Hepatopulmonary Syndrome and Associated Pulmonary Complications

Hepatopulmonary syndrome (HPS) arises in the context of advanced liver disease and portal hypertension, manifesting as an intrapulmonary vascular dilatation that impairs arterial oxygenation. Pathophysiological drivers include increased production of vasoactive mediators such as nitric oxide and carbon monoxide, dysregulated angiogenesis, and alveolar epithelial dysfunction, all leading to ventilation–perfusion mismatch and hypoxaemia. Beyond hypoxaemia, HPS may evolve or coexist with other pulmonary complications, notably portopulmonary hypertension and acute lung injury after surgical interventions such as transjugular intrahepatic portosystemic shunting. Clinical consequences range from breathlessness and reduced exercise tolerance to poorer outcomes on liver‐transplant waiting lists. Timely recognition and mechanistic insight have informed novel diagnostic screening and paved the way for targeted therapies that seek to modulate oxidative stress, autophagy and endothelial proliferation.

Research from Nature Portfolio

Recent investigations have revealed a central role for autophagy in the pulmonary microvascular alterations of experimental HPS. In rodent models induced by common bile duct ligation, autophagy is upregulated in pulmonary microvascular endothelial cells, promoting excessive cell proliferation and vessel dilatation. Pharmacological inhibition of autophagy markedly attenuates vascular remodelling, reduces pulmonary oedema and improves arterial oxygenation. These findings position autophagy as a promising therapeutic target to reverse pulmonary microvascular pathology in HPS.

Hepatopulmonary Syndrome and Associated Pulmonary Complications publication trend

The graph below shows the total number of articles in hepatopulmonary syndrome and associated pulmonary complications across all publications each year (not limited to Nature Index journals).

Technical terms

Hepatopulmonary syndrome (HPS): A condition characterised by liver disease, intrapulmonary vascular dilatation and arterial hypoxaemia.

Intrapulmonary vascular dilatation (IPVD): Abnormal widening of pulmonary blood vessels leading to right‐to‐left shunting of blood.

Transjugular intrahepatic portosystemic shunt (TIPS): A radiological procedure creating a channel between portal and systemic circulation to reduce portal pressure.

Autophagy: A cellular process of self‐degradation that regulates organelle turnover and influences cell proliferation.

Malondialdehyde: A lipid peroxidation by‐product used as a biomarker of oxidative stress.

Alveolar–arterial oxygen gradient (AaDO2): The difference between alveolar and arterial oxygen partial pressures, indicating gas exchange efficiency.

References

1. Oxidative stress as one of the pathogenetic mechanisms of hepatopulmonary syndrome in patients with liver cirrhosis. Gastroenterology (2024).
2. High Prevalence and Clinical Relevance of Intrapulmonary Vascular Dilatations in Patients Undergoing TIPS Implantation. Clinical Gastroenterology and Hepatology (2024).
3. Hepatopulmonary syndrome in patients with porto-sinusoidal vascular disorder: Characteristics and outcome. JHEP Reports (2024).
4. Inhibition of autophagy ameliorates pulmonary microvascular dilation and PMVECs excessive proliferation in rat experimental hepatopulmonary syndrome. Scientific Reports (2016).