23例肝肺综合征临床分析

探讨肝肺综合征(HPS)的临床特点和预后。67例肝硬化患者均应用血气分析仪测定其动脉血氧分压(PaO2),其中Ch ild-Pugh分级A级30例,B级22例,C级15例。67例肝硬化患者中23例合并HPS,发病率为34.3%。其发病率与Ch ild-Pugh分级有关,与A级比较C级HPS,发病率显著增高(P<0.05);门静脉增宽与不宽者、胃底食管静脉曲张与未发现曲张者、有蜘蛛痣与无蜘蛛痣者分别合并有HPS,两者比较均差异有显著性(P<0.05)。23例HPS患者中7例死亡,HPS均不是直接死亡原因。有门脉高压、蜘蛛痣时提示HPS的存在。早期诊断和治疗有助于缓解低氧血症,改善预后。     

Progress in investigating the pathogenesis of hepatopulmonary syndrome

BACKGROUND: The pathogenesis of hepatopulmonary syndrome is complicated and remains unknown. This review aims to provide an updated knowledge about the pathogenesis of the syndrome. DATA SOURCES: Five medical databases, MEDLINE, Science-Direct, OVID, Springer Link, and Wiley InterScience were searched for articles on hepatopulmonary syndrome, cirrhosis, angiogenesis, intestinal endotoxemia, nitric oxide, carbon monoxide, and other related subjects. RESULTS: Currently, imbalance between vasodilation and vaso...     

Clinical and haemodynamic aspects of hepatopulmonary syndrome in Indian patients with cirrhosis

BACKGROUND: Hepatopulmonary syndrome consists of the triad of hepatic dysfunction and/or portal hypertension, intrapulmonary vascular dilatation and hypoxaemia, in the absence of detectable primary cardiopulmonary diseases. In the present study, we examined the frequency of hepatopulmonary syndrome among Indian patients with cirrhosis, and studied clinical predictors and pulmonary haemodynamic alterations. METHODS: Forty-five patients with cirrhosis and no cardiopulmonary diseases were investigated by air-contrast echocardiography. Where patients were positive, arterial blood gas analysis was carried out. Positive contrast echocardiography with PO2 < 70 mmHg confirmed the diagnosis of hepatopulmonary syndrome. Three cases with the syndrome and 24 without were assessed for haemodynamic status by hepatic and pulmonary catheterization. RESULTS: Four of 45 cases of cirrhosis (8.9%) had positive contrast echocardiographies, including three (6.7%) with hepatopulmonary syndrome and one 'subclinical' case (positive contrast echocardiography without hypoxaemia). Under haemodynamic study, the mean pulmonary arterial and pulmonary capillary wedge pressures appeared to be lower among those patients with hepatopulmonary syndrome. CONCLUSIONS: In this small study, the frequency of hepatopulmonary syndrome was relatively low (6.7%). Cyanosis was the only reliable clinical indicator, and there was no clear relationship with the severity of cirrhosis by Child's grading.     

Expression of endothelial cell adhesion molecules in neovascularized tissue

OBJECTIVE: Recent studies indicate that endothelial cells of newly formed blood vessels are activated and exhibit a distinct phenotype that may influence the responses of these microvessels to an inflammatory stimulus. The objective of this study was to compare the basal and cytokine-stimulated expression of endothelial cell adhesion molecules in neovascularized tissue to normal (nonproliferating) vascular beds. METHODS: The expression of P- and E-selectin. VCAM-1, ICAM-1, ICAM-2, and PECAM-1 was measured, using the dual radiolabeled mAb technique, in subcutaneously implanted (for 10-15 days) polyurethane sponges, skin, heart, lung, and intestine of male C57BL/6 mlice (background). RESULTS: Basal values of PECAM-1 and ICAM-2 revealed a low vascular density in the implanted sponge matrices that is comparable to skin. When normalized for vascular surface area (PECAM-1 or ICAM-1 expression), the basal level of E- and P-selectin expression was highest in neovascularized sponge and skin. TNF-alpha elicited an increased expression of all endothelial CAMs, except PECAM-1 and ICAM-2, but the responses were blunted in sponge and skin, relative to other vascular beds. CONCLUSIONS: These findings indicate that endothelial cells in newly formed blood vessels exhibit a pattern of basal and cytokine-induced expression of certain adhesion glycoproteins that is similar to nonproliferating cutaneous vessels.     

Two cases of hepatopulmonary syndrome with improved liver function following long-term oxygen therapy

Hepatopulmonary syndrome (HPS) is a complication of liver disease that is characterized by hypoxemia and intrapulmonary vascular dilatations. The only established therapy for this disorder is liver transplantation. Here, we report two patients (a 63-year-old woman and a 72-year-old man) with HPS associated with hepatitis C virus-related cirrhosis. We gave the patients low-dose oxygen supplementation to improve their respiratory symptoms. Surprisingly, their liver function improved from Child Pugh class C to class A, and ascites disappeared after a year of oxygen supplementation. We believe that long-term oxygen therapy contributed to the improvement of liver function in these two cases. Long-term oxygen therapy might offer a new therapeutic approach to improve liver function in patients with cirrhosis with hypoxemia.     

肾上腺髓质素和内皮素-1在大鼠肝肺综合征发病机制中的作用

[目的]探讨肝肺综合征(HPS)的发病机制.[方法]采用胆总管结扎(CBDL)术制备大鼠HPS模型,观察肺组织肾上腺髓质素(ADM)、内皮素-1(ET-1)及其受体(ETRA和ETRB)的表达和分布.[结果]在大鼠HPS形成过程中,血浆和肺组织中ADM、ET-1水平动态升高,且与肺泡-动脉氧分压差(A-aDO2)正相关;HPS大鼠肺组织中ADM、内皮素前体原(ppET-1 mRNA)的表达较假手术组明显增强,差异均有统计学意义(P＜0.05).HPS大鼠肺血管ETRA的分布及染色强度与假手术组比较无明显变化,而ETRB在远端肺小动脉和小静脉内膜上表达明显增强.图像分析结果显示CBDL 5周(w)组大鼠ETRA染色面积、平均积分光密度值与假手术组比较差异无统计学意义(P＞0.05),而CBDL 5 w组大鼠ETRB染色面积和平均积分光密度值明显高于假手术组,差异均有统计学意义(P＜0.05).[结论]扩血管物质ADM和缩血管物质ET-1的共同作用可能参与HPS的发生,肺组织中升高的ET-1可能更多地通过与在肺血管表达增强的ETRB结合从而扩张肺血管.     

Prognostic significance of the hepatopulmonary syndrome in patients with cirrhosis

BACKGROUND AND AIMS: The hepatopulmonary syndrome (HPS) has been defined by chronic liver disease, arterial deoxygenation, and widespread intrapulmonary vasodilation. Mortality of patients with HPS is considered to be high, but the effect of HPS on survival in patients with cirrhosis remains unclear. METHODS: A total of 111 patients with cirrhosis were studied prospectively by using transthoracic contrast echocardiography for detection of pulmonary vasodilation, blood gas analysis, and pulmonary function test. Twenty different clinical characteristics and survival times were noted. RESULTS: Twenty-seven patients (24%) had HPS. Their mortality was significantly higher (median survival, 10.6 months) compared with patients without HPS (40.8 mo, P < 0.05), even after adjusting for liver disease severity (2.9 vs. 14.7 months in Child-Pugh class C with [n = 15] and without HPS [n = 35, P < 0.05]; 35.3 vs. 44.5 months in Child-Pugh class B with [n = 7] and without HPS [n = 23, P = NS]), and exclusion of patients who underwent liver transplantation during follow-up (median survival 4.8 vs. 35.2 months, P = 0.005). Causes of death were mainly nonpulmonary and liver-related in the 19 patients with and the 35 patients without HPS who died. In multivariate analysis, HPS was an independent predictor of survival besides age, Child-Pugh class, and blood urea nitrogen. Mortality correlates with severity of HPS. CONCLUSIONS: The presence of HPS independently worsens prognosis of patients with cirrhosis. This should influence patient management and scoring systems and accelerate the evaluation process for liver transplantation.     

Carboxyhemoglobin levels in cirrhotic patients with and without hepatopulmonary syndrome

BACKGROUND AND AIMS: Heme oxygenase (HO) catalyzes hemoglobin into bilirubin, iron, and carbon monoxide (CO), a known vasodilator. HO expression and CO production as measured by blood carboxyhemoglobin (COHb) levels increase in experimental hepatopulmonary syndrome (HPS) and contribute to vasodilatation. Whether CO contributes to HPS in humans is unknown. Our aim was to assess if arterial COHb levels are increased in cirrhotic patients with HPS relative to those without HPS. METHODS: We collected data prospectively in stable nonsmoking outpatients with cirrhosis. Demographic and clinical data and room-air arterial blood gases were collected and analyzed. HPS was diagnosed using established criteria. RESULTS: A total of 159 patients were studied. HPS was present in 27 (17%) patients. Mean age was 52 +/- 9 years, 54% were men, and hepatitis C and/or alcohol were the most common causes (53%). Fourteen percent were Child-Pugh class A, 53% were Child-Pugh class B, and 33% were Child-Pugh class C. Demographic and clinical features were similar between HPS and non-HPS patients except for the Child-Pugh score, which was lower in patients with HPS. Arterial Pa o 2 levels were lower and the alveolar-arterial oxygen gradient was higher in patients with HPS ( P < .001). COHb levels were increased in HPS relative to non-HPS ( P < .001) and correlated with Pa o 2 ( P < .001) and Aa po 2 ( P < .001) levels. CONCLUSIONS: COHb levels are increased in cirrhotic patients with HPS and correlate with gas exchange abnormalities. These results are consistent with findings in experimental HPS and suggest that CO may contribute to human HPS.     

Cirrhotic rats with bacterial translocation have higher incidence and severity of hepatopulmonary syndrome

BACKGROUND: Bacterial translocation, that is, extra-intestinal dissemination of gut bacteria, occurs in approximately 50% of humans and rats with cirrhosis and plays a significant role in enhanced tumor necrosis factor-alpha (TNF-alpha) production. The authors' previous studies have indicated that prevention of bacterial translocation with norfloxacine or inhibition of TNF-alpha with pentoxifylline treatment decreased both the incidence and severity of hepatopulmonary syndrome by attenuating the induction of pulmonary intravascular macrophages in cirrhotic rats. In the present study the hypothesis was tested that the cirrhotic rats with bacterial translocation had higher TNF-alpha production, higher level of sequestration of macrophages in pulmonary vessels, and increased incidence and severity of hepatopulmonary syndrome. METHODS: Rats were studied 5 weeks after common bile duct ligation or sham operation. Bacterial translocation was defined by positive mesenteric lymph node cultures. Hepatopulmonary syndrome was assessed by measurements of alveoloarterial oxygen difference (AaPO(2)) and intrapulmonary shunt. The TNF-alpha concentration in plasma was measured by ELISA. Pulmonary intravascular macrophage sequestration was assessed by lung morphometric analysis. RESULTS: Bacterial translocation occurred in 48% of cirrhotic rats. Plasma concentrations of TNF-alpha and the percentage of vessels with pulmonary intravascular macrophages were higher in the cirrhotic rats with bacterial translocation. Rats with bacterial translocation also had a higher incidence (9% vs 63%, P < 0.01) and severity of hepatopulmonary syndrome, as indicated by higher levels of both AaPO(2) and intrapulmonary shunt. CONCLUSIONS: These results suggest that bacterial translocation may play a role in the pathogenesis of hepatopulmonary syndrome by inducing pulmonary intravascular macrophages through TNF-alpha upregulation.     

Clinical features of hepatopulmonary syndrome in cirrhotic patients

AIM:To evaluate the frequency,clinical andparaclinical features of hepatopulmonary syndrome(HPS)and to determine their predictive values in di-agnosis of this syndrome in patients in Iran.METHODS:Fifty four cirrhotic patients underwentcontrast enhanced echocardiography to detect intra-pulmonary and intracardiac shunts by two cardiolo-gists.Arterial blood oxygen,O_2 gradient(A-a)andorthodoxy were measured by arterial blood gas(ABG)test.The patients positive for diagnostic criteria ofHPS were defined as clinical HPS cases and thosemanifesting the intrapulmonary arterial dilation but noother criteria(arterial blood hypoxemia)were definedas IHPS cases.HPS frequency,sensitivity,positive andnegative predictive values of clinical and paraclinicalfeatures were studied.RESULTS:Ten(18.5%)and seven(13%)cases hadclinical and subclinical HPS,respectively.The mostcommon etiology was hepatitis B.Dyspnea(100%)and cyanosis(90%)were the most prevalent clinicalfeatures.Dyspnea and clubbing were the most sen-sitive and specific clinical features respectively.Nosignificant relationship was found between HPS andsplenomegaly,ascites,edema,jaundice,oliguria,andcollateral veins.HPS was more prevalent in hepatitisB.PaO_2<70 and arterial-alveolar gradient had thehighest sensitivity in HPS patients.Orthodoxy speci- ficity was 100%CONCLUSION:Clubbing with positive predictive val-ue(PPV)of 75% and dyspnea with negative predic-tive value(NPV)of 75% are the best clinical factorsin diagnosis of HPS syndrome.PaO_2<70 and P(A-a)O_2>30 and their sum,are the most valuable negativeand positive predictive values in HPS patients.     

肝硬化合并呼吸睡眠暂停32例分析

目的发现晚期肝硬化会出现呼吸睡眠暂停。方法32例肝硬化患者应用携带式多频道睡眠记录仪进行夜间呼吸暂停,其中Child—Pugh分级A级8例、B级10例、C级14例。结果肝硬化出现呼吸睡眠暂停,C组10例（占71．4％）明显高于A组1例（占12．5％）和B组4例（占40％）。结论肝硬化进入晚期阶段,会出现睡眠呼吸暂停。     

Diagnosis of hepatopulmonary syndrome with contrast transthoracic echocardiography and histological confirmation

ABSTRACT— We report a patient with cirrhosis and hepatopulmonary syndrome. This syndrome is an entity characterized by anomalies in the arterial oxygenation in patients with chronic hepatic disease and/or portal hypertension and demonstration of pulmonary vasodilatation (PV) in absence of primary cardiac or pulmonary disease. We show that the finding of PV with transthoracic contrast enhanced echocardiography (TCEE) in the diagnosis of PV is real and corresponds to direct measurement of capillary diameter by morphometry.     

Hepatopulmonary syndrome in noncirrhotic portal hypertensive patients

Hepatopulmonary syndrome has yet not been sufficiently assessed in noncirrhotic portal hypertension. The prevalence of hepatopulmonary syndrome was determined in 31 consecutive patients with noncirrhotic portal hypertension (19 idiopathic portal hypertension, 7 portal vein thrombosis, 5 congenital hepatic fibrosis) and 46 patients with liver cirrhosis. Contrast echocardiography was carried out in all patients. Macroaggregated albumin lung perfusion scans were performed in patients with positive contrast echocardiogram. Hepatopulmonary syndrome was detected in 5 (10.8%) cirrhotic and 3 (9.7%) noncirrhotic portal hypertensive patients (2 idiopathic portal hypertension, 1 portal vein thrombosis). All patients with hepatopulmonary syndrome had an increased shunt fraction (13–62%) and a decreased diffusion capacity of carbon monoxide (40–79%), and 7 of them were hypoxemic (P_aO₂, 31.6–69.8 mm Hg). These findings show that hepatopulmonary syndrome may occur in both liver cirrhosis and noncirrhotic portal hypertension and that portal hypertension is the predominant etiopathogenic factor related to hepatopulmonary syndrome.     

Left ventricle enlargement and increased systolic velocity in the mitral valve are indirect markers of the hepatopulmonary syndrome

Background and aims: Hepatopulmonary syndrome (HPS) has been associated with left atrial enlargement, but the presence of other markers of left and right diastolic and/or systolic cardiac dysfunction has not been clarified. We prospectively evaluated the possible associations between echocardiographical‐Doppler findings and HPS. Methods: Seventy‐nine cirrhotic patients without endogenous heart or pulmonary disease were included. HPS was diagnosed by the presence of increased arterial–alveolar‐difference and intrapulmonary right‐to‐left shunt at contrast‐enhanced transthoracic echocardiography. Echocardiographical systolic and diastolic indices, tissue Doppler imaging (TDI) of mitral and tricuspid annular motion and M‐mode echocardiography measurements were recorded. Results: Hepatopulmonary syndrome was diagnosed in 12 (15.2%) patients. Patients with compared with those without HPS had significantly younger age, albumin levels and saturation of oxygen (SaO₂) in an erect position, but higher left ventricular end diastolic diameter (LVEDD), ejection fraction, E‐wave peak velocity of tricuspid valve, left atrial volume, TDI E wave (early diastolic period) at the right free wall/tricuspid annulus (cm/s) and TDI S wave (systolic) at the left lateral wall/mitral annulus (TDI Smv). In multivariate analysis, the presence of HPS was found to be independently associated with younger age (P=0.027), lower SaO₂ in an erect position (P=0.023), higher LVEDD (P=0.019) and higher TDI Smv (P=0.026). LVEDD and TDI Smv offered good diagnostic accuracy for HPS diagnosis (AUROC/c‐statistic: 0.724 and 0.736 respectively). Conclusions: We confirmed that in patients with cirrhosis, the development of HPS is associated with higher cardiac output and hyperdynamic circulation. Left ventricle enlargement and higher systolic velocity in the mitral valve represent satisfactory indirect markers of HPS.     

Echocardiographic detection of intrapulmonary shunting in a patient with hepatopulmonary syndrome: case report and review of the literature

Transthoracic echocardiography is a useful tool in the evaluation of patients with intrapulmonary and intracardiac shunts. We describe a case of a 49-year-old female with severe hypoxemia in the setting of aortic stenosis and cirrhosis of the liver. The use of agitated saline contrast during an echocardiography study helped to establish the diagnosis of intrapulmonary arteriovenous shunting consistent with the hepatopulmonary syndrome, thereby confirming the etiology of her symptoms and laboratory findings. This case report highlights the utility of echocardiography in diagnosing intrapulmonary shunts and assists in the understanding of the pathophysiology of hypoxemia in such patients.