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Hepatopulmonary Syndrome

Hepato Pulmonary Syndrome

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


Presentation

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 [1]. 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.

Hepatic findings that can accompany HPS include cirrhosis, pulmonary hypertension, acute liver failure and ischemic hepatitis [9].

Hypoxemia
  • There was a trend toward an increased risk of developing this complication in patients with very severe preoperative hypoxemia, defined as a partial pressure of arterial oxygen   50 mm Hg (8/41 with very severe hypoxemia versus 3/49 without severe hypoxemia[ncbi.nlm.nih.gov]
  • 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.[symptoma.com]
  • He has not experienced worsening hypoxemia or dyspnea and has not developed PAVMs.[ncbi.nlm.nih.gov]
  • He had full regression of hypoxemia at 3 months after a transcatheter shunt closure. These results indicate that CEPS may present in children with unexplained hypoxemia, which may lead to devastating clinical consequences.[ncbi.nlm.nih.gov]
  • Increased biliary complications in hepatopulmonary syndrome (HPS) have been hypothesized due to post-transplant hypoxemia.[ncbi.nlm.nih.gov]
Marfanoid Habitus
  • Based on these results and the clinical background a diagnosis of hepatopulmonary syndrome with Marfanoid habitus was made. Patient was treated conservatively as he was not prepared for liver transplantation.[ncbi.nlm.nih.gov]
Dyspnea
  • In cases that underwent liver transplantation, dyspnea and hypoxia improved, but pulmonary fibrosis subsequently developed. CONCLUSIONS: This report identifies HPS as a frequent cause of dyspnea in telomerase and telomere gene mutation carriers.[ncbi.nlm.nih.gov]
  • Interestingly, six months after LT, and in the absence of dyspnea, a new CEE showed persistent passing of bubbles to the left cavities.[ncbi.nlm.nih.gov]
  • Here, we discuss a case of a 45-year-old male Indian patient with no medical history who presented to our hospital with exertional dyspnea, hypoxia, and classical signs of HPS.[ncbi.nlm.nih.gov]
  • Dyspnea and hypoxemia are worse in the upright position (which is called platypnea and orthodeoxia, respectively).[en.wikipedia.org]
  • Pulse oximetry is recommended in patients presenting with platypnea whereas arterial blood gases (ABG) test should be performed in patients with severe resting dyspnea.[symptoma.com]
Clubbed Finger
  • She had been suffered from progressive liver failure with dyspnea, clubbing fingers, and cyanosis. Preoperative arterial blood gas analysis revealed severe hypoxia (arterial O2 tension of 54.5 mmHg and O2 saturation of 84.2%).[ncbi.nlm.nih.gov]
  • The physical examination revealed clubbed fingers and collateral veins. The patient had an increased alveolar-arterial oxygen gas tension difference. The levels of anti-mitochondrial antibody (AMA) and AMA M2 was 80 times normal.[ncbi.nlm.nih.gov]
  • The major clinical manifestations are arterial hypoxemia, clubbed fingers and spider navei. Orthodeoxia and platypnea are usual clinical features. A simple non invasive method to screen HPS is desirable.[ncbi.nlm.nih.gov]
Dysphagia
  • His wide-ranging research interests include the immunohistochemistry and genetic analysis of premalignant esophageal cancers, the role of neuropeptides at the LES and other GI sphincters, dysphagia, esophageal reflux disease and gastrointestinal hormones[med.upenn.edu]
Cyanosis
  • The third patient was a 4-year-old male with a 3-year history of cyanosis and decreased exercise tolerance. He had full regression of hypoxemia at 3 months after a transcatheter shunt closure.[ncbi.nlm.nih.gov]
  • We report the case of a 5-year-old child with dyskeratosis congenita who presented cyanosis and dyspnea at exertion. He had severe hypoxemia with elevated alveolar-arterial oxygen gradient in the setting of liver disease.[ncbi.nlm.nih.gov]
  • The most obvious clinical finding is hypoxemia along with bluish discoloration of the skin (cyanosis).[symptoma.com]
  • An eight-year-old girl was evaluated for unexplained cyanosis. A contrast echo was suggestive of pulmonary arteriovenous fistula. Further evaluation revealed Abernethy malformation (type 2) leading to hepatopulmonary syndrome.[ncbi.nlm.nih.gov]
  • A six-year-old boy presented with cough, cyanosis and clubbing. Investigations revealed hypoxia (PaO2 53 mm Hg on room air) which was only partially correctable (PaO2 73 mm Hg) with 100% oxygen administered through a non re breathing face mask.[ncbi.nlm.nih.gov]
Joint Effusion
  • Hypertrophic osteoarthropathy is an uncommon disease in the pediatric age group characterized by noninflammatory joint effusions, terminal digit clubbing, and radiographic evidence of periosteal new bone formation affecting the hands, feet, and distal[ncbi.nlm.nih.gov]
Meningism
  • A patient with an unusual series of uncommon sarcoidosis complications, including cirrhosis with HPS, brain abscess and finally Nocardia meningitis, is reported.[ncbi.nlm.nih.gov]

Workup

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.

Pulse oximetry is recommended in patients presenting with platypnea [10] whereas arterial blood gases (ABG) test should be performed in patients with severe resting dyspnea.

Contrast echocardiography is another important diagnostic tool [11] 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

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 [12]. Prophylactic use of antimicrobials is recommended to reduce the level of severeness in HPS [13].

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 [14].

Prognosis

HPS is a consequence of an ineffectively treated chronic liver disease. Due to this fact, the prognosis in HPS is considered to be poor. A liver transplantation has proven to result in a good clinical outcome [8].

Etiology

The definite etiology of HPS is not known [3] although it has been found to develop in patients already suffering from a chronic liver disease (e.g. cirrhosis), portal hypertension, isolated portal hypertension and hepatitis [4].

Epidemiology

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% [5]. HPS may affect patients of all age groups.

Sex distribution
Age distribution

Pathophysiology

As already described, pulmonary disease in HPS is accompanied by two common manifestations that comprise pulmonary vasodilatation and hypoxemia.

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 [6]. 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 [7].

Prevention

Prevention of HPS remains unknown due to a lack of scientific data on the exact etiology of the disease.

Summary

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 [1]. 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 [2].

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.

Patient Information

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 excessively increased product of natural vasodilator called nitrous oxide (NO) accounts for the abnormally increased intrapulmonary vascular dilatation in HPS.

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.

References

Article

  1. Rodriguez-Roisin R, Krowka MJ, Hervé P, Fallon MB. Pulmonary-hepatic vascular disorders (PHD). Eur Respir J. 2004; 24:861-880.
  2. Aller R, Moya JL, Avila S, et al. Implications of estradiol and progesterone in pulmonary vasodilatation in cirrhotic patients. J Endocrinol Invest. 2002;25:4-10.
  3. Abrams GA, Jaffe CC, Hoffer PB, et al. Diagnostic utility of contrast echocardiography and lung perfusion scan in patients with hepatopulmonary syndrome. Gastroenterology. 1995;109:1283–1288.
  4. Regev A, Yeshurun M, Rodriguez M, et al. Transient hepatopulmonary syndrome in a patient with acute hepatitis A. J Viral Hep. 2001;8:83–86.
  5. AUKrowka MJ, Cortese DA. Hepatopulmonary syndrome. Current concepts in diagnostic and therapeutic considerations. Chest. 1994; 105(5):1528.
  6. Cremona G, Higenbottam TW, Mayoral V et al. Elevated exhaled nitric oxide in patients with hepatopulmonary syndrome. Eur Respir J. 1995;8:1883–1885.
  7. Rabiller A, Nunes H, Lebrec D et al. Prevention of gramnegative translocation reduces the severity of hepatopulmonary syndrome. Am J Respir Crit Care Med. 2002;166:514–517.
  8. Fallon MB, Mulligan DC, Gisch RG, et al. Model for end-stage liver disease (MELD) exception for hepatopulmonary syndrome. Liver Transpl. 2006;12:105-107.
  9. Fuhrmann V, Madl C, Mueller C, et al. Hepatopulmonary syndrome in patients with hypoxic hepatitis. Gastroenterology. 2006;131:69-75.
  10. Abrams GA, Sanders MK, Fallon MB. Utility of pulse oximetry in the detection of arterial hypoxemia in liver transplant candidates. Liver Transpl. 2002;8:391–396.
  11. Abrams GA, Jaffe CC, Hoffer PB, et al. Diagnostic utility of contrast echocardiography and lung perfusion scan in patients with hepatopulmonary syndrome. Gastroenterology 1995;109:1283-1288.
  12. Garcia-Tsao G: Portal hypertension. Curr Opin Gastroenterol. 2005;21:313–322.
  13. Rabiller A, Nunes H, Lebrec D, et al. Prevention of gram-negative translocation reduces the severity
    of hepatopulmonary syndrome. Am J Respir Crit Care Med. 2002;166:514–517.
  14. Lange PA, Stoller JK. The Hepatopulmonary Syndrome. effect of liver transplantation. Clin Chest Med 1996;17:115–123.

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Last updated: 2019-07-11 20:40