Disruption of Hepatic Sinusoidal Homeostasis Leads to Hepatopulmonary Syndrome

Hepatopulmonary syndrome (HPS) is a pulmonary vascular complication of liver disease and/or portal hypertension. HPS manifests as impaired gas exchange and hypoxemia due to intrapulmonary vascular dilatations and shunts. In response to primary liver disease, the abnormal adaptation of respiratory epithelial cells, pulmonary endothelial cells and immune cells leads to pulmonary microenvironment disequilibrium and HPS. In this review, we explore the pathophysiologic mechanisms of HPS, including vascular dilation, angiogenesis and alveolar dysfunction. The liver is the primary contributor to HPS, and liver transplantation is the only treatment that generally reverses HPS. We then discuss how disruption of hepatic sinusoidal homeostasis may impact the progression of HPS, mainly focusing on hepatocytes, cholangiocytes, LSECs and macrophages. As HPS occurs more commonly in advanced liver cirrhosis, we also discuss that normalisation of liver dysfunction and portal hypertension is crucial for the resolution of HPS. In conclusion, liver-targeted therapies may be effective in treating HPS.