Hepatopulmonary Syndrome

Hepatopulmonary syndrome (HPS) is the triad of liver disease (usually cirrhosis with portal hypertension), arterial hypoxaemia and intrapulmonary vascular dilatation.

Occurs in 5 to 32% of patients with cirrhosis and portal hypertension (also portal vein thrombosis, Budd Chiari).

Pathogenesis: increased pulmonary nitric oxide, endothelin B receptor activity, angiogenesis and monocyte accumulation leading to capillary dilatation (up to 60 µm), ventilation perfusion mismatch, diffusion limitation.

Severity by PaO2: mild 80 mmHg or more, moderate 60 to 80, severe 50 to 60, very severe under 50 mmHg (breathing room air, with A a gradient 15 mmHg or more, or 20 in over 64 years).

Predicts poor survival (median 24 months untreated vs 87 months without HPS); resolves in majority after liver transplantation.

• Dyspnoea, platypnoea (worse upright), orthodeoxia (PaO2 falls by 5% or 4 mmHg upright), cyanosis, clubbing, spider naevi.
• Features of chronic liver disease.
• Exclude cardiopulmonary causes.

• Pulse oximetry screening (SpO2 under 96%, supine and upright), arterial blood gas (A a gradient).
• Contrast enhanced transthoracic echocardiography (bubbles in left atrium after 3 to 6 cycles).
• Technetium 99m macroaggregated albumin lung perfusion scan: brain uptake fraction over 6%.
• Chest imaging and spirometry to exclude lung disease; echocardiography to exclude portopulmonary hypertension and intracardiac shunt.

• Liver transplantation is the only effective therapy; priority MELD exception points (MELD 22) for PaO2 under 60 mmHg. Hypoxaemia resolves in 6 to 12 months; PaO2 under 50 mmHg increases perioperative mortality.
• Oxygen supplementation for PaO2 under 60 mmHg or exertional desaturation.
• Medical therapies (limited efficacy): garlic extract, norfloxacin, methylene blue, pentoxifylline, inhaled nitric oxide synthase inhibitors, sorafenib; TIPS may improve oxygenation in selected patients.
• Coil embolisation for discrete type II (large arteriovenous communications).
• Avoid excessive diuresis, treat ascites (large volume paracentesis improves gas exchange), avoid supine posture.
• Treat cirrhosis complications; evaluate for transplant early.
• Monitor annually with pulse oximetry, blood gases.