Role of 2-dimensional Doppler echo-cardiography in screening portopulmonary hypertension in portal hypertension patients

BACKGROUND: Portopulmonary hypertension (PPH) is difficult to recognize in the early and middle stages because it is frequently asymptomatic. As right ventricular function is impaired in patients with moderate and severe PPH, any dramatic hemodynamic changes in liver transplantation or other procedures may result in death from pulmonary and cardiac events. In this study, we investigated the prevalence of PPH in patients with portal hypertension (PHT) mainly caused by hepatitis B virus, and evaluated the effect of 2-dimensional Doppler echocardiography (2D-ECHO) in screening for PPH. METHODS: One hundred and five PHT patients received transthoracic 2D-ECHO preoperatively, systolic pulmonary arterial pressure (SPAP, normal range <30 mmHg) and pulmonary acceleration time (PAT, normal range >= 120 msec) were measured to screen for PPH (positive result: SPAP >= 30 mmHg and/or PAT <100 msec). Subsequently, pulmonary hemodynamic parameters were measured by right heart catheterization (RHC) for definitive diagnosis of PPH. The results of the two methods were compared to assess the screening effect of 2D-ECHO. RESULTS: The prevalence of PPH in this study was 3.8% (4/105). About 90% (95/105) of patients had a detectable tricuspid regurgitation by 2D-ECHO and the mean SPAP was 27.7 +/- 5.9 mmHg. Twenty-two of these 95 patients had an SPAP >30 mmHg. The mean PAT of all patients was 140 23 msec and 5 were <100 msec. Twenty-two patients were screened out by 2D-ECHO and 4 were diagnosed by RHC. A positive significant correlation (r=0.55, P<0.01) was found between SPAP measured by 2D-ECHO and mean pulmonary artery pressure (MPAP) measured by RHC, and a weak but significant negative correlation (r=-0.27, P=0.005) existed between PAT and pulmonary vascular resistance (PVR). The sensitivity, specificity, agreement rate, positive predictive value and negative predictive value of the screening test were 100%, 82%, 83%, 18% and 100%, respectively. CONCLUSIONS: The prevalence of PPH in this study is lower than in Western countries. As a screening test, 2D-ECHO has very high sensitivity and negative predictive value. A negative test result can directly be used to exclude PPH, while a positive result should be confirmed by RHC.

Portopulmonary hypertension and hepatopulmonary syndrome

Portopulmonary hypertension (POPH) and hepatopulmonary syndrome (HPS) are two frequent complications of liver disease, with prevalence among liver transplant candidates of 6% and 10%, respectively. Both conditions result from a lack of hepatic clearance of vasoactive substances produced in the splanchnic territory. Subsequently, these substances cause mainly pulmonary vascular remodeling and some degree of vasoconstriction in POPH with resulting elevated pulmonary pressure and right ventricular dysfunction. In HPS the vasoactive mediators cause intrapulmonary shunts with hypoxemia. Medical treatment is disappointing overall. Whereas liver transplantation (LT) results in the disappearance of HPS within six to twelve months, its effect on POPH is highly unpredictable. Modern strategies in managing HPS and POPH rely on a thorough screening and grading of the disease&#x02019;s severity, in order to tailor the appropriate therapy and select only the patients who will benefit from LT. The anesthesiologist plays a central role in managing these high-risk patients. Indeed, the important hemodynamic and respiratory modifications of the perioperative period must be avoided through continuation of the preoperatively initiated drugs, appropriate intraoperative monitoring and proper hemodynamic and respiratory therapies.

Portopulmonary hypertension and serum endothelin levels in hospitalized patients with cirrhosis

BACKGROUND:Cirrhosis is associated with several extrahepatic manifestations including portopulmonary hypertension (PPHT).Recent data suggest that endothelins (ETs) are related to the pathophysiology of PPHT.The study aimed to measure serum ET levels in hospitalized cirrhotic patients and to determine their association with PPHT and patient outcome.METHODS:Fifty-seven cirrhotic patients [43 males;median age 58 (28-87) years] underwent Doppler echocardiography.Patients with systolic pulmonary arterial pressure ≥40 mmHg and pulmonary acceleration time <100 ms were deemed to have PPHT.ET-1,2,and 3 serum levels were measured with an ELISA assay.All-cause mortality was recorded over a median period of 24 months.RESULTS:Nine out of 57 patients (15.8%) had PPHT.Among various clinical variables,only autoimmune hepatitis was associated with PPHT (OR=11.5;95% CI,1.58-83.4;P=0.01).ET-1 levels [9.1 (1.6-20.7) vs 2.5 (1.4-9.2) pg/mL,P=0.02] and the ET-1/ET-3 ratio [4.73 (0.9-22.4) vs 1.6 (0.3-10.7),P=0.02] were significantly higher in patients with PPHT than in those without.ET-2 and ET-3 levels did not differ between the two groups.There was no difference in survival between the two groups,although ET-1 levels were associated with an adverse outcome in Cox regression analysis (HR=1.11;95% CI,1.02-1.22;P=0.02 per unit increase in ET-1).CONCLUSION:Our data suggest that ET-1 and the ET-1/ET-3 ratio are elevated in patients with PPHT and that ET-1 is associated with a poor outcome irrespective of PPHT.

Clinical management of portopulmonary hypertension

BACKGROUND: Portopulmonary hypertension (PPH) is defined as the development of pulmonary arterial hypertension associated with increased pulmonary vascular resistance complicated by portal hypertension, with or without advanced hepatic disease. In spite of the relatively rare prevalence, the clinical implications of PPH are significant. It has high perioperative morbidity and mortality. This review is an update of current pathogenesis, diagnosis and therapy of PPH. DATA SOURCES: An English-language literature search was conducted using PubMed (1980-2006) on portopulmonary hypertension. RESULTS: Echocardiographically identified patients with elevated pulmonary artery systolic pressure (>50 mmHg) receive right heart catheterization. Epoprostenol (prostacyclin), a potent pulmonary and systemic vasodilator with anti-platelet aggregating activity, and bosentan, an endothelin receptor antagonist, have so far proven beneficial to patients with PPH. CONCLUSIONS: After an accurate diagnosis of PPH treatment should (at a minimum) focus on reduction of mean pulmonary arterial pressure to less than 35 mmHg prior to orthotopic liver transplantation. However, orthotopic liver transplantation currently remains the only therapy to resolve PPH.

Pathophysiology and therapeutic advances in portopulmonary hypertension

Portopulmonary hypertension(PoPH)is a syndrome characterized by unexplained pre-capillary pulmonary hypertension in the presence of portal hypertension.It is classified under pulmonary arterial hypertension(PAH)in which multiple complex mechanisms including BMP9/BMPR2/ALK1 pathways,hyperdynamic circulation,estrogen pathways,NK cells,and oxidative stress were involved.Despite guideline-based treatments such as phosphodiesterase 5(PDE 5)inhibitors and endothelin receptor antagonists are effective for PoPH,but focusing on the BMP9/BMPR2/SMAD and estrogen pathways may be the new strategy to develop more comprehensive treatments.

Portopulmonary hypertension: Current developments and future perspectives

Portopulmonary hypertension(POPH)is a severe pulmonary vascular disease secondary to portal hy-pertension and a subset of Group 1 pulmonary hypertension(PH).The pathological changes of POPH are indistinguishable from other PH phenotypes,including endothelial dysfunction,pulmonary vasocon-striction,and vascular remodeling.These changes cause a progressive increase in pulmonary vascular resistance and afterload of the right ventricle,eventually leading to severe right heart failure.The prognosis of POPH is extremely poor among untreated patients.POPH is associated with a high risk of death after liver transplantation(LT),and severe POPH is considered an absolute contraindication for LT.However,pulmonary arterial hypertension(PAH)-targeted therapies are administered to patients with POPH,and aggressive drug treatment significantly optimizes pulmonary hemodynamics and reduces the risk of death.Therefore,early diagnosis,aggressive PAH-targeted therapies,and proper selection of liver transplant candidates are vital to reduce the risk of surgery and improve clinical outcomes.This article aims to review the results of previous studies and describe biological mechanisms,epidemiology,po-tential risk factors,and diagnostic approaches of POPH.Moreover,we introduce recent therapeutic in-terventions for the early diagnosis of POPH and efficient clinical management decisions.

Extrahepatic complications to cirrhosis and portal hypertension: Haemodynamic and homeostatic aspects

In addition to complications relating to the liver, patients with cirrhosis and portal hypertension develop extrahepatic functional disturbances of multiple organ systems. This can be considered a multiple organ failure that involves the heart, lungs, kidneys, the immune systems, and other organ systems. Progressive fibrosis of the liver and subsequent metabolic impairment leads to a systemic and splanchnic arteriolar vasodilatation. This affects both the haemodynamic and functional homeostasis of many organs and largely determines the course of the disease. With the progression of the disease, the circulation becomes hyperdynamic with cardiac, pulmonary as well as renal consequences for dysfunction and reduced survival. Infections and a changed cardiac function known as cirrhotic cardiomyopathy may be involved in further aggravation of other complications such as renal failure precipitatingthe hepatorenal syndrome.Patients with end-stage liver disease and related complications as for example the hepatopulmonary syndrome can only radically be treated by liver transplantation.As a bridge to this treatment,knowledge on the mechanisms of the pathophysiology of complications is essential for the choice of vasoactive drugs,antibiotics,drugs with specific effects on fibrogenesis and inflammation,and drugs that target specific receptors.

Cardiopulmonary,complications in chronic liver disease

Patients with cirrhosis and portal hypertension exhibit characteristic cardiovascular and pulmonary hemodynamic changes. A vasodilatatory state and a hyperdynamic circulation affecting the cardiac and pulmonary functions dominate the circulation. The recently defined cirrhotic cardiomyopathy may affect systolic and diastolic functions, and imply electromechanical abnormalities. In addition, the baroreceptor function and regulation of the circulatory homoeostasis is impaired. Pulmonary dysfunction involves diffusing abnormalities with the development of the hepatopulmonary syndrome and portopulmonary hypertension in some patients. Recent research has focused on the assertion that the hemodynamic and neurohumoral dysregulation are of major importance for the development of the cardiovascular and pulmonary complications in cirrhosis. This aspect is important to take into account in the management of these patients.

Cirrhosis and its complications:Evidence based treatment

Cirrhosis results from progressive fibrosis and is the final outcome of all chronic liver disease. It is among the ten leading causes of death in United States. Cirrhosis can result in portal hypertension and/or hepatic dysfunction. Both of these either alone or in combination can lead to many complications, including ascites, varices, hepatic encephalopathy, hepatocellular carcinoma, hepatopulmonary syndrome, and coagulation disorders. Cirrhosis and its complications not only impair quality of life but also decrease survival. Managing patients with cirrhosis can be a challenge and requires an organized and systematic approach. Increasing physicians&#x02019; knowledge about prevention and treatment of these potential complications is important to improve patient outcomes. A literature search of the published data was performed to provide a comprehensive review regarding the management of cirrhosis and its complications.

Pulmonary complications of hepatic diseases

Severe chronic liver disease(CLD) may result from portal hypertension, hepatocellular failure or the combination of both. Some of these patients may develop pulmonary complications independent from any pulmonary pathology that they may have. Among them the hepatopulmonary syndrome(HPS), portopulmonary hypertension(PPH) and hepatic hydrothorax(HH) are described in detail in this literature review. HPS is encountered in approximately 15% to 30% of the patients and its presence is associated with increase in mortality and also requires liver transplantation in many cases. PPH has been reported among 4%-8% of the patient with CLD who have undergone liver transplantation. The HH is another entity, which has the prevalence rate of 5% to 6% and is associated in the absence of cardiopulmonary disease. These clinical syndromes occur in similar pathophysiologic environments. Most treatment modalities work as temporizing measures. The ultimate treatment of choice is liver transplant. This clinical review provides basic concepts; pathophysiology and clinical presentation that will allow the clinician to better understand these potentially life-threatening complications. This article will review up-to-date information on the pathophysiology, clinical features and the treatment of the pulmonary complications among liver disease patients.

Cardiac Syndromes in Liver Disease:A Clinical Conundrum

Understanding the interaction between the heart and liver is pivotal for managing patients in whom both organs are affected.Studies have shown that cardio-hepatic interactions are bidirectional and that their identification,assessment,and treatment remain challenging.Congestive hepatopathy is a condition that develops in the setting of long-standing systemic venous congestion.If left untreated,congestive hepatopathy may lead to hepatic fibrosis.Acute cardiogenic liver injury develops as a combination of venous stasis and sudden arterial hypoperfusion due to cardiac,circulatory,or pulmonary failure.The treatment of both conditions should be directed toward optimizing the cardiac substrate.Hyperdynamic syndrome may develop in patients with advanced liver disease and lead to multiorgan failure.Cirrhotic cardiomyopathy or abnormalities in pulmonary vasculature,such as hepatopulmonary syndrome and portopulmonary hypertension may also develop.Each complication has unique treatment challenges and implications for liver transplantation.The presence of atrial fibrillation and atherosclerosis in liver disease brings another layer of complexity,particularly in terms of anticoagulation and statin use.This article provides an overview of cardiac syndromes in liver disease,focusing on current treatment options and future perspectives.