Hepatopulmonary syndrome results from the formation of microscopic intrapulmonary arteriovenous dilations in patients with chronic liver disease typically when complicated by portal hypertension. The mechanism is unknown but is thought to be due to increased hepatic production or decreased hepatic clearance of vasodilators. The vascular dilations cause overperfusion relative to ventilation, leading to hypoxemia, particularly because patients have an increased cardiac output resulting from systemic vasodilation.
Hepatopulmonary syndrome is associated with reduced levels of bone morphogenetic protein 9 (BMP9) and BMP10 level when compared to control patients with advanced liver disease without hepatopulmonary syndrome. Lower BMP9 levels were further associated with more severe hepatopulmonary syndrome (1).
Because the lesions frequently are more numerous at the lung bases, hepatopulmonary syndrome can cause platypnea (dyspnea) and orthodeoxia (hypoxemia), which occur when the patient is seated or standing and are relieved by recumbency. Most patients also have characteristic findings of chronic liver disease, such as spider angiomas. About 20% of patients present with pulmonary symptoms alone.
Hepatopulmonary syndrome should be suspected in patients with known liver disease who report dyspnea (particularly platypnea). Patients with such symptoms should have pulse oximetry. If the symptoms are severe (eg, dyspnea at rest), arterial blood gasses should be measured with the patient breathing room air and 100% oxygen to determine shunt fraction.
A useful diagnostic test is contrast echocardiography. Intravenous microbubbles from agitated saline that are normally trapped in the pulmonary capillaries rapidly (ie, within 7 heartbeats) traverse the lung and appear in the left atrium. Similarly, IV technetium-99m–labeled albumin may traverse the lungs and appear in the kidneys and brain. Pulmonary angiography may reveal a diffusely fine or blotchy vascular configuration. Angiography is generally not needed unless thromboembolism is suspected.
The main treatment is supplemental oxygen for symptoms. Other therapies, such as somatostatin to inhibit vasodilation, are of modest benefit in only some patients. Coil embolization is virtually impossible because of the number and size of the lesions. Inhaled nitric oxide synthesis inhibitors may be a future treatment option. Hepatopulmonary syndrome may regress after liver transplantation or if the underlying liver disease subsides. Prognosis is poor without treatment (survival < 2 years).