Topic Editor: Robert Giles, MBBS, BPharm
Review Date: 9/11/2012
Definition
Hepatopulmonary syndrome (HPS) is defined as the following triad:
- Patient who has hepatic cirrhosis or portal hypertension
- Presence of alveolar-arterial (A-a) gradient >15 mmHg (at sea level)
- Presence of pulmonary vascular dilation
Description
- HPS occurs most frequently in hepatic cirrhosis, but can occur in patients with extrahepatic portal venous obstruction
- Patients are usually asymptomatic, with an insidious onset of dyspnea
- The etiology of HPS is unknown; however, some hypothesize that there is a defect in the synthesis and metabolism of pulmonary vasoactive substances by an impaired liver. This is presumed to lead to the formation of functional intrapulmonary vascular dilation with hypoxemia
- HPS generally requires liver transplantation
- Rarely, pharmacologic and/or interventional radiology options may be offered
Epidemiology
Incidence/prevalence
- Estimates of the prevalence of HPS in adults with cirrhosis vary depending on the diagnostic criteria used but ranges from 4% to 29%
- HPS occurs in just 2-3% of children with cirrhosis or severe portal hypertension
Age
- Data on age prevalence is lacking. It should be noted this condition occurs when liver disease is present, and in that setting occurs much more rarely in children than adults
Gender
- Data on gender prevalence is lacking. It is unclear whether there is a predilection in the setting of established liver disease to develop HPS
Risk factors
- HPS can occur in patients with any degree or etiology of liver disease
- HPS usually occurs in patients with established cirrhosis and/or portal hypertension
- There is no clear relationship between the severity of hepatic dysfunction and the degree of hypoxemia
Etiology
- The etiology has not be definitively determined
- Some hypothesize that there is a defect in the synthesis and metabolism of pulmonary vasoactive substances by an impaired liver. This is presumed to lead to formation of functional intrapulmonary vascular dilation with hypoxemia
- Pulmonary vascular dilation tends to occur at the lung bases. This results in the patient being most hypoxemic when standing, with improvement on lying. This finding is explained by increased blood flow to pulmonary dilation with standing, with exacerbation of the shunt worsening hypoxemia
- Increased cardiac output (CO) and hyperdynamic circulation associated with liver disease reduces transit time of blood in the lung vasculature. This results in the time blood is exposed to oxygen diffusion being reduced
History
- Patients with HPS typically present with an insidious onset of dyspnea on a background of known liver disease. The time between first presentation of dyspnea and diagnosis of HPS is variable
- Dyspnea may be exacerbated by sitting up and improved with lying down (platypnea)
Physical findings on examination
- Signs of chronic liver disease may be evident:
- Anorexia
- Ascites
- Caput medusa
- Clubbing
- Contracted liver
- Dupuytrens contractures
- Gynecomastia
- Hepato and/or splenomegaly
- Jaundice
- Muscle wasting
- Palmar erythema
- Telangiectasias/Spider nevi-angiomas
- Signs pertaining to hyperdynamic circulation characterized by systemic vasodilatation and increased cardiac output are common in patients with advanced liver disease. These signs are often present in patients with HPS
- In the presence of chronic liver disease orthodeoxia, which is arterial deoxygenation worsened by upright position, often accompanies platypnea. This finding is highly specific for HPS
- Orthodeoxia is present when the PaO2 decreases by >4 mmHg or arterial saturation decreases by >5% when the patient moves from a supine to an upright position
- Room air pulse oximetry 96% in patients with liver disease has been used as a sensitive screening test for HPS
Blood Tests findings
- Arterial blood gas analysis : May be used to identify hypoxemia and should be performed in the upright position and on room air when possible
- PaO2 80 mmHg on room air suggests HPS
- A room air A-a oxygen gradient Aa Gradient
>15mmHg is the most sensitive measure
Other laboratory test findings
- Pulmonary function test: Should be performed to rule out common intrinsic pulmonary disorders such as chronic obstructive pulmonary disease (COPD)
- Patients with HPS will show nonspecific reduction in lung diffusion capacity testing (DLCO)
Radiographic findings
- Chest x-ray: May show nonspecific, mild interstitial pattern in the lower lung that may reflect existence of diffuse pulmonary vascular dilatation
- CT pulmonary angiogram: Useful to rule out pulmonary embolism
- Contrast-enhanced echocardiography is the preferred screening test for HPS. In this test, agitated saline is injected intravenously. The resulting micro-bubbles produce artifacts which are visible on routine echocardiography
- Presence of micro-bubbles in the left atrium demonstrates the existence of a right to left shunt secondary to intrapulmonary vascular dilation or cardiac shunt
- The timing of micro-bubble appearance helps differentiate between the two possible etiologies
- Scintigraphic perfusion scanning: Technetium-99m-labeled albumin is normally filtered by lung tissue after injection. If significant uptake is found in other organs (eg brain or spleen) then indicates intrapulmonary vascular dilation or right-to-left cardiac shunt
Other diagnostic test findings
- Pulmonary angiography: May be considered in cases involving large arteriovenous malformations which might benefit from embolization
Prognosis
- Mortality of patients with HPS is high
- A prospective study showed that HPS worsens the prognosis in hepatic cirrhosis
Associated Conditions
Pregnancy/Pediatric effects on condition
- Pregnancy may induce HPS in an otherwise asymptomatic cirrhotic patient
- HPS occurs in only 2-3% of children with cirrhosis or severe portal hypertension
Abbreviations
ICD-9-CM
- 573.5 Hepatopulmonary syndrome
ICD-10-CM
- K76.81 Hepatopulmonary syndrome
