Pulmonary complications of hepatic diseases

Table 1 Pulmonary hypertension; drug classification

Classification	Name	Mechanism of action
Endothelin receptor antagonist	Bosentan	Dual ETA and ETB receptor subtypes antagonist. Specifically, inhibition of ET-1 receptors
	Ambrisentan	Highly selective ETA receptor inhibition
	Macitentan	High affinity ETA than ETB antagonist.
Phosphodiesterase 5 inhibitors	Sildenafil	High selectivity for PD5 vs PD2, 3 and 4.
	Tadalafil	High selectivity for PD5 compared with PD1, 4, 7 and 10.
Prostanoids	Epoprostenol	Synthetic prostacyclin with potent effects of vasodilatation and platelet aggregator inhibitor.
	Treprostinil	Long acting tricyclic benzindene synthetic analogue of prostacyclin. Vasodilator and inhibits platelet inhibition.

Table 2 Differences between the hepatopulmonary syndrome and portopulmonary hypertension

	Hepatopulmonary syndrome	Portopulmonary hypertension
Pathophysiology	Severe vasodilatation	Severe vasoconstriction
	Production of endothelin-1 and tumor necrosis alpha and eNOS and iNOS	Concentric intimal fibrosis, and smooth muscle hyperplasia and hypertrophy
	Increase of CO	Endothelin-1, prostacyclin and thromboxane
	Vasculoendothelial growth factor-A
	Angiogenesis
Clinical features	Most patients are asymptomatic	Dyspnea
	Dyspnea	Orthopnea
	Platypnea	Fatigue
	Orthodeoxia	Syncope
	Significant sleep-time oxygen desaturation	Chest pain
		Lightheadedness
		Tricuspid regurgitation murmur, with a pronounced P2 sound
		Increased jugular venous pressure
		Peripheral edema
		Ascites
Diagnosis	Corrected alveolar-arterial oxygen gradient (Abnormal if > 15-20 mmHg) with or without hypoxemia (PaO2), all in sitting position	Transthoracic echocardiography.
	Contrast-enhanced echocardiography
	Degree of severity: Alveolar-Arterial oxygen gradient > 15 mmHg,mild with PaO2 > 80 mmHg, moderate > 60 mmHg to < 80 mmHg, severe > 50 mmHg to < 60 mmHg or very severe < 50 mmHg
	Pulmonary angiography
Treatment	Liver transplant	Endothelin receptor antagonist, phosphodiesterase type-5inhibitors, prostanoids, and combination therapy
		Sildenafil alone or combined with prostacyclins
		Transjugular intrahepatic portosystemic shunting
		Liver transplant

eNOS: Endothelial nitric oxide synthase; CO: Carbon monoxide; NO: Nitric oxide.