Hepatopulmonary Syndrome

Definition

• Liver disease --> excessive pulmonary microvascular dilation +/- AVMs --> altered gas exchange --> hypoxemia

  • No relationship b/w severity of HPS and severity of liver disease

• Diagnostic criteria:

  • PaO2 <80 mmHg or Aa gradient >15 mmHg on room air

  • Positive contrast echocardiography or abnormal uptake in the brain with radioactive lung-perfusion scanning (see below for explanations)

  • Liver disease

Pathophysiology

Increased pulmonary vasodilatation caused by:

• Increased nitric oxide production in the lungs (no clear explanation)

• Increased lung angiogenesis factors (no clear explanation)

Mechanism of Hypoxemia

• Diffusion-perfusion limitation

  • Capillaries dilated too much --> O2 can't traverse to bind to RBC in the core of the vessel

  • If pt has elevated cardiac output --> decreased transit time in capillary bed --> even less O2 binding

  • Can be corrected w/ supplemental O2

• Ventilation-perfusion mismatch

  • Vascular dilation --> increased perfusion relative to preserved ventilation

  • If pt has atelectasis/edema/PNA --> localized hypoxic alveoli --> impaired hypoxia induced vasoconstriction due to HPS --> even more V/Q mismatch

  • Can be corrected w/ supplemental O2

• Shunts

  • HPS associated w/ pulmonary and extrathoracic AVMs --> blood flow that bypasses pulmonary capillary beds and never gets oxygenated

  • CanNOT be corrected w/ supplemental O2

Symptoms of HPS

• Dyspnea, cyanosis, clubbing

• Platypnea

  • Dyspnea in upright position that is alleviated when supine (likely due to orthodeoxia)

• Orthodeoxia

  • Hypoxemia in upright position that is alleviated when supine

  • Vascular tone remains fixed in all parts of the lung in HPS --> when upright, you decrease the surface area of gravity dependent alveolar units with better ventilation capabilities --> worse V/Q matching

Diagnosis of HPS

• Best test = transthoracic echo w/ agitated saline injected in peripheral vein

  • Bubbles are suppose to get trapped in pulmonary capillary bed because they are too big to pass through

  • In HPS, capillaries dilate --> bubbles can now pass through

  • If bubbles seen in left atrium 3 or more cardiac cycles after bubbles seen in right atrium --> intrapulmonary vascular dilation (if less than 3, could be due to intracardiac shunt)

• Pts w/ liver disease may have other lung disease that impairs gas exchange, somake sure to evaluate for:

  • Hepatic encephalopathy --> aspiration PNA

  • Emphysema from a1-AT deficiency

  • Hepatic hydrothorax (pleural effusion)

  • Atelectasis from massive ascites

  • Muscle wasting --> restrictive lung disease

  • Pulmonary HTN (entity called portopulmonary HTN)

  • Hepatic synthetic dysfunction --> PE

  • Chronic medical illness unrelated to liver disease (RAD, asthma, COPD, ILD, sarcoid, cancer, etc)

Prognosis of HPS

• Higher mortality compared to liver pts w/o HPS

  • Severe hypoxemic resp. failure is usually NOT the cause of death

  • Death from complication of liver disease (GIB, coagulopathy, sepsis, heptagonal syndrome, etc)

• Worse functional class and quality of life compared to liver pts w/o HPS

Treatment

• Supplemental O2

  • No data to confirm clinical benefit (but makes sense...)

• Pentoxifylline

  • Reduces nitric oxide synthesis

  • Clinical trials have resulted in conflicting conclusions of its benefit in HPS

• Embolization if AVM exists

• Vasodilator therapy (iNO, sildenafil) usually not used but could potentially be useful in the setting of other pulmonary disease causing VQ mismatch

• Liver transplant

  • Only proven successful treatment

  • Improves 5 year survival rate compared to no transplant

  • Hypoxia may persist or even worsen after transplant

  • Normalization of gas exchange may take 6-12 months

    • More severe pre-op hypoxia = longer time to resolution of hypoxia

References

1) Rodríguez-Roisin R, Krowka MJ. Hepatopulmonary syndrome--a liver-induced lung vascular disorder. N Engl J Med. 2008 May 29;358(22):2378-87.