Review article: Update on current and emergent data on hepatopulmonary syndrome

Table 1 Hepatopulmonary syndrome-diagnostic criteria

Presence of liver disease and/or portal hypertension AND

Partial pressure of oxygen < 80 mmHg or alveolar–arterial oxygen gradient [P(A-a)O2 gradient] ≥ 15 mmHg (or > 20 mmHg for patients > 65-years-old) while breathing ambient air AND

Documented intrapulmonary vascular dilatation by contrast-enhanced echocardiography or lung perfusion scanning with radioactive albumin

Table 2 Hepatopulmonary syndrome-severity classification

Mild	Alveolar-arterial oxygen gradient ≥ 15 mmHg, partial pressure of oxygen ≥ 80 mmHg
Moderate	Alveolar-arterial oxygen gradient ≥ 15 mmHg, partial pressure of oxygen ≥ 60 mmHg to < 80 mmHg
Severe	Alveolar-arterial oxygen gradient ≥ 15 mmHg, partial pressure of oxygen ≥ 50 mmHg to < 60 mmHg
Very severe	Alveolar–arterial oxygen gradient ≥ 15 mmHg, partial pressure of oxygen < 50 mmHg

Table 3 Intrapulmonary shunt quantitative classification

Contrast-enhanced echocardiography based on the number of microbubbles passing in the left ventricle
No shunt	No detection of microbubbles
Stage 1	< 30 microbubbles
Stage 2	30-100 microbubbles
Stage 3	> 100 microbubbles
Macroaggregated albumin lung perfusion
No shunt	< 6% brain uptake of radiolabeled albumin
Intrapulmonary shunt	≥ 6% brain uptake of radiolabeled albumin

Table 4 Hepatopulmonary syndrome and cardiac involvement

Study	Cirrhotic patients	Parameters assessed	Assessment tools	Associations
Karabulut et al[123]	36 without HPS	RV diastolic dysfunction	M-mode ECHO	RV diastolic dysfunction-HPS
	10 with HPS	PVR	TDI	HPS was associated with higher RV wall thickness (0.61 ± 0.13 cm vs 0.51 ± 0.10 cm) RVEDD (3.81 ± 0.38 cm vs 3.11 ± 0.94 cm)
		Systolic PAP		RA (3.96 ± 0.53 cm vs 3.58 ± 0.47 cm), systolic PAP (48.9 ± 4.8 mmHg vs 40.6 ± 5.3 mmHg)
				PVR (3.97 ± 1.31 Wood’s unit vs 3.25 ± 0.96 Wood’s unit)
Zamirian et al[124]	53 without IPS	LA dimension	M-mode ECHO	IPS was associated with higher LA dimension (4.58 ± 0.54 cm vs 3.87 ± 0.63 cm)
	39 with IPS	Cardiac output		Cardiac output (5.62 ± 0.83 L/min vs 4.75 ± 0.76 L/min)
Zamirian et al[126]	108 without HPS	LA volume	M-mode ECHO	Greater LA volume in HPS (55.1 ± 7.5 mL vs 37.1 ± 9.3 mL)
	41 with HPS			LA volume ≥ 50 mL, AUC: 0.903, sensitivity: 86.3%, specificity: 81.2%
Pouriki et al[127]	67 without HPS	Markers of LV and RV diastolic and/or systolic cardiac function	M-mode ECHO	HPS was associated with higher LVEDD (OR = 1.230, 95%CI: 1.036-1.482; P = 0.019)
	12 with HPS		TDI	S wave at left lateral wall of MV (TDI) (OR = 1.428, 95%CI: 1.049-1.943; P = 0.026)
				S wave lateral ≥ 13.5 cm/s, AUC: 0.736, sensitivity: 83.3%, specificity: 65.7%
				LVEDD ≥ 50.5 mm, AUC: 0.724, sensitivity: 75%, specificity: 68.7%
Voiosu et al[128]	57 without HPS	Association between HPS and cirrhotic cardiomyopathy	M-mode ECHO	Higher RV wall width in HPS (3.8 ± 1.2 mm vs 3.4 ± 0.6 mm)
	17 with HPS		TDI	No association between HPS and cirrhotic cardiomyopathy
				No echocardiographic measurement predictive of HPS

AUC: Area under the curve; ECHO: Echocardiography; HPS: Hepatopulmonary syndrome; IPS: Intrapulmonary shunt; LA: Left atrial; LV: Left ventricle; LVEDD: Left ventricle end diastolic diameter; MV: Mitral valve; OR: Odds ratio; PVR: Pulmonary vascular resistance; PAP: Pulmonary artery pressure; RV: Right ventricle; RVEDD: Right ventricle end diastolic diameter; TDI: Tissue Doppler imaging.