What is the management and treatment of hepatopulmonary syndrome?

Management and Treatment of Hepatopulmonary Syndrome

Liver transplantation is the only definitive and curative treatment for hepatopulmonary syndrome (HPS), with complete reversal or significant improvement in more than 85% of patients with severe hypoxemia. 1

Diagnosis and Screening

• HPS should be suspected in patients with chronic liver disease who present with tachypnea, polypnea, digital clubbing, and/or cyanosis 1, 2
• Diagnostic criteria include:
  • Pulse oximetry in upright position (SpO₂ <96% is highly sensitive for HPS) 1, 2
  • Arterial blood gas analysis showing PaO₂ <80 mmHg or alveolar-arterial oxygen gradient (P[A-a]O₂) ≥15 mmHg on room air (≥20 mmHg in patients ≥65 years) 1, 2
  • Contrast-enhanced (microbubble) echocardiography to document intrapulmonary vascular dilatations 1
  • Technetium-labeled macroaggregated albumin (MAA) lung perfusion scan showing shunt fraction >6% can be used as an alternative 1, 2

Medical Management

• Long-term oxygen therapy is recommended for symptom management in patients with severe hypoxemia, though data on effectiveness, tolerance, cost-effectiveness, and survival impact are limited 1
• No established effective medical therapies exist for HPS 1, 3
• Multiple attempted pharmacological interventions have shown disappointing results:
  • Beta-blockers, cyclooxygenase inhibitors, systemic glucocorticoids, cyclophosphamide, almitrine bismesylate, inhaled nitric oxide, nitric oxide inhibitors, and antimicrobial agents have been uniformly unsuccessful 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 potential for hepatotoxicity 1

Liver Transplantation

• Liver transplantation is the only definitive treatment for HPS 1, 2, 3
• HPS is considered an indication for urgent liver transplantation due to its poor prognosis without intervention 1
• Five-year survival rate is only 23% in untransplanted HPS patients versus 63% in matched cirrhotic patients without HPS 1, 2
• Median survival in adults with severe HPS (PaO₂ <50 mmHg) is less than 12 months without transplantation 1, 2
• After implementation of the MELD exception policy, five-year survival after transplantation improved from 67% in the pre-MELD era to 88% in the MELD era 1
• Patients with severe hypoxemia (PaO₂ <50 mmHg) have increased perioperative mortality but should still be considered for transplantation 1

Special Considerations

• For non-cirrhotic causes of HPS (e.g., congenital portosystemic shunts), closure of the shunt should be considered as an alternative to transplantation 1, 2
• TIPS (transjugular intrahepatic portosystemic shunt) has been proposed to reduce portal pressure in HPS, but data are insufficient and there is concern it may exacerbate pulmonary vasodilation 1
• Coil embolization of dilated pulmonary arteries may be considered as a palliative treatment for patients with diffuse type I HPS who are not transplant candidates 4
• In critically ill patients with HPS in the ICU, careful monitoring for worsening hypoxemia is essential 1

Monitoring

• Regular assessment of hypoxemia severity is recommended for patients on the transplant waiting list, as PaO₂ can decrease by approximately 5.2 mmHg per year 1
• Patients with portosystemic shunting should be regularly screened for HPS development with room air pulse oximetry in an upright position 1
• Assessment of functional capacity and oxygen requirements during physical activity should be performed regularly 2

Prognosis

• Without transplantation, HPS carries a poor prognosis, with significantly worse outcomes in patients with PaO₂ <50 mmHg 1, 2
• Liver transplantation triples 5-year survival in HPS patients regardless of baseline disease severity 2
• Hypoxemia typically worsens in the first days after transplantation due to the surgical procedure itself, and improvement may take months 1