How is hepatopulmonary syndrome (HPS) classified?

Classification of Hepatopulmonary Syndrome

Hepatopulmonary syndrome (HPS) is classified based on the severity of hypoxemia, with four categories determined by arterial oxygen levels: mild (PaO2 ≥80 mmHg), moderate (PaO2 60-79 mmHg), severe (PaO2 50-59 mmHg), and very severe (PaO2 <50 mmHg). 1

Diagnostic Criteria for HPS

HPS is diagnosed based on a triad of components:

1. Presence of liver disease or portal hypertension 1, 2

   • Can occur in cirrhotic and non-cirrhotic portal hypertension
   • May also develop with congenital portosystemic shunts or even acute/chronic hepatitis without significant liver dysfunction

2. Intrapulmonary vascular dilatations (IPVD) 1, 2

   • Documented by contrast-enhanced echocardiography (most sensitive test)
   • Alternatively, technetium-labeled macroaggregated albumin (MAA) scan showing shunt fraction >6%

3. Arterial oxygenation abnormalities 1

   • PaO2 <80 mmHg on room air OR
   • Alveolar-arterial oxygen gradient (P[A-a]O2) ≥15 mmHg (≥20 mmHg in patients ≥65 years)

Severity Classification

HPS severity is classified into four categories based on arterial oxygen levels: 1, 2

• Mild: PaO2 ≥80 mmHg
• Moderate: PaO2 60-79 mmHg
• Severe: PaO2 50-59 mmHg
• Very severe: PaO2 <50 mmHg

This classification is clinically important as it directly correlates with prognosis and treatment decisions, particularly regarding liver transplantation prioritization.

Clinical Implications of Classification

The severity classification has significant implications for:

1. Prognosis 1, 3

   • Five-year survival rate is only 23% in untransplanted HPS patients versus 63% in matched cirrhotic patients without HPS
   • Survival is significantly worse in patients with HPS and PaO2 <50 mmHg at diagnosis

2. Transplantation priority 1, 3

   • Patients with severe HPS (PaO2 <60 mmHg) should be evaluated for liver transplantation
   • MELD exception points are granted to patients with severe HPS to prioritize them for transplantation

3. Post-transplant outcomes 1, 4

   • Pre-LT room-air PaO2 ≤44.0 mmHg is associated with increased post-LT mortality
   • Patients with very severe hypoxemia (PaO2 <50 mmHg) have higher risk of developing severe post-operative hypoxemia

4. Monitoring requirements 1

   • Arterial blood gas analysis should be performed every six months in patients with HPS to monitor disease progression
   • Median decrease in PaO2 is approximately 5.2 mmHg per year

Screening and Diagnostic Approach

For patients with liver disease or portal hypertension: 1, 5

• Initial screening: Pulse oximetry (SpO2 <96% has 100% sensitivity and 88% specificity for detecting HPS)
• Confirmatory testing:
  • Arterial blood gas analysis to determine PaO2 and P(A-a)O2
  • Contrast-enhanced echocardiography to document IPVD
  • MAA scan to quantify degree of shunting in patients with severe hypoxemia or coexistent intrinsic lung disease

Clinical Pearls

• HPS should be suspected in patients with liver disease who present with unexplained dyspnea, tachypnea, digital clubbing, or cyanosis 1, 2
• The severity classification directly impacts treatment decisions, with liver transplantation being the only definitive treatment 3, 6
• Regular monitoring is essential as HPS has a progressive course with worsening hypoxemia over time 1, 7
• Patients with severe HPS (PaO2 <60 mmHg) should be prioritized for liver transplantation evaluation as it significantly improves survival 1, 3