Introduction:
Hepatopulmonary syndrome (HPS) is the common cause of respiratory insufficiency in patients with chronic liver disease. When the liver is not functioning properly, the blood vessels in the lungs may get dilated. The severity of this condition results in the failure of the lungs to effectively transfer oxygen to the body. This is referred to as hepatopulmonary syndrome. It is commonly seen in patients with scarring of the liver.
What Are the Signs and Symptoms of Hepatopulmonary Syndrome?
Many people do not present with symptoms. If symptoms occur, these include:
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Shortness of breath, particularly when sitting or standing.
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Spider angioma (broken or dilated blood vessels under the skin.)
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Cyanosis (bluish discoloration of the lips and skin.)
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Clubbing of the fingers or toes.
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The most common symptom is platypnea (breathlessness in an upright position which is improved with lying down (supine) position.)
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Orthodeoxia (decrease in the partial pressure of oxygen when moving from supine to upright position. The severity increases with the severity of hepatopulmonary syndrome.)
What Are the Causes of Hepatopulmonary Syndrome?
1. The cause of hepatopulmonary syndrome is most commonly associated with portal hypertension due to chronic liver disease or cirrhosis.
2. Hypoxemia in hepatopulmonary syndrome occurs commonly due to limitations to the movement of oxygen from the lungs into the bloodstream and also due to the mismatching ratio between air moving through the lungs and blood moving into the lungs (ventilation-perfusion mismatch) - Caused as a result of intrapulmonary vascular dilatation (IVPD).
3. Autopsy reports in hepatopulmonary syndrome patients suggest that small blood vessels in the lungs are severely enlarged or dilated. These dilations are due to increased production or impaired liver clearance of chemicals that cause blood vessels to relax, or decreased production of chemicals causes blood vessels to contract.
4. During this process, the release of nitric oxide (NO) at the level of pulmonary blood vessels is found to be a key factor in causing the dilation of blood vessels.
5. The nitric oxide is released through several pathways, such as gut bacterial translocation -inflammation caused by bacteria and bacteria material escaping from the gut into the blood circulation in patients with cirrhosis. This results in the recruitment of macrophages to the pulmonary blood vessels, where nitric oxide is produced.
6. Hence, these nitric oxide-mediated changes in pulmonary blood vessel size result in structural changes in the blood vessels called vascular remodeling.
7. Based on the location of dilated pulmonary blood vessels, hepatopulmonary syndrome is grouped under two categories:
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Type 1 Hepatopulmonary Syndrome- Type 1 hepatopulmonary occurs more commonly than type 2 hepatopulmonary syndrome. It is characterized by diffuse pulmonary vasodilatations at the precapillary levels close to the site of gaseous exchange of the lungs.
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Type 2 Hepatopulmonary Syndrome - The type 2 hepatopulmonary lesions are more discrete and localized dilatations. In addition, they are significant arteriovenous communications located at a distance from the site of gaseous exchange. Therefore, supplemental oxygen therapy can be done in case of type 1 hepatopulmonary syndrome. However, the therapy cannot be done in the case of type 2 hepatopulmonary syndrome because of its poor response to oxygen and true anatomical shunting.
What Are the Complications of Hepatopulmonary Syndrome?
Hepatopulmonary syndrome is a fatal disease that reduces the lifespan of patients with liver complications. Majority of patients present with progressive vasodilation and severe hypoxemia. Death without liver transplantation is inevitable, as no other medical therapies are available.
Post liver transplantation reports improved oxygenation and decreased arteriovenous shunts in 80 to 85 % of patients. However, some patients may develop complications.
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Severe post-transplant hypoxemia is a failure to maintain oxygen saturation above 85 %, even to 100 %.
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Refractory hepatopulmonary syndrome, in this case, patients fail to improve oxygenation or develop recurrent hepatopulmonary syndrome after liver transplantation.
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Post-transplant portopulmonary hypertension rarely occurs.
What Is the Diagnostic Approach for Hepatopulmonary Syndrome?
1. Imaging Tests- The evidence for liver disease is examined through abdominal imaging for liver abnormalities, including cirrhosis.
2. Blood Tests- These are taken to reveal the biochemical evidence of synthetic liver dysfunction, including albumin, bilirubin, and international normalized ratio (INR), to provide evidence for cirrhosis.
3. Echocardiogram- An echocardiogram is also known as cardiac ultrasound, a technique that uses sound waves to take images of the heart. In hepatopulmonary patients, a small amount of salt water is injected into a vein in the arm. It helps to evaluate whether the blood vessels in the lungs are dilated - a typical symptom of hepatopulmonary syndrome.
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2-D transthoracic agitated saline contrast echocardiography test is used to identify intrapulmonary vascular dilation.
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Saline microbubbles of size 15 to 180 micrometers are created by mixing 10 ml of normal saline with 10 ml of air injected intravenously during transthoracic echocardiography. In the absence of intrapulmonary vascular dilation, the bubbles appear in the right-sided chamber of the heart and are trapped in the pulmonary capillary bed and get absorbed.
4. Macroaggregated Albumin Lung Perfusion Scan- A technetium -99 labeled macro aggregated albumin total body scan (MAA scan) is helpful to evaluate the extent to which hepatopulmonary syndrome is contributing to a patient's oxygenation abnormalities. A small number of radioactive particles called Technetium 99 (Tc99m)- macro aggregated albumin is injected into the patient's arm, and then a specialized camera is used to locate the buildup of particles. This is one of the most specific techniques to evaluate the presence and severity of dilated blood vessels in the lungs.
5. Computed Tomography (CT) of the Chest- This test is carried out to rule out the other abnormalities involved in causing abnormal oxygenation. Though pulmonary blood vessels are dilated, this scan cannot distinguish hepatopulmonary syndrome from liver disease without hepatopulmonary syndrome.30 (HPS.30).
Review visits include a pulmonary function test, an oxygen titration study, a six-minute walk test, and an arterial blood gas to evaluate disease progression.
What Are the Treatment Approaches for Hepatopulmonary Syndrome?
1. Oxygen Therapy-
It is recommended in patients with severe hypoxemia. It is provided until a more definitive treatment, such as liver transplantation, can be carried out. An increase in oxygenation and reduction in hypoxia results in better exercise tolerance and well-being of life.
2. Liver Transplantation-
Liver transplantation is the only treatment of choice for long-term survival benefits for patients with hepatopulmonary syndrome. This improves hypoxemia in 6 to 12 months. Reports have shown that partial pressure of oxygen and alveolar-arterial (A-a) gradient reverses rapidly within a span of six months. There is an evident reversal of intrapulmonary shunts, but it may take longer than six months.
3. Transjugular Intrahepatic Portosystemic Shunt (TIPS)-
This can aggravate the hyperkinetic circulatory state - increasing intrapulmonary vasodilation and worsening hypoxemia. There is also the risk of hepatic decompensation and encephalopathy after a transjugular intrahepatic portosystemic shunt.
4. Pulmonary Arterial Coil Embolization-
It can only be used in selected cases with large arteriovenous communications.
Conclusion:
Prompt diagnosis and timely management with an early liver transplant are the only way to alter the course of this disease. An interprofessional team approach involving pulmonologists, hepatologists, transplant surgeons, and addiction medicine specialists is required to manage patients with hepatopulmonary syndrome.
