Hepatopulmonary syndrome

(HPS)
Juan I. Irizarry
Medical Intern
Hospital San Cristobal
Epidemiology
• General Prevalence (Cirrhosis and/or portal hypertension)
• 4 – 47%
• Variable thresholds in alveolar-arterial gradient are responsible for this high variance in
province
• Variability in evaluating pulmonary vascular dilation also contributes to the variance
• Patient Profiles
• Cirrhotic - 15%
• Chronic viral hepatitis (Including with and without cirrhosis) - 10%
• Budd-Chiari syndrome - 28%
• No correlation between the severity of liver disease and HPS
• Male predilection (Cirrhosis is more common in males)
Key Hepatopulmonary Syndrome Concepts
• A pulmonary disorder that results as a complication of liver disease or
more commonly portal hypertension.
• Characterized by the following triad (as per the Revised criteria)
• Chronic Liver Disease
• Pulmonary vascular dilation
• Gas exchange abnormalities in absence of other causes of impaired
pulmonary function.
Pathophysiology
• Key disease pathology is dilation of pulmonary capillaries
• Due to imbalance of vasodilators and vasoconstrictors
• Liver disfunction → ↑ macrophages (bacterial translocation from the
intestine and endotoxemia) → Production of inflammatory mediators (TNF-α)
→ ↑ N.O. (pulmonary vasodilation)
• Bacterial accumulation + ↑ N.O. → Heme oxygenase activity → Degradation
of heme → production of CO (pulmonary vasodilator)
• Causes mismatched ventilation perfusion (too much blood for one
alveoli) and decreased diffusion capacity (too much blood in the
vessel for oxygen to diffuse adequately). These lead to hypoxemia and
the symptomology.
• Angiogenesis
• Again the inflammatory response → ↑ TNF-α → Vascular endothelial growth
factor activation (VGEF) → Angiogenesis
 Presentation
• Asymptomatic
• In cases of mild hypoxia/A-a disturbance; Majority of diagnosed patients are asymptomatic
• Dyspnea
• Most frequent symptom but very non-specific for HPS (eg, hydrothorax, portopulmonary HTN
• Platypnea
• Pathognomonic. Opposite of orthopnea (which can also be a sign)
• Orthodeoxia
• Patient desaturates when they are upright, >5% or >4mmHg
• Spider angioma
• Notable finding due to sharing the same pathophysiology as HPS
• Digital Clubbing
• PPV of 75% for HPS (*still not specific)
• Signs of CLD are neither sensitive or specific: weakness, fatigue, anorexia, ascites,
organomegaly, jaundice asterixis, anasarca, caput medusae, gynecomastia, testicular
atrophy, varices…
Diagnosis
Grading Severity
• Mild → PaO2 >80mmHg on room air
• Moderate → PaO2 >60mmHg and <80mmHg on room air
• Severe → PaO2 >50mmHg and <60mmHg on room air
• Very severe → PaO2 <50mmHg on room air or PaO2 <300mmHg on
100% O2
Treatment
• Liver transplantation
• The only effective treatment, some can have complete resolution
• Improves survival rates (5 year approximately 76%) *similar to non-HPS Liver
transplant patients
• Oxygen therapy in patient with severe hypoxia
• More studies needed to have data on its effect on the disease course or
patient
• Although many pharmacologic substances have been tried, non have
demonstrated substantial enough results to warrant
recommendation.
Prognosis
• Not enough studies to provide a confident general result
• For the same reasons stated in prevalence (variable thresh
• Some have reported  41% mortality over an approximate 2.5-year
period 
• Other studies comparing survival rates between HPS and non-HPS
cirrhosis showed HPS with a worse 5 year survival (23% vs 63%)
Review
• A common complication of cirrhosis that should be considered as
playing a role in cirrhotic patients with dyspnea or cyanosis.
• Presumed to be do to a pulmonary vasculature imbalance leading to
hypoxia as a result of liver disease
• The only effective treatment is Liver transplantation