What is the diagnostic workup for hepatopulmonary syndrome?

Diagnostic Workup for Hepatopulmonary Syndrome

The diagnostic workup for hepatopulmonary syndrome (HPS) should include pulse oximetry screening, arterial blood gas analysis, contrast echocardiography, and macroaggregated albumin lung perfusion scan to confirm the triad of liver disease, arterial oxygenation abnormalities, and intrapulmonary vascular dilations. 1, 2

Initial Screening and Suspicion

• HPS should be suspected in patients with chronic liver disease who present with tachypnea, polypnea, digital clubbing, and/or cyanosis 1
• Pulse oximetry in the upright position is the recommended screening tool for HPS in adults (not in pediatric patients) 1, 3
• A pulse oximetry reading <96% has 100% sensitivity and 88% specificity for detecting patients with PaO2 <60 mmHg 3
• A threshold value of ≤94% can detect all patients with PaO2 <60 mmHg with increased specificity of 93% 3

Diagnostic Criteria

• HPS diagnosis requires the presence of three components: 2

  • Liver disease or portal hypertension
  • Intrapulmonary vascular dilations (IPVD)
  • Arterial oxygenation abnormalities

• For patients with SpO2 <96%, arterial blood gas (ABG) analysis should be performed 1

• Diagnostic criteria include PaO2 <80 mmHg and/or alveolar-arterial oxygen gradient (P[A-a]O2) ≥15 mmHg while breathing ambient air 1

• For adults ≥65 years, a P[A-a]O2 ≥20 mmHg cut-off should be used 1, 2

Confirmation of Intrapulmonary Vascular Dilations

• Contrast-enhanced (microbubble) echocardiography is the recommended test to characterize HPS 1, 2

  • Appearance of saline bubbles in the left atrium within 3-6 cardiac cycles confirms intrapulmonary shunting 1

• Trans-esophageal contrast-enhanced echocardiography can be performed to definitively exclude intra-cardiac shunts, though this technique carries risks 1

• Technetium-99m macroaggregated albumin (MAA) lung perfusion scan should be performed: 1, 2

  • As a complementary tool to quantify the degree of shunting in patients with severe hypoxemia and coexistent intrinsic lung disease
  • To assess prognosis in patients with HPS and very severe hypoxemia (PaO2 <50 mmHg)
  • A shunt fraction >6% is diagnostic of significant intrapulmonary shunting 2

Advanced Imaging

• Pulmonary angiography should be performed only in patients with severe hypoxemia (PaO2 <60 mmHg) poorly responsive to 100% oxygen administration, and when there is strong suspicion of arteriovenous communications amenable to embolization 1

• Chest radiographs in HPS usually show bibasilar nodular or reticulonodular opacities 4

• Conventional CT can show that these opacities represent dilated lung vessels, while high-resolution CT is useful in excluding pulmonary fibrosis or emphysema 4

Severity Classification

• HPS is classified based on severity of hypoxemia: 2
  • Mild: PaO2 ≥80 mmHg
  • Moderate: PaO2 60-79 mmHg
  • Severe: PaO2 50-59 mmHg
  • Very severe: PaO2 <50 mmHg

Prognostic Implications

• Patients with HPS have significantly worse outcomes compared to cirrhotic patients without HPS 2
• Five-year survival rate is only 23% in untransplanted HPS patients versus 63% in matched cirrhotic patients without HPS 1, 2
• Survival is significantly worse in patients with HPS and PaO2 <50 mmHg at diagnosis 1
• Preoperative PaO2 ≤44 mmHg alone or in combination with a MAA shunt fraction of 20% or more are the strongest predictors of postoperative mortality 1

Pitfalls and Caveats

• Neither contrast echocardiography nor MAA scan can definitively differentiate discrete arteriovenous communications from diffuse precapillary and capillary dilatations or cardiac shunts 1
• HPS can occur in patients with non-cirrhotic portal hypertension, congenital portosystemic shunts, or even acute/chronic hepatitis without significant liver dysfunction 2
• HPS can be an isolated indication for liver transplantation, as it is the only curative treatment 1, 2
• The severity of HPS is not related to the severity of liver disease 5