What is hepatopulmonary syndrome (HPS)?

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From the Guidelines

Hepatopulmonary syndrome (HPS) is a serious complication of liver disease characterized by intrapulmonary vascular dilatations, resulting in hypoxemia, and can only be cured by liver transplantation (LT) 1.

Definition and Pathophysiology

HPS occurs when liver dysfunction causes blood vessels in the lungs to dilate abnormally, creating a mismatch between ventilation and perfusion. This results in oxygen-poor blood bypassing the lungs' air sacs and entering the systemic circulation.

Clinical Presentation

Patients with HPS typically experience:

  • Shortness of breath, particularly when standing or sitting (platypnea)
  • Low oxygen levels that worsen in an upright position (orthodeoxia)
  • Spider-like blood vessels on the skin
  • Finger clubbing

Diagnosis

Diagnosis involves:

  • Measuring blood oxygen levels
  • Contrast echocardiography to detect shunting
  • Pulmonary angiography in some cases
  • Calculating the alveolar-arterial oxygen gradient 1

Treatment

The definitive treatment for HPS is liver transplantation, which can reverse the condition in many patients 1. Supplemental oxygen may provide symptomatic relief while awaiting transplant. However, there is no established medical therapy currently available for HPS, and several drugs have been applied with conflicting results 1.

Prognosis

The severity of HPS is not related to the severity of liver disease, and it can be an isolated indication for LT 1. Patients with PaO2 <50 mmHg and no reversibility to 100% oxygen may have a risk of irreversible respiratory failure in the post-transplant period and a high risk of perioperative mortality 1.

From the Research

Definition and Characteristics of Hepatopulmonary Syndrome

  • Hepatopulmonary syndrome (HPS) is a pulmonary vascular complication of liver disease, characterized by intrapulmonary vascular dilatations and shunts, resulting in impaired gas exchange 2.
  • It is defined by an alveolar-arterial gradient > 15 mm Hg measured at sea level, and is seen in 15 to 30% of cirrhotic patients 3.
  • HPS is attributable to an intrapulmonary vascular dilatation that may induce severe hypoxemia, and is a pulmonary complication observed in patients with chronic liver disease and/or portal hypertension 4.

Pathogenesis and Diagnosis

  • The key event in the pathogenesis of HPS is the development of intrapulmonary vascular dilatation (IPVD), which has been linked to increased pulmonary levels of nitric oxide 3.
  • A complex interaction between the liver, the gut, and the lungs, predominately impacting pulmonary endothelial cells, immune cells, and respiratory epithelial cells, is responsible for the development of typical pulmonary alterations seen in HPS 2.
  • Pulse oximetry is a useful screening test for HPS, which can guide subsequent use of arterial blood gases, and contrast-enhanced transthoracic echocardiography is the most effective test to demonstrate IPVD 3.

Treatment and Prognosis

  • Liver transplantation is the only therapeutic option and generally reverses HPS, resulting in complete resolution or significant improvement in gas exchange in over 85% of patients 3.
  • No medical therapy is established as effective for HPS, although treatment with inhaled Treprostinil has been shown to improve oxygenation in some cases 5.
  • The presence of HPS increases mortality and impairs quality of life, but is reversible with liver transplantation 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Hepatopulmonary syndrome.

JHEP reports : innovation in hepatology, 2022

Research

Hepatopulmonary syndrome.

Seminars in respiratory and critical care medicine, 2012

Research

Hepatopulmonary Syndrome.

Digestive diseases and sciences, 2015

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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