How is hepatopulmonary syndrome diagnosed and treated?

Diagnosis and Treatment of Hepatopulmonary Syndrome

Hepatopulmonary syndrome (HPS) is definitively diagnosed by the presence of hypoxia and intrapulmonary vascular dilatations in patients with liver disease or portal hypertension, and liver transplantation is the only curative treatment option with significant improvement in survival. 1, 2, 3

Diagnostic Criteria

• HPS should be suspected in patients with chronic liver disease who present with symptoms such as tachypnea, digital clubbing, and/or cyanosis 2

• Diagnosis requires the following criteria:

  • Presence of liver disease or portal hypertension 1
  • Hypoxia with 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
  • Evidence of intrapulmonary vascular dilatations (IPVD) 1

• Initial screening should be performed with:

  • Room air pulse oximetry in upright position (SpO2 <96% is highly sensitive for HPS) 2
  • Regular screening is recommended for all patients with portosystemic shunting associated with cirrhotic or noncirrhotic portal hypertension 1

• Confirmatory testing requires one of the following to demonstrate IPVD:

  • Contrast-enhanced transthoracic echocardiography (most sensitive test showing microbubble opacification of left heart chambers 3-6 cycles after right atrial passage) 1, 2
  • Technetium-labeled macro-aggregated albumin lung perfusion scan showing shunt fraction >6% 1, 2
  • Cardiac catheterization demonstrating severe shunting of IPVD 1

Treatment Options

• Liver transplantation is the only definitive treatment for HPS, resulting in complete reversal or significant improvement in >85% of patients 2, 3

• Liver transplantation triples 5-year survival in HPS patients regardless of baseline disease severity 2

• Five-year survival rates have improved from 67% in pre-MELD era to 88% in MELD era for HPS patients undergoing transplantation 3

• HPS is considered an indication for urgent transplantation due to its poor prognosis without intervention 3

• For non-transplant candidates or while awaiting transplantation:

  • Supplemental oxygen therapy is recommended for patients with hypoxemia, particularly during periods of increased physical activity 1, 3
  • 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

• Medical therapies that have been tried but shown to be ineffective include:

  • Beta-blockers, cyclooxygenase inhibitors, systemic glucocorticoids 3
  • Cyclophosphamide, almitrine bismesylate, inhaled nitric oxide 3
  • Pentoxifylline (contradictory results with frequent GI side effects) 3
  • Garlic (associated with hepatotoxicity) 3

Prognostic Factors

• Median survival in adults with severe HPS (PaO2 <50 mmHg) without transplantation is less than 12 months 1, 3
• Five-year survival rate is only 23% in untransplanted HPS patients versus 63% in matched cirrhotic patients without HPS 2
• Patients with severe HPS (PaO2 <60 mmHg) receive MELD exception points to prioritize them for transplantation 3

Special Considerations

• HPS can occur in patients without evidence of liver dysfunction (e.g., congenital hepatic fibrosis, portal vein thrombosis) 1
• Respiratory function may temporarily worsen in the first days after transplantation, but complete improvement and reversal of HPS may take months 3
• HPS is present in 4-29% of chronic liver disease patients of all ages 1
• If HPS is present prior to initiating management for portal hypertension, the clinical features may worsen 1

Monitoring

• Regular screening with room air pulse oximetry in upright position is recommended for patients with portal hypertension 2
• Assessment of functional capacity and oxygen requirements during physical activity should be performed regularly 2