patients with HPS, particularly those with moderate hypoxemia (PaO2 < 60 mmHg), OLT should be considered prior to the development of severe deoxygenation. Supplemental oxygen should be given to patients with a PaO2 < 60 mmHg or those with exercise oxygen desaturation. For those patients with mild hypoxemia or those who are not OLT candidates, a trial of pharmacologic treatment may be considered.     

Prospective evaluation of outcomes and predictors of mortality in patients with hepatopulmonary syndrome undergoing liver transplantation

The hepatopulmonary syndrome (HPS) occurs in a subgroup of patients with cirrhosis and results from intrapulmonary vasodilatation, which may cause significant hypoxemia. Liver transplantation has emerged as a therapeutic option for patients with HPS based on retrospective case series and reports. However, morbidity and mortality appear to be increased after transplantation for HPS, and no prospective studies evaluating clinical features that may predict poor surgical outcome are available. Therefore, we prospectively evaluated the utility of the degree of hypoxemia, the arterial oxygen response to 100% oxygen administration, and the macroaggregated albumin (MAA) scan quantification of intrapulmonary shunting as predictors for outcome after liver transplantation. Our cohort consisted of 24 patients with cirrhosis and HPS who underwent liver transplantation over a 5-year period at 2 transplant centers who were followed at least 1 year after transplantation. All patients underwent preoperative evaluation for HPS with standardized methods. Seven patients (29%) died postoperatively, 5 of cardiorespiratory complications. All deaths occurred within 10 weeks after transplantation. A preoperative arterial oxygen tension (PaO(2)) of /= 20% were the strongest predictors of postoperative mortality. In conclusion, we found that mortality is increased after liver transplantation for HPS, particularly in patients with more severe hypoxemia and significant intrapulmonary shunting. Preoperative testing for the severity of HPS can be used to stratify patients according to the risk for postoperative mortality.     

Analysis of pulmonary heme oxygenase-1 and nitric oxide synthase alterations in experimental hepatopulmonary syndrome

BACKGROUND & AIMS: Cirrhosis and portal hypertension due to chronic common bile duct ligation reproduce the features of human hepatopulmonary syndrome, whereas portal hypertension alone due to partial portal vein ligation does not. Nitric oxide contributes to experimental hepatopulmonary syndrome, but the nitric oxide synthase forms involved remain controversial. Recently, increased pulmonary heme oxygenase-1 expression and carbon monoxide production have also been found after common bile duct ligation. Our aim was to explore the role of the heme oxygenase-1/carbon monoxide pathway in the pathogenesis of experimental hepatopulmonary syndrome. METHODS: Pulmonary heme oxygenase-1 expression and distribution were assessed in sham; 3-week partial portal vein ligation; and 1-, 2-, 3-, 4-, and 5-week common bile duct ligation animals by Northern, Western and immunohistochemical analysis relative to endothelial and inducible nitric oxide synthase levels and to hepatopulmonary syndrome development. In vivo heme oxygenase enzyme inhibition with tin protoporphyrin IX in common bile duct ligation animals was used to define effects on intrapulmonary vasodilatation and arterial blood gases. RESULTS: Heme oxygenase-1 expression in pulmonary intravascular monocytes/macrophages and arterial carboxyhemoglobin levels increased progressively from 3 to 5 weeks after common bile duct ligation relative to controls (5-week protein levels were 15.94 +/- 1.75-fold those of sham animals; P < 0.001). Inducible nitric oxide synthase increased transiently in pulmonary intravascular monocytes/macrophages in 3-week common bile duct ligation animals, whereas pulmonary microvascular endothelial nitric oxide synthase increases began at 2 weeks and correlated with the onset of hepatopulmonary syndrome. Tin protoporphyrin treatment normalized carboxyhemoglobin and improved arterial blood gases and intrapulmonary vasodilatation, reflecting partial reversal of hepatopulmonary syndrome. CONCLUSIONS: The heme oxygenase-1/carbon monoxide system is an important contributor to the progression of experimental hepatopulmonary syndrome in addition to alterations in the endothelial nitric oxide synthase/nitric oxide pathway.     

The hepatopulmonary syndrome

The hepatopulmonary syndrome occurs in subjects with chronic liver disease and/or portal hypertension who develop intrapulmonary vasodilation resulting in arterial deoxygenation. Clinical and basic science studies investigating the pathophysiology of HPS are presented. A diagnostic algorithm is provided using contrast echocardiography, the lung perfusion scan, and pulmonary angiography. Medical therapy and experience with liver transplantation are reviewed.