What is Hepatopulmonary Syndrome?
Hepatopulmonary syndrome, or HPS, was first identified in 1977. It’s a condition related to serious liver disease or high blood pressure in the vein leading to the liver (known as portal hypertension). It was noticed in patients with liver cirrhosis who had larger than usual blood vessels in their lungs. These enlarged blood vessels are thought to contribute to some of the lung problems seen in people with long-term liver disease. You see, HPS reduces the levels of oxygen in the blood due to these enlarged blood vessels in the lungs.
So, how do doctors determine if someone has HPS? They use certain criteria which include:
- The amount of pressure from the oxygen in your blood (PaO2) shouldn’t be more than 80 mm Hg when you’re breathing normal room air. Alternatively, the difference in the amount of oxygen between your airways and arteries (A-aO2) should be at least 15 mm Hg when you’re breathing normal room air. This criteria slightly changes for patients aged over 64, in which case an A-aO2 of more than 20 mm Hg is acceptable (only if they’re seated and resting).
- There should be evidence of enlarged blood vessels in the lungs. This is usually shown through specific tests, like a contrast-enhanced echocardiography or a test involving radioactivity that shows how well the lungs are working (with more than 6% indicating a problem).
- The patient has high blood pressure in the vein to the liver, whether there is liver cirrhosis or not.
The seriousness of a person’s HPS depends on their oxygen levels. For example, a mild case could have oxygen levels ≥80 mm Hg with a A-aO2 of at least 15 mm Hg while breathing room air. This would continue to escalate until it’s classed as very severe, with oxygen levels below 50 mm Hg with an A-aO2 of at least 15 mm Hg while breathing room air, or with oxygen levels less than 300 mm Hg when breathing 100% oxygen.
What Causes Hepatopulmonary Syndrome?
Hepatopulmonary syndrome (HPS) is usually linked to high blood pressure in the vein carrying blood to the liver, a condition known as portal hypertension. This commonly results from chronic liver disease or cirrhosis, which is long-term scarring of the liver. Nonetheless, portal hypertension can also cause HPS even without an underlying liver disease. It’s rare, but sudden liver diseases such as acute hepatitis causing acute liver failure can also lead to HPS. However, it’s important to note that the presence and intensity of HPS aren’t directly related to how severe the liver disease is.
Risk Factors and Frequency for Hepatopulmonary Syndrome
Hepatopulmonary syndrome (HPS) is often seen more in white people than in Hispanics or Blacks. Interestingly, it’s less frequent in individuals who smoke. Studies show that the occurrence of HPS in patients with liver cirrhosis varies from 5% to 32%. HPS tends to occur mostly in individuals with severe liver dysfunction and cirrhotic portal hypertension. However, it’s rare to find this condition in children.
- HPS is more prevalent in white people than Hispanics or Blacks.
- Smokers have a lower occurrence of HPS.
- In patients with liver cirrhosis, 5% to 32% might develop HPS.
- People suffering from severe liver dysfunction and cirrhotic portal hypertension are mostly affected by HPS.
- HPS is rarely seen in children.
Signs and Symptoms of Hepatopulmonary Syndrome
Patients with liver disease often experience breathing difficulties known as dyspnea. The onset is gradual and the breathing difficulty worsens with physical effort. In the early stages, most patients might not show symptoms. It’s also possible for patients to show signs of chronic liver disease.
Hepatopulmonary syndrome (HPS) can happen alongside other heart and lung diseases, which can worsen abnormal blood flow in the lungs. When physically examining a patient, doctors may observe:
- Bluish discoloration of the skin and mucous membranes (Cyanosis)
- Enlarged fingertips (Digital clubbing)
- Widespread small blood vessel dilations (Diffuse telangiectasia)
- Increased shortness of breath when moving from lying down to standing up (Platypnoea)
- Substantial decrease in oxygen levels in the blood when moving from lying down to standing up (Orthodeoxia)
It’s worth noting that the occurrence of orthodeoxia is highly specific for diagnosing HPS in patients with liver disease. However, this symptom’s sensitivity is low but increases with the severity of HPS.
Testing for Hepatopulmonary Syndrome
To assess if a patient has Hepatopulmonary Syndrome or HPS, doctors use several evaluation methods.
A pulse oximeter, a device used to measure the oxygen levels in your blood, is the first tool a doctor might use. If your blood oxygen saturation is below 96%, it might signify that your blood oxygen level is less than normal and the doctor will recommend you for further testing.
One of the main techniques for identifying HPS is contrast-enhanced echocardiography with agitated saline, a process that involves shaking normal salt water to create tiny bubbles. These bubbles are then inserted into a vein in your arm while a special type of ultrasound (transthoracic echocardiography) is performed on your chest. Normally, these bubbles get caught and absorbed in the lungs, but in cases of HPS, these bubbles can bypass the lungs and reach the left side of your heart, which signifies abnormal blood flow.
Alternatively, doctors could use the transesophageal echocardiogram study, which provides a detailed look at the heart and its blood flow. However, this method is more invasive and could be riskier for patients with certain conditions like cirrhosis and portal hypertension.
Radioactive lung perfusion scanning is another method to assess the blood vessels in your lungs, but it’s not as sensitive as the contrast-enhanced echocardiography. This scan involves injecting radiolabeled particles into a vein and observing their distribution in the lungs and other organs, which may help doctors understand more about blood flow in patients with HPS.
Pulmonary angiography is another tool that doctors might use. It can differentiate between two types of HPS but is more invasive and costly and less sensitive than other options.
Other tests such as chest x-rays, computerized tomography (CT), and pulmonary function tests can also be of use for the diagnosis and assessment of HPS. CT scans allow doctors to examine dilated vessels, while pulmonary function tests indicate how well your lungs are working. Chest X-rays, meanwhile, can help rule out other lung-related issues.
Treatment Options for Hepatopulmonary Syndrome
Oxygen therapy is commonly used for patients who have severe trouble getting enough oxygen (a condition known as hypoxemia). This treatment can provide relief until a more lasting solution, such as a liver transplant, is available. By enhancing oxygen levels and reducing hypoxemia, patients typically experience improved physical capability and overall quality of life.
For individuals with Hepatopulmonary Syndrome (HPS), liver transplantation is the only recognized treatment that offers long-term survival advantages. Generally, this procedure helps improve hypoxemia within 6 to 12 months. Research indicates that the concentration of oxygen in your arteries (PaO2) and the difference in oxygen partial pressures in the alveoli and arterial blood (A-aO2) typically improve quickly after transplant, mostly within 6 months. Though intrapulmonary shunts, which are abnormal direct connections from arteries to veins within the lung, reverse, the process could take longer than 6 months. DLCO, a measure of how well lungs transfer a small molecule like oxygen or carbon monoxide to your blood, has been seen to improve in a few patients in one study.
Patients with chronic liver disease who have a Model for End-Stage Liver Disease (MELD) score of 15 or more are referred for a liver transplant assessment. The MELD score is a reliable system used to gauge the severity of chronic liver disease. Patients with HPS are given extra points on the MELD score, pushing them higher up on the waiting list for liver transplantation. It’s usually recommended that patients undergo liver transplantation before their disease becomes severe.
Presently, there’s no approved medical therapy specifically for HPS. Various treatments, such as garlic, pentoxifylline, mycophenolate mofetil, aspirin, methylene blue, inhaled nitric oxide, nitric oxide inhibitors, and somatostatin, have been experimented with but none have provided sufficient benefits and have not been approved by the FDA.
A transjugular intrahepatic portosystemic shunt (TIPS), which is a procedure that creates a new connection inside the liver for blood flow, has limited data available regarding its use, and its results can vary. There are risks associated with TIPS, such as worsening of hypoxemia, as it could increase the widening and abnormal connection of blood vessels within the lungs. There’s also the threat of hepatic decompensation, a significant deterioration in liver function, and encephalopathy, a brain disorder that can happen after the procedure.
The use of pulmonary arterial coil embolization, which is a procedure to block blood flow in abnormal vessels, is limited. It can only be applied to select cases where large abnormal connections between arteries and veins are present.
What else can Hepatopulmonary Syndrome be?
When trying to diagnose Hepatopulmonary Syndrome (HPS), doctors may also look into the possibility of the following conditions as they can have similar symptoms:
- Portopulmonary hypertension (high blood pressure in the liver)
- Atelectasis (lung collapse)
- Recurrent pulmonary emboli (repeated blood clots in the lungs)
- Atrial septal defect (a hole in the wall between the heart’s upper chambers)
- Arteriovenous malformations (abnormal blood vessels connections)
- Post-pneumonectomy syndrome (condition after lung removal surgery)
- Chronic cardiopulmonary disease (long-term heart and lung disease)
- Chronic obstructive pulmonary disease (a type of lung disease)
- Pneumonitis (lung inflammation)
- Pneumonia (lung infection)
- Hepatic hydrothorax (fluid in the chest due to liver disease)
- Ascites causing reduced pulmonary functions (fluid build-up in the belly affecting lung function)
What to expect with Hepatopulmonary Syndrome
People with HPS (a condition where the liver is unable to function properly) are two times more likely to pass away than those with cirrhosis (a different liver disease) without HPS. HPS also negatively impacts the patient’s quality of life and everyday functioning.
On average, a patient with HPS has a much shorter life expectancy (about 10.5 months) compared to those with other chronic liver diseases but without HPS (about 40.8 months). The risk of mortality or death increases as the disease gets worse, and those with a very severe form of the disease face a worse prognosis or outlook.
Even after a liver transplant, survival is slightly less in those patients who had very severe HPS. This means that even after receiving a new liver, the patient’s life expectancy is less compared to people who didn’t have HPS.
Possible Complications When Diagnosed with Hepatopulmonary Syndrome
Hepatopulmonary syndrome (HPS) is a severe condition that significantly shortens the life expectancy of those suffering from liver disease. It is characterised by a continual increase in blood vessel widening and decreasing levels of oxygen in the blood. Without a liver transplant, survival is extremely difficult, given the absence of other effective medical treatments.
After a liver transplant, improved oxygen levels and a decrease in abnormal connections between arteries and veins are experienced by 80% to 85% of patients. Yet, complications can arise for some, including:
- Refractory Hepatopulmonary Syndrome: This happens when patients do not experience elevated oxygen levels or have recurring HPS after a liver transplant.
- Severe Post-Transplant Hypoxemia: This is characterised by an inability to maintain oxygen saturation levels above 85%, even with 100% oxygen supply.
- Post-Transplant Portopulmonary Hypertension: This is an unusual complication post-transplant.
Preventing Hepatopulmonary Syndrome
Doctors should check all their patients for signs of alcohol addiction and use of drugs through injections. It’s important for patients to be informed about the dangers of injecting drugs, taking too much of certain medicines like acetaminophen, and drinking too much alcohol. Help and support for overcoming these problems should be provided. People at high risk should have a check-up every year to look for signs of viral hepatitis, which is a type of liver disease.
