Role of bubble contrast echocardiography in the diagnosis of hepatopulmonary syndrome

Monika R1*, Jenifer M.L2

1Echo Technician, Kauvery Hospital, Alwarpet, Chennai, Tamil Nadu

2Assistant Manager, Department of Echocardiography, Kauvery Hospital, Alwarpet, Chennai, Tamil Nadu

*Correspondence

Abstract

Hepatopulmonary syndrome (HPS) is an underdiagnosed pulmonary vascular complication of chronic liver disease characterized by the triad of liver dysfunction, arterial hypoxemia, and intrapulmonary vascular dilatation. Early recognition is crucial as liver transplantation remains the only definitive therapy. We report a case of decompensated chronic liver disease with portal hypertension and unexplained hypoxemia, in which bubble contrast echocardiography played a pivotal diagnostic role in confirming Hepatopulmonary syndrome.

Key words: Hepatopulmonary syndrome (HPS); Liver dysfunction; Hypoxemia,

Introduction

Hepatopulmonary syndrome is an important but often underdiagnosed cause of hypoxaemia in patients with chronic liver disease. It is defined by the presence of liver dysfunction, abnormal arterial oxygenation and Intrapulmonary vascular dilatation The prevalence of HPS among patients with cirrhosis ranges from 10% to 30%, with higher rate observed in those undergoing evaluation for liver transplantation. Patient frequently present with dyspnoea and hypoxia that cannot be fully explained by intrinsic cardiac or pulmonary disease. This article presents a case of suspected Hepatopulmonary syndrome evaluated using bubble contrast echocardiogram and integrated the pathophysiology mechanism described in the literature to explain the clinical and echocardiographic findings.[2]

Case Presentation

A 47-year-old female patient with known history of decompensated chronic liver disease presented with progressive breathlessness, portal hypertension with hepatitis C reactive. Clinical findings of abdominal distention, ascites, reduced urine output, clubbing nails and Spider angioma (spider naevus) – a small red spot with thin blood vessels spreading out like spider legs.

Her vital are stable, Chest X ray, ECG and 2D echo shows normal finding, CT Abdomen contrast shows? Budd chiris syndrome with liver Cirrhosis. Her Liver function test has increased total bilirubin count of 2.66 mg/ dl. And reduced albumin of 2.9 g/ dL. Despite of supportive management, the patient continued to exhibit oxygen desaturation that was disproportionate to findings on routine evaluation. Given the unexplained hypoxia in the setting of chronic liver disease a bubble contrast echocardiogram was required to evaluate for a Right to left shunt.

Echocardiographic Evaluation Using Bubble Contrast Study

The primary exposure to bubble contrast echo has been in the evaluation of suspected intracardiac shunt. Though, this case provides a valuable learning opportunity in recognising the diagnostic significance of bubble contrast in patient with complex systemic disease.

The bubble echo was performed using a 10ml agitated saline injected through a peripheral vein. The agitated saline is a combination of 8 ml of normal saline and 2 ml of air. The agitated saline is passed between two 10ml leur lock syringe via a three-way connector. The initial opacification of the right atrium and right ventricle was observed, followed by delayed appearance of microbubbles in the left atrium after 3rd cardiac cycle. The microbubbles transfer within 3 cycles through left atrium refer to as Intracardiac shunt, if there is a delay microbubble transfer between 4th to 6th cycle is referred as extracardiac or Intrapulmonary shunt The Intrapulmonary shunt is graded according to the microbubbles, via less than 5 grade I, 5 to 20 microbubbles grade II, morethan 20 microbubbles grade III. However, her bubble contrast echocardiogram shows a positive Intrapulmonary/Extracardiac shunt with grade III Opacification, suggestive of Hepatopulmonary Syndrome.

Pathophysiology of HPS

The pathophysiology of HPS is complex and involves abnormal pulmonary vasodilation and angiogenesis within the pulmonary microcirculation.  In patient with chronic liver disease, hepatic injury led to increased production and impaired clearance of vasoactive substances.

Experimental and clinical studies have demonstrated that endothelin 1 plays a central role by stimulating endothelin -B receptors in pulmonary endothelial cells, resulting in regulation of endothelial nitric oxide synthase and increased nitric oxide products.

Excess nitric oxide cause marked pulmonary vasodilation, particularly within the precapillary and capillary vessels. This leads to ventilation -perfusion mismatch a diffusion limitation. As oxygen must travel a greater distance to equilibrate with the red blood cells. In addition, bacterial translocation from the gut in cirrhotic patient activates pulmonary intravascular macrophages, further increasing nitric oxide synthase. These mechanisms collectively result in functional Right to Left shunt.

Pulmonary angiogenesis has also been implicated in HPS, with studies demonstrate increased vascular endothelial growth factors signalling and capillary proliferation. These structural and functional changes explain the delayed passage of microbubbles through the pulmonary circulation observed on contract echocardiogram.

Difference between Hepatopulmonary Syndrome and Porto Pulmonary Hypertension

Image Source: Way Seah Lee, MD et al. The Journal of Pediatrics, 2018

Hepatopulmonary syndrome (HPS) and portal hypertension are two distinct complications of chronic liver disease that affect different vascular systems and have different clinical and diagnostic implications. Portal hypertension results from increased resistance to blood flow within the cirrhotic liver, leading to elevated pressure in the portal venous system. This manifests clinically as ascites, splenomegaly, and the development of portosystemic collaterals such as esophageal and perisplenic varices. In contrast, Hepatopulmonary syndrome is characterized by abnormal pulmonary vascular dilatation secondary to liver dysfunction, causing intrapulmonary shunting and impaired oxygenation. Patients with HPS typically present with hypoxemia, dyspnea, and characteristic platypnea–orthodeoxia, rather than features of raised portal pressure. From a diagnostic perspective, portal hypertension is identified through imaging and endoscopic findings, while Hepatopulmonary syndrome is confirmed by arterial blood gas analysis and a positive bubble contrast echocardiography showing delayed appearance of microbubbles in the left heart (after 3–6 cardiac cycles), indicating intrapulmonary shunting. Importantly, portal hypertension alone does not produce a positive contrast echo; positivity occurs only when Hepatopulmonary syndrome coexists. Thus, while both conditions arise in the setting of chronic liver disease, portal hypertension represents a portal venous pressure disorder, whereas Hepatopulmonary syndrome is a pulmonary vascular complication with significant implications for oxygenation and transplant prognosis.[3]

FeaturePorto Pulmonary HypertensionHepatopulmonary Syndrome
Primary system involved Portal venous circulation Pulmonary vascular system
Underlying mechanisms Increased intrahepatic vascular resistance due to Cirrhosis Pulmonary capillary dilatation and intrapulmonary shunting due to liver dysfunction
Main haemodynamic changes Elevated portal venous pressureAbnormal pulmonary vasodilatation
Typical clinical features Ascites, splenomegaly, varicesDyspnea, hypoxemia, platypnea–orthodeoxia
Oxygenation status Usually, normal Reduced PaO₂ with widened A–a gradient
Cause of symptoms Venous congestion in portal systemImpaired gas exchange
Role of Porto systemic collateral Present and prominent Not responsible for hypoxemia
Bubble contrast echocardiogram Usually, Negative Positive with delayed bubbles (4–6 cardiac cycles)
Timing of bubbles appearance in LANo appearance Delayed appearance
ABG Findings Usually, normal Hypoxemia
Chest X rayUsually, normal Usually, normal
Definitive treatment TIPS, medical therapy, liver transplantationLiver transplantation (curative)
Prognostic implicationChronic but manageableIndicates advanced disease, affects transplant priority

Discussion

Hepatopulmonary syndrome (HPS) is a well-recognized pulmonary vascular complication of chronic liver disease and is defined by the triad of underlying liver dysfunction, arterial hypoxemia, and intrapulmonary vascular dilatation. In the present case, the patient with decompensated chronic liver disease (Child–Pugh class B) and features of portal hypertension developed hypoxemia secondary to Hepatopulmonary syndrome. While portal hypertension explains the presence of ascites and splenomegaly, it does not directly account for hypoxemia, which in this patient was attributable to intrapulmonary shunting associated with HPS. Contrast-enhanced echocardiography demonstrated delayed appearance of microbubbles in the left cardiac chambers, confirming intrapulmonary vascular dilatation and supporting the diagnosis.[1]

Management of Hepatopulmonary syndrome is largely supportive. Long-term oxygen therapy is recommended to alleviate hypoxemia and improve functional capacity and quality of life. Optimization of underlying liver disease, including treatment of hepatitis C virus infection and prevention of further hepatic decompensation, is essential. However, no pharmacological therapy has been shown to reliably reverse intrapulmonary vascular dilatation. Liver transplantation remains the only definitive treatment proven to correct hypoxemia and improve long-term survival in patients with HPS. Therefore, early recognition of Hepatopulmonary syndrome using contrast echocardiography is crucial to facilitate timely referral for transplant evaluation. This case highlights the importance of considering HPS in cirrhotic patients presenting with unexplained hypoxemia and reinforces the diagnostic and prognostic value of bubble contrast echocardiography in guiding clinical management. [3,4,9]

Conclusion

HPS should be suspected in patient with chronic liver disease and disproportionate hypoxia. Bubble contrast echocardiogram is a sensitive, non-invasive diagnostic tool for detecting Intrapulmonary shunting and plays a central role in the evaluation of suspected HPS. Understanding the underlying pathophysiology helps to correlate echocardiographic findings with clinical presentation and support timely referral for definitive management.

References

  • Rodríguez-Roisin R, Krowka MJ. Hepatopulmonary syndrome A liver-induced lung vascular disorder. N Engl J Med. 2008;358(22):2378–2387.
  • Fallon MB, Abrams GA. Pulmonary dysfunction in chronic liver disease. Hepatology. 2000;32(4):859–865.
  • Krowka MJ, Fallon MB, Kawut SM, et al. International liver transplant society practice guidelines: Diagnosis and management of hepatopulmonary syndrome and portopulmonary hypertension. Transplantation. 2016;100(7):1440–1452.
  • Abrams GA, Jaffe CC, Hoffer PB, Binder HJ, Fallon MB. Diagnostic utility of contrast echocardiography and lung perfusion scan in patients with hepatopulmonary syndrome. Gastroenterology. 1995;109(4):1283–1288.
  • Vedrinne JM, Duperret S, Bizollon T, et al. Comparison of transthoracic and transesophageal contrast echocardiography for detection of intrapulmonary vascular dilatation in liver disease. Chest. 1997;111(5):1236–1240.
  • Fallon MB, Mulligan DC, Gish RG, et al. Model for end-stage liver disease (MELD) exception for hepatopulmonary syndrome. Hepatology. 2006;44(2):439–446.
  •  Gupta S, Castel H, Rao RV, et al. Improved survival after liver transplantation in patients with hepatopulmonary syndrome. Am J Transplant. 2010;10(2):354–363.

Additional References

  • Grace JA, Angus PW. Hepatopulmonary syndrome: update on recent advances in pathophysiology, investigation, and treatment. J Gastroenterol Hepatol. 2013;28(2):213–219.
  • Offer J, Green L, Houghton AR, Campbell J. A case of hepatopulmonary syndrome. J Med Case Reports. 2015;9:123.

 

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