What is the management for hepatopulmonary syndrome (HPS)?

Management of Hepatopulmonary Syndrome (HPS)

Liver transplantation is the only definitive treatment for hepatopulmonary syndrome, resulting in complete reversal or significant improvement in over 85% of patients with HPS. 1

Diagnosis and Assessment

• HPS is characterized by the triad of chronic liver disease, arterial deoxygenation, and widespread intrapulmonary vasodilation, occurring in 10-17% of patients with cirrhosis 2
• Diagnostic evaluation should include:
  • Arterial blood gas analysis to determine PaO2 levels and alveolar-arterial oxygen gradient 2, 3
  • Transthoracic contrast echocardiography to detect intrapulmonary vasodilation 2, 3
  • Assessment of arterial oxygen response to 100% oxygen administration 2
  • Quantification of intrapulmonary shunting using macroaggregated albumin (MAA) scan 2
• HPS severity classification based on arterial oxygen levels:
  • Mild: PaO2 ≥80 mmHg
  • Moderate: PaO2 60-79 mmHg
  • Severe: PaO2 50-59 mmHg
  • Very severe: PaO2 <50 mmHg 3

Treatment Options

Liver Transplantation

• Liver transplantation is the only curative therapy for HPS 1, 3
• HPS is considered an indication for urgent transplantation due to poor prognosis without intervention 2, 1
• Patients with severe HPS (PaO2 <60 mmHg) receive MELD exception points to prioritize them for transplantation 1, 3
• Five-year survival rates have improved from 67% in pre-MELD era to 88% in MELD era for HPS patients undergoing transplantation 1
• Important considerations for transplantation:
  • Preoperative PaO2 of 50 mmHg or less alone or combined with MAA shunt fraction of 20% or more are the strongest predictors of postoperative mortality 2
  • Respiratory function may temporarily worsen in the first days after transplantation before improvement 2, 1
  • Complete resolution of HPS may take months after transplantation 2, 1

Alternative Treatments for Non-Cirrhotic HPS

• For patients with non-cirrhotic portal hypertension causing HPS, closure of congenital portosystemic shunts should be considered as an alternative to transplantation 3, 4
• Case reports have shown HPS resolution after:
  • Transjugular intrahepatic portosystemic shunting in biliary atresia with portal hypertension 4
  • Auxiliary partial liver transplantation in Abernethy syndrome 4
  • Splenectomy in splenic vein thrombosis 4
  • Antiviral treatment in hepatitis C 4

Supportive Therapy

• Long-term oxygen therapy is recommended for patients with severe hypoxemia to manage symptoms, particularly during periods of increased physical activity 1
• Regular monitoring of oxygen saturation and arterial blood gases is essential 3

Ineffective Medical Therapies

• Multiple medical therapies have been ineffective in treating HPS, including:
  • Beta-blockers
  • Cyclooxygenase inhibitors
  • Systemic glucocorticoids
  • Cyclophosphamide
  • Almitrine bismesylate
  • Inhaled nitric oxide
  • Nitric oxide inhibitors 1
  • Somatostatin analogues 5
• Pentoxifylline has shown contradictory results with frequent GI side effects 1
• Garlic administration has been associated with hepatotoxicity 1

Prognosis

• Median survival of patients with cirrhosis and severe HPS (PaO2 <50 mmHg) is less than 12 months without transplantation 2, 1
• Five-year survival rate is only 23% in untransplanted HPS patients versus 63% in matched cirrhotic patients without HPS 3
• Survival is significantly worse in patients with HPS and PaO2 <50 mmHg at diagnosis 3
• Liver transplantation triples 5-year survival in HPS patients regardless of baseline disease severity 3

Special Considerations

• HPS can occur in patients with non-cirrhotic portal hypertension, congenital portosystemic shunts, or even acute/chronic hepatitis without significant liver dysfunction 3, 4
• Coexisting pulmonary hypertension may delay resolution of oxygen dependency after transplantation 6
• Pre-liver transplant room-air PaO2 ≤44.0 mmHg is associated with increased post-liver transplant mortality 3