Hepatopulmonary syndrome (HPS) is a disease condition characterized by altered pulmonary physiology in the form of hypoxemia and pulmonary vasodilatation occurring secondary to a preexisting progressive liver disease. The obvious clinical findings of HPS include dyspnea or platypnea, cyanosis, spider nevi, digital clubbing, increased nitrous oxide (NO) levels and reduced partial pressure of oxygen in the lungs. Definite treatment for HPS is liver transplantation.
HPS does not present with specific clinical findings on a physical examination. The symptoms of HPS are atypical and appear with several other hepatic and non-hepatic illnesses too. However, HPS can be suspected in the presence of severe hypoxemia (characterized by partial pressure of oxygen reduced to less than 66 mm of mercury), cyanosis, spider nevi and digital clubbing . Dyspnea at rest is a non-specific but obvious finding of HPS. However, this symptom is also ensued by other hepatic diseases that include anemia, ascites and muscle atrophy.
Diagnosis of HPS is based on the presence of an obvious liver disease, moderate to severe dyspnea, severe hypoxemia and cyanosis. A number of diagnostic tests are available to confirm diagnosis in the presence of these findings.
Contrast echocardiography is another important diagnostic tool  that detects abnormally increased venous blood flow. Other tests that may be helpful in confirmation of HPS include pulmonary angiography and technetium labeled albumin. However, angiography is not necessary in the absence of thromboembolism in HPS.
Treatment is based on lifestyle modification, pharmacologic therapy and in advanced cases, surgery. Once diagnosed with HPS, the patient is recommended to follow up regularly for approximately three years.
Patients with HPS are advised to restrict alcohol consumption and limit the use of hepatotoxic drugs in order to restrict further deterioration in the liver. In patients with cirrhosis, a sodium-containing diet is contraindicated to reduce fluid retention and prevent worsening of ascites. Because of the presence of hypoxemia in HPS, it is recommended to avoid cardioactive exercises that increase the oxygen demand.
No definite class of drugs is indicated for treating HPS although empiric therapy can be initiated to minimize symptoms. Excessive pulmonary vasodilation and reduced arterial oxygenation is managed by pharmacologic intervention. Patients with HPS presenting with manifestations or risk of gastroesophageal bleeding can be treated with non-selective beta adrenergic blockers . Prophylactic use of antimicrobials is recommended to reduce the level of severeness in HPS .
The only treatment that offers complete resolution is liver transplantation. It results in eradication of hypoxemia and improved oxygenation in more than 85% of the cases .
The prevalence of HPS is determined on diagnostic basis and methods. The estimations vary widely from patient to patient, ranging from as low as 4% to up to 47% . HPS may affect patients of all age groups.
The significant elevation in concentration of the endogenous nitrous oxide (NO) leads to the development of pulmonary vasodilatation in HPS. However, the levels are normalized following liver transplantation . The precise mechanism behind vascular dilatation is not fully understood yet but it is thought to result from vascular remodeling, angiogenesis, portopulmonary anastomoses and pulmonary arteriovenous shunts.
Pulmonary vasodilatation results in an increased flow of venous blood into the pulmonary veins. As a result, the normal pulmonary ventilation becomes insufficient to oxygenate the abnormally increased blood flow. This results in hypoxemia of the pulmonary blood vessels. Moreover, the diffusing capacity of carbon monoxide is impaired due to the dilation of the alveolar–capillary interface. In consequence, the equilibration of carbon monoxide with hemoglobin is proceeds only incompletely.
Several experimental studies have also indicated the association of the inflammatory mediators endothelin-1 and tumor necrosis factor-α in the pathogenesis of HPS .
Prevention of HPS remains unknown due to a lack of scientific data on the exact etiology of the disease.
Hepatopulmonary syndrome (HPS) is a rare disease associated with decreased arterial oxygenation (hypoxemia) in the lungs occurring as a result of pulmonary vasodilation in the presence of an already existing, advanced liver disease . The most obvious clinical findings of HPS comprise liver disease, pulmonary vasodilatation and pulmonary hypoxemia. However, the presence of a hepatic dysfunction does not necessarily permit a conclusion to the severeness of HPS. Timely diagnosis and identification of the level of severeness in HPS is paramount in determining the prognosis and for planning the liver transplantation.
The pulmonary vessels in HPS are dilated and display a substantially increased blood flow. Another important finding of HPS is pulmonary arterial hypoxemia, the definite etiology of which remains unknown. Hypoxemia in HPS is detected by measurement of the partial pressure of oxygen which is greatly reduced. Another more sensitive and reliable method to determine the degree of the pulmonary oxygenation is alveolar arterial oxygen gradient. It also measures alterations in the levels of arterial carbon dioxide along with oxygen and detects respiratory alkalosis .
HPS can be classified into two different forms. Type I is the common form, in which vasodilatation occurs at the time of gaseous exchange. This then results in reduced oxygenation at the level of alveoli and altered ventilation. Type II HPS accounts for 10% of the total cases of HPS. This type is characterized by the presence of anatomic shunts which results in compromised gaseous exchange.
Timely diagnosis of HPS is important to prevent complications and to minimize further liver damage. Common diagnostic tests for HPS include pulse oximetry, X-ray, measurement of ABGs and pulmonary echocardiography.
The most definite and permanent treatment of HPS is liver transplantation. Pharmacological treatment is aimed at providing empirical therapy by reducing symptoms. Severe dyspnea occurring due to hypoxemia is treated with administration of supplemental oxygen.
Hepatopulmonary syndrome (HPS) is a disease affecting liver and lungs. The liver is primarily affected, which leads to an involvement of the lungs as well. The specific cause behind the combined involvement of both organs is not known yet. HPS can occur in all age groups. Early diagnosis and management of HPS can help in minimizing further deterioration and disease complications.
The classical clinical findings of HPS include liver disease, abnormally increased blood flow inside the pulmonary blood vessels (intrapulmonary vascular dilatation) and decreased oxygen levels in the blood (hypoxemia).
The exact cause of HPS remains unidentified. However, certain mechanisms that are believed to be involved in the development of HPS include
The symptoms of HPS are both liver related and lung related. The most obvious clinical finding is hypoxemia along with bluish discoloration of the skin (cyanosis). Enlargement of finger tips (digital clubbing) and appearance of spider-like blood vessels on the skin (spider nevi) are typically observed in individuals with HPS. Other signs include difficulty in breathing when at a resting state (dyspnea), difficulty breathing in a standing position (platypnea), orthodexia, increased heart rate (tachycardia) and development of esophageal varices.
Diagnosis of HPS requires an evaluation of the signs and symptoms, a physical examination and a series of tests. Diagnostic tests include chest X-ray, screening of HPS with pulmonary echocardiography and measurement of arterial blood gases (ABGs). The abnormally increased blood flow in HPS can be detected by pulmonary echocardiography. The partial pressure of oxygen less than 70 mm of Hg indicates the presence of hypoxemia.
Treatment of HPS is largely based on symptomatic management and prevention of further worsening of the disease. The only definite treatment that guarantees complete cure is liver transplantation. Supportive treatment is provided with oxygen supplementation to improve ventilation. Abnormal intrapulmonary vasodilation can be managed by administration of nitrous oxide inhibitor. In the presence of chronic liver disease and cirrhosis, propanalol and nadolol are indicated in patients to prevent esophageal varices and portal hypertension.