Hepatopulmonary syndrome differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Soroush Seifirad, M.D.[2]

Overview

Hepatopulmonary syndrome (HPS) must be differentiated from portopulmonary hypertension (PPH) and hereditary hemorrhagic telangiectasia (HHT).

Differentiating Hepatopulmonary Syndrome from other Diseases

Mild hypoxemia occurs in 30 percent of patients with chronic liver disease. It may be due to common cardiopulmonary diseases such as congestive heart failure, chronic obstructive pulmonary disease (COPD) or pneumonia. Pulmonary vascular bed malfunction also might be responsible for certain conditions such as Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPH).

Hepatopulmonary syndrome (HPS) must be differentiated from portopulmonary hypertension (PPH) and hereditary hemorrhagic telangiectasia (HHT).

Portopulmonary hypertension is often confused with HPS. However, HPS and PPH are not the same disease. Although both are abnormalities of the pulmonary vasculature resulting from liver disease, HPS is characterized by vasodilatation and hypoxemia whereas PPH is characterized by obstruction or narrowing (vasoconstriction) of blood vessels with resulting pulmonary arterial hypertension.

Differentiating hepatopulmonary syndrome from other diseases on the basis of pulse oximetry, arterial blood gas (ABG) analysis , contrast enhanced echocardiography; 99mTc scan: lung perfusion scintigraphy with technetium 99mTc labeled macro aggregated albumin, chest CT scan , pulmonary angiography, and pulmonary function test.

On the basis pulse oximetry, arterial blood gas (ABG) analysis, contrast enhanced echocardiography, 99mTc scan (lung perfusion scintigraphy with technetium 99mTc labeled macro aggregated albumin), chest CT scan , pulmonary angiography, and pulmonary function test, hepatopulmonary syndrome (HPS) must be differentiated from portopulmonary hypertension (PPH) and hereditary hemorrhagic telangiectasia (HHT).

Diseases	Clinical manifestations					Para-clinical findings							Gold standard	Additional findings
	Symptoms			Physical examination
						Lab Findings			Imaging			Histo pathology
	Respiratory symptoms	Chronic liver disease symptoms	Platypnea	Orthodeoxia	Chronic liver disease signs	Pulse oximetry	Arterial blood gas (ABG) analysis	Pulmonary function test	Chest CT scan/ Pulmonary angiography	99mTc scan	Contrast enhanced echocardiography
HSP	+	+ (in most of the patients)	+	+	+ (in most of the patients)	SaO2<96%	15 mmHg ≤ AaPO2 PaO2< 80 mm Hg	Diffusion impairment Decreased DLCO Reduced lung volumes	Frequently nonspecific and subtle Dilated peripheral pulmonary vessels Increased pulmonary artery to bronchus ratios Characteristic findings of intrapulmonary vascular dilatations Direct arterio-venous communications may be less commonly seen.	+	+ (could distinguish between intracardiac and intrapulmonary shunt) In intracardiac shunting: three cardiac cycles after the appearance of the bubbles in the right heart chambers. In intrapulmonary shunting: four to six cardiac cycles after the appearance of the bubbles in the right heart chambers.	Plays no role in diagnosis	Triad of liver disease ABG (widened alveolar-arterial oxygen gradient Intra-pulmonary vascular dilation or arterio-venous communications that result in a right-to-left intrapulmonary shunt.	N/A
PPH	+ Dyspnea Fatigue Syncope.	+	-	-	+	Hypoxemia	Used for Pulmonary hypertension Class Identification PaO2 is normal or only slightly lower than normal PaCO2 is decreased as a result of alveolar hyperventilation	PFT cannot distinguish PPH from other pulmonary disorders with diffusion impairment Decreased diffusion capacity	Central pulmonary artery dilatation Abrupt narrowing or tapering of peripheral pulmonary vessels Right ventricular hypertrophy Right ventricular and atrial enlargement Dilated bronchial arteries	-	- Right heart dysfunction secondary to pulmonary hypertension Diagnosis and staging is based on the followings: Pulmonary artery pressure >25 mmHg Pulmonary capillary wedge pressure<15 mmHg Pulmonary vascular resistance >240syn·s·cm−5		The diagnosis of portopulmonary hypertension is based on hemodynamic criteria: Portal hypertension and/or liver disease (clinical diagnosis—ascites/varices/splenomegaly) Mean pulmonary artery pressure—MPAP > 25 mmHg at rest Pulmonary vascular resistance—PVR > 240 dynes s cm−5 :Pulmonary artery occlusion pressure— PAOP < 15mmHg or transpulmonary gradient—TPG > 12 mmHg where TPG = MPAP − PAOP.	N/A
HHT	+	-			-	SaO2<96%	Shunt in favor of AVM					TGFβ signalling pathway impairment Arteriovenous malformations (AVMs) in various internal organs	Hereditary hemorrhagic telangiectasia is a clinical diagnosis that is based on the presence of three of four criteria (i.e., epistaxis, telangiectasias, visceral arteriovenous malformations, or family history of the disease)	Spontaneous recurrent epistaxis Multiple teleangiectasias on typical locations (see above) Proven visceral AVM (lung, liver, brain, spine) First-degree family member with HHT
Diseases						Lab 1	Lab 2	Lab 3	Imaging 1	Imaging 2	Imaging 3	Histopathology	Gold standard	Additional findings
Differential Diagnosis 4
Differential Diagnosis 5
Differential Diagnosis 6

• Platypnea (increased shortness of breath when the body is in a vertical position) and orthodeoxia (3-10 mmHg reduction in РаО2 in capillary blood during transition from horizontal to vertical position)

• 99mTc scan: lung perfusion scintigraphy with technetium 99mTc labeled macro aggregated albumin

• Chronic liver disease symptoms including, Itching, easy bruising, abdominal fullness, decreased libido, abdominal distension, and fatigue.
• Chronic liver disease signs including spider angioma, red palms, edema, gynecomastia
• Respiratory symptoms including shortness of breath, clubbed fingers, and cyanosis.
• Hepatopulmonary syndrome (HPS) must be differentiated from portopulmonary hypertension (PPH) and hereditary hemorrhagic telangiectasia (HHT).
• Severity of HPS is defined based on PaO2, while below 50 is extremely sever, 50-60 is sever, and more than 60 is defined as moderate to mild.