What is the treatment for Hepatopulmonary Syndrome (HPS)?

Treatment for Hepatopulmonary Syndrome (HPS)

Liver transplantation is the only curative treatment for hepatopulmonary syndrome and should be considered for all patients with HPS regardless of the severity of their liver disease. 1

Definition and Diagnosis

Hepatopulmonary syndrome (HPS) is characterized by:

• Intrapulmonary vascular dilatations (IPVD) developing in the setting of portal systemic shunting 1
• Arterial hypoxemia in patients with liver disease or portal hypertension 2
• Present in 4-29% of chronic liver disease patients of all ages 1

Diagnosis requires:

• Presence of hypoxia (PaO2 <80 mmHg or alveolar-arterial oxygen gradient ≥15 mmHg while breathing ambient air) 1
• Evidence of IPVD through one of the following:
  • Contrast-enhanced transthoracic echocardiography 1
  • Technetium-labeled macro-aggregated albumin lung perfusion scan showing shunt fraction >6% 1
  • Cardiac catheterization demonstrating severe shunting 1

Treatment Options

Primary Treatment: Liver Transplantation

• Liver transplantation (LT) is the only definitive treatment for HPS, resulting in complete reversal or significant improvement in >85% of patients 1
• LT is appropriate for HPS in both cirrhotic and non-cirrhotic liver disease 1
• Five-year survival rates improved from 67% in pre-MELD era to 88% in MELD era for HPS patients undergoing transplantation 1
• HPS is considered an indication for urgent transplantation due to its poor prognosis without intervention 1
• Median survival without LT in adults with severe HPS (PaO2 <50 mmHg) is less than 12 months 1

Alternative Approaches for Specific Cases

• For patients with congenital/acquired portosystemic venous communications:
  • Closure of a congenital portosystemic shunt should be considered as an alternative to LT 1
  • Ligation of the shunt or endovascular treatment using an occlusion device may be appropriate 1

Supportive Therapy While Awaiting Transplantation

• Long-term oxygen therapy is recommended for patients with severe hypoxemia to manage symptoms 1
• Supplemental oxygen is particularly beneficial during periods of increased physical activity 1

Ineffective Medical Therapies

Multiple medical therapies have been tried with largely unsuccessful results:

• Beta-blockers, cyclooxygenase inhibitors, systemic glucocorticoids, cyclophosphamide, almitrine bismesylate, inhaled nitric oxide, and nitric oxide inhibitors have all been ineffective 1
• Pentoxifylline has shown contradictory results with frequent GI side effects 1
• Garlic administration showed some improvement in PaO2 in a small randomized study but has been associated with hepatotoxicity 1
• TIPS (transjugular intrahepatic portosystemic shunt) is not recommended for HPS treatment due to insufficient data and concerns it may enhance pulmonary vasodilation 1

Special Considerations

Transplant Prioritization

• In the US, patients with severe HPS (PaO2 <60 mmHg) receive MELD exception points to prioritize them for transplantation 1
• This policy has significantly improved post-transplant outcomes 3

Post-Transplant Course

• Important to note that respiratory function may temporarily worsen in the first days after transplantation 1
• Complete improvement and reversal of HPS may take months 1
• Patients with PaO2 <50 mmHg and no reversibility to 100% oxygen may have higher risk of irreversible respiratory failure post-transplant 1

Monitoring

• Children with portosystemic shunting should be regularly screened for HPS development with room air pulse oximetry in an upright position 1
• Hypoxemia can worsen in patients on the transplant waiting list, with a median decrease in PaO2 of 5.2 mmHg per year 1

Conclusion

While medical therapies and supportive care can help manage symptoms, liver transplantation remains the only treatment that can reverse HPS and significantly improve survival. Early diagnosis and appropriate prioritization for transplantation are essential for optimal outcomes.