Hepatopulmonary Syndrome Pathophysiology

Introduction to Hepatopulmonary Syndrome

The hepatopulmonary syndrome is primarily caused by intrapulmonary vascular dilations that create a right-to-left shunt, which worsens in the upright position due to gravitational redistribution of blood flow to the lung bases where these dilations predominate, according to the European Association for the Study of the Liver 1, 2
Intrapulmonary vascular dilations are the fundamental pathological feature of hepatopulmonary syndrome, creating abnormal communications between pulmonary arteries and veins, as stated by the European Association for the Study of the Liver 1, 2

In the upright position, gravity redistributes blood flow preferentially to the lung bases, where intrapulmonary vascular dilations are more abundant, worsening the shunt and hypoxemia, as reported by the European Association for the Study of the Liver 2, 3
The upright position is the direct cause of orthodeoxia (decreased oxygenation in the upright position), according to the European Association for the Study of the Liver 1, 2

Increased release of nitric oxide in the pulmonary circulation due to increased expression and activity of two isoforms of nitric oxide synthase, as stated by the European Association for the Study of the Liver 1, 2
Activation of endothelial fractalkine (CX3CL1), a chemokine that favors the adhesion of monocytes in the pulmonary microcirculation, as reported by the European Association for the Study of the Liver 1, 2

Vascular endothelial growth factor-A (VEGF-A) produced by circulating monocytes contributes to angiogenesis, recognized as an additional pathogenic factor in hepatopulmonary syndrome, according to the European Association for the Study of the Liver 1, 2
Downregulation of miRNA-199a-5p has been described as a mechanism that contributes to the proliferation of pulmonary microvascular endothelial cells, as stated by the European Association for the Study of the Liver 1, 2

The diagnosis of hepatopulmonary syndrome requires the presence of hypoxemia (PaO₂ <80 mmHg or alveolar-arterial oxygen gradient ≥15 mmHg) and evidence of intrapulmonary vascular dilations by contrast echocardiography or pulmonary perfusion scintigraphy, as recommended by the American Association for the Study of Liver Diseases 3, 4
Pulse oximetry in the upright position (SpO₂ <96%) is highly sensitive for detecting hepatopulmonary syndrome in patients with PaO₂ <70 mmHg, according to the American Association for the Study of Liver Diseases 2, 4

Liver transplantation is the only curative treatment for hepatopulmonary syndrome, resulting in complete reversal or significant improvement in >85% of patients, as reported by the European Association for the Study of the Liver 6, 7
Five-year survival without transplantation is only 23% in patients with hepatopulmonary syndrome versus 63% in cirrhotic patients without this complication, according to the American Association for the Study of Liver Diseases 4, 7