Hepatopulmonary syndrome: pathophysiological mechanisms and clinical implications

Hepatopulmonary syndrome (HPS) is a complication of liver disease that affects up to 30% of patients with cirrhosis and portal hypertension and is associated with a more than doubled risk of mortality. This narrative review aims to summarize the pathophysiology and management of HPS, while highlighting indications, timing, and outcomes of liver transplantation as the sole curative therapy.

While supplemental oxygen therapy and pharmacological strategies help alleviate symptoms of HPS, including dyspnea, platypnea, orthodeoxia, and fatigue imposed on signs of liver dysfunction, transplantation remains the sole curative approach. Liver transplantation triples 5-year survival in HPS patients irrespective of baseline disease severity. While data on the correlation between arterial partial pressure of oxygen-based disease severity stages and pretransplant waitlist mortality remain equivocal, the introduction of a model for end-stage liver disease exception points has prompted improved posttransplant survival in these patients. Animal studies provide evidence for pharmacological treatment including norfloxacin or methylene blue, however, large-scale trials targeting humans are lacking.

While future studies are warranted to investigate the efficacy of medical and interventional treatment options for HPS, liver transplantation remains the only curative therapy. Transplantation demonstrates excellent outcomes independent of disease severity, while optimal timing requires an individualized approach.