What are the treatment options for hepatopulmonary syndrome (HPS)?

Treatment Options for Hepatopulmonary Syndrome

Liver transplantation is the only definitive treatment for hepatopulmonary syndrome (HPS) that has been proven effective, resulting in complete reversal or significant improvement in more than 85% of patients. 1

Diagnosis and Classification

Before discussing treatment options, it's important to understand the diagnostic criteria for HPS:

• HPS is characterized by the clinical triad of:

  • Chronic liver disease
  • Arterial deoxygenation
  • Widespread intrapulmonary vasodilation 1

• Diagnostic tests include:

  • Arterial blood gas analysis
  • Contrast-enhanced echocardiography
  • Assessment of liver disease/portal hypertension
  • Calculation of alveolar-arterial oxygen gradient 2

• Severity classification based on PaO2:

  • Mild-to-moderate: PaO2 60-80 mmHg
  • Severe: PaO2 < 60 mmHg 2

Treatment Algorithm

1. Medical Management

• Long-term oxygen therapy:

  • Recommended for patients with severe hypoxemia (PaO2 < 60 mmHg)
  • Provides symptomatic relief but does not alter disease progression 1

• Pharmacological treatments:

  • No established effective medical therapy is currently available

  • Multiple agents have been tried with uniformly unsuccessful results:

    • Beta-blockers
    • Cyclooxygenase inhibitors
    • Systemic glucocorticoids
    • Cyclophosphamide
    • Almitrine bismesylate
    • Inhaled nitric oxide
    • Nitric oxide inhibitors
    • Antimicrobial agents 1

  • Pentoxifylline has shown contradictory results in small pilot studies with frequent GI side effects 1

  • Garlic administration showed improvement in PaO2 in a small randomized study but has been associated with hepatotoxicity 1

2. Interventional Approaches

• Transjugular Intrahepatic Portosystemic Shunt (TIPS):

  • Insufficient data to support its use
  • Concerns that TIPS may enhance pulmonary vasodilation by exacerbating hyperkinetic circulation
  • No recommendation can be made for TIPS in HPS treatment 1

• Coil embolization (embolotherapy):

  • May temporarily improve arterial oxygenation in patients with angiographic arteriovenous communications
  • Not a definitive treatment 1

3. Liver Transplantation

• The definitive treatment for HPS:

  • Results in complete reversal or significant improvement in >85% of patients with severe hypoxemia 1
  • Reverses HPS through closure of intrapulmonary shunts 1
  • Should be considered for patients with HPS and PaO2 < 60 mmHg 1

• Prioritization for transplantation:

  • Patients with HPS and PaO2 < 60 mmHg can receive enhanced prioritization for organ allocation 1
  • In the US, MELD exception points are assigned to patients with severe HPS 1

• Monitoring while awaiting transplantation:

  • Arterial blood gas analysis should be performed every six months
  • Hypoxemia can worsen in patients on the transplant list (median decrease in PaO2 of 5.2 mmHg per year) 1
  • Pre-LT room-air PaO2 ≤44.0 mmHg is associated with increased post-LT mortality 1

Special Considerations

• Perioperative management:

  • Expect deterioration of respiratory function in the first days after liver transplantation
  • Improvement and reversibility of HPS may take months 1
  • Patients with PaO2 < 50 mmHg and no reversibility to 100% oxygen may have increased perioperative mortality 1

• Post-transplant management:

  • Inhaled nitric oxide, methylene blue, extracorporeal membrane oxygenation, and non-invasive ventilation may improve oxygenation immediately post-transplant 1
  • Five-year survival rate after liver transplantation has improved from 67% in the pre-MELD era to 88% in the MELD era 1

Pitfalls and Caveats

• Severe hypoxemia (PaO2 < 45-50 mmHg) is associated with increased post-transplant mortality 1

• Preoperative PaO2 ≤ 50 mmHg alone or in combination with a MAA shunt fraction of ≥ 20% are the strongest predictors of postoperative mortality 1

• The median survival of patients with cirrhosis and severe HPS is less than 12 months without transplantation 1

• Spontaneous resolution of HPS is uncommon 1

• Regular assessment of hypoxemia severity is crucial to facilitate transplantation before very severe hypoxemia occurs 1