Pulmonary Disorders in Cirrhosis

8/10/2019 Pulmonary Disorders in Cirrhosis

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PulmonaryHepatic vascular Disorders; R. Rodrguez-Roisin, M.J. Krowka, Ph. Herve, M.B. Fallonz, on behalf ofthe ERS Task Force; Eur Respir J 2004; 24: 861880

The hepatopulmonary syndrome; D.T. Palma, M.B.Fallon; Journal of Hepatology 45; (2006): 617625

Portopulmonary hypertension and hepatopulmonarysyndrome: a clinician-oriented overview; Mateo Porres-

Aguilar, Jose T. Altamirano, Aldo Torre-Delgadillo,Michael R. Charlton and Andres Duarte-Rojo; Eur RespirRev 2012; 21: 125, 223233


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Diagnostic criteria:

Hepatic dysfunction or portal hypertension Widened alveolar-arterial oxygen gradient (A-aPO2) (15

mmHg in patients 64 years of age) +/- hypoxemia

Intrapulmonary vasodilatation

Alveolar-arterial O2 gradient = PAO2 - PaO21.25PaCO2At sea level when breathing room air (FiO2 = 0.2), the PAO2is 150 mmHg

Above combination is so unique that it supports thediagnosis of HPS even in the presence of associated chroniccardiopulmonary diseases


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ERS Task Force staging system based on PaO2: PaO2 80 mmHg mild HPS PaO2 60-79 mmHg - moderate HPS PaO2 50-59 mmHg - severe HPS

PaO2


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Cirrhosis irrespective of aetiology (mostcommon)

Portal hypertension in the absence ofcirrhosis

Acute and chronic hepatitis in the absenceof portal hypertension

Congenital disorders without liver injury inwhich either hepatic venous blood flowdoes not reach the lung or portal venousblood reaches the IVC without passingthrough the liver


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The primary structural disturbance is diffuse orlocalised dilatation of the pulmonary pre-capillary and post-capillary vessels. Lesscommonly, pleural and pulmonary AV

communications may be present

Vasodilatation is assumed to result fromexcessive vascular production of vasodilators,particularly NO. However, the mechanism ofincreased endogenous NO production and itsrelationship to the liver disease remainsuncertain


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There are three intrapulmonary determinants ofarterial deoxygenation and all may contributeto HPS:

Alveolar V/Q mismatch (main mechanism)

due to lung regions in which alveoli arenormally ventilated but overperfused

Increased intrapulmonary shunt

Diffusion impairment of oxygen

Individual contribution by each mechanismmay varying according to HPS severity; all three

can coexist in severe and very severe HPS


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Insidious onset dyspnea (most common symptom)Early exertional dyspnoea may evolve into dyspnoea atrest as hypoxaemia progresses

Platypnea and orthodeoxia (decrease in PaO2 5% or4 mmHg from the supine to upright position)Result from a gravitational increase in blood flowthrough dilated vessels in the lung basesThe sensitivity of orthodeoxia for HPS is relatively low, but

increases in cases of severe HPSWhile orthodeoxia is observed in a variety of conditions,it is highly specific for HPS in the setting of liver disease


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Cyanosis, polycythaemia, clubbing Spider angiomata (but are frequently seen

in cirrhotic patients without HPS also)

Extrapulmonary complications of right toleft pulmonary communications, such ascerebral abscesses or ICH may occur

HPS may be an important factor thatinfluences the progression of liver disease.Mortality is usually due to complications ofhepatic disease, as opposed to a primaryrespiratory event


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Widened A-aPO2 +/- hypoxemia Pulse oximetry

A simple, non-invasive screening test for hypoxemiaCaution must be exercised in the interpretation, as pulseoximetry may overestimate oxygenation in nearly one

half of patients with cirrhosis

ABGPerformed at rest in the sitting position, while breathingroom air

In HPS, ABGs reveal an elevated age-adjusted A-aPO2with or without hypoxemiaSince patients with advanced liver disease usuallyhyperventilate, hypocapnia and respiratory alkalosis arecommon


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Intrapulmonary vasodilatation Contrast echocardiography

Transthoracic microbubble contrastechocardiography is the preferred screening test

While up to 40% of patients with cirrhosis have apositive contrast echocardiogram, only a subset ofthese patients have sufficient vasodilatation to causeabnormal gas exchange and fulfill criteria forhepatopulmonary syndrome

Transoesophageal echocardiography with contrastenhancement may be superior, being more sensitiveand with the ability to visualize the passage ofmicrobubbles through an interatrial pathway versusmicrobubble entrance into the left atrium from thepulmonary veins


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99mTc-Macroaggregated albumin scanIn the presence of shunting, a fraction of themacroaggregated albumin passes into the systemiccirculation and then, scintigraphy reveals uptake in other

organs in addition to the lung

This test allows quantification of the shunt, unlike CE-TTE.This also makes it useful in defining the contribution of HPSto gas exchange abnormalities in hypoxemic patients withboth HPS and intrinsic cardiopulmonary disease

Sensitivity of MAA scan is lower than that of CE-TTEIt is also less specific since it is not possible to differentiatebetween intracardiac and intrapulmonarycommunications


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Pulmonary angiography

Not routinely utilized since it is expensive, invasive and hasa low sensitivity for detecting intrapulmonary

vasodilatationThere are 2 types of angiographic patterns:

Type I pattern - normal angiography or diffuse vasculardilatations

Type II pattern - focal arteriovenous communications


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Liver transplantationLiver transplantation is the only establishedeffective therapy for HPSTotal resolution or significant improvementoccurs in >85% of patients. Length of time forarterial hypoxemia to normalize aftertransplantation is variable and may be >1 yearMorbidity may be higher after OLT in severe HPSThe observation that HPS increases mortality and

that transplant outcomes may worsen in casesof advanced HPS has led to the policy in UScenters of increasing priority for OLT in patientswith HPS and significant hypoxemia


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Coil embolisationIn type II HRS, arteriovenous communications areanatomically stable and may not regress after LTxand the patients may be at risk of cerebral

embolism and/or abscess. They may be amenableto treatment with coil embolisation

It has been suggested that in patients with verysevere hypoxaemia the response to 100% oxygenbreathing should be assessed, and if PaO2

improves to


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Medical therapies

There are currently no effectivemedical therapies for HPS

Rx that have been studiedaspirin,norfloxacin, garlic powder, methyleneblue


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Supportive therapies

Continuous long-term O2 therapy in

patients with PaO2


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Algorithm: Mild HPS (PaO2 80 mmHg) ABG should be

measured at least once a year to detect anyabnormal PaO2 change and if symptoms appear

Moderate HPS (PaO2 60-79 mmHg) - ABG should bemeasured at least once a year to detect anyabnormal PaO2 change and if symptoms appear. IfPaO2 progressively deteriorates in a symptomaticpatient, then OLT can be considered

Severe HPS (PaO2 50-59 mmHg) - consideration ofOLT is vital Very severe HPS (PaO2


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Diagnostic criteria:

Portal hypertension with or without hepaticdisease

PAHmPAP 25 mmHg at rest with anormal / decreased pcwp (240 dyn/s/cm5 (>3 Wood units)


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Staging based on mPAP at rest:

mPAP 25-34 mmHg - mild PPHTN

mPAP 3544 mmHg - moderate PPHTN

mPAP 45 mmHg - severe PPHTN

Presence or severity of portopulmonaryhypertension does not appear to correlatewith the severity of underlying liver disease orseverity of portal hypertension


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Vasoconstriction and obstruction in thesmall pulmonary arteries occur due to dueto intimal and medial smooth muscleproliferation and fibrosis and in situthrombosis

Increase in vasoconstrictor and

vasoproliferative substances (e.g. ET-1,serotonin) and decrease in vasodilatorsubstances (e.g. NO, prostacyclin) mediatein these processes


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Imbalances in the factors occur as a result of: Increased blood flow in chronic liver disease causes

pulmonary vascular wall shear stress, which can triggerthe dysregulation of numerous mediators

Portosystemic shunts and defective hepatic

metabolism may allow the shunting of vasoactivesubstances from the splanchnic to the pulmonarycirculation

Portosystemic shunts and decreased phagocyticcapacity of the liver, allow circulating bacteria andbacterial endotoxins from the gastrointestinal tract to

enter the pulmonary circulation. This causes recruitmentof pulmonary interstitial macrophages which whenactivated, release numerous factors


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Other supportive Ix

CXR - enlarged central pulmonary arterieswith peripheral pruning, RA and RV

enlargement ECGP pulmonale, RVH, RAD, RBBB

ABG - may show mild-to-moderatehypoxaemia, increased AaPO2 anddecreased PaCO2

Pulmonary function tests - reduced DLCO

BNP - marker of right ventricular stress


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Important distinctions in PPHTN managementcompared to idiopathic PAH: Oral anticoagulation is traditionally not

recommended due to the increased risk of

gastrointestinal hemorrhage CCBs are contraindicated as they canproduce mesenteric vasodilation that canworsen portal hypertension and asresponders are few

Beta blockers are associated withdeterioration of exercise capacity andpulmonary hemodynamics due to theirnegative inotropic and chronotropic effects


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Life style measures

Avoid activities that impose heavyphysical stress and valsalva manoeuvre

Stop smoking Avoid high altitudes

Reduce dietary salt intake

Avoid pregnancy


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Supportive therapy Diuretics - reduce RV volume overload, reduce

hepatic congestion, relieve peripheral edema

Overdiuresis should be avoided as this will

further reduce the RV output Continuous long-term O2 therapy in patients with

PaO2


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Specific therapyHave been studied in PPHTN to some extentbut mostly extrapolated from their use in

idiopathic PAH

Phosphodiesterase-5 Inhibitors (e.g. sildenafil)

Endothelin Receptor Antagonists ( bosentan,sitaxentan, ambrisentan)Risk of transaminitis is present; could beconsidered more safely in extrahepatic portalhypertensionBosentan has been used safely in ChildPughclass A cirrhosis


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Balloon atrial septostomy / RV assistdevice

Indicated as a palliative procedure ifconventional measures fail


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HPS PPHTN

Clinical features Cyanosis, clubbing No cyanosis

Evidence of PHT and RVF

ECG None RBBB

RAD

RVHABG Moderate-to-severe hypoxaemia No/mild hypoxaemia

CXR Normal Cardiomegaly

Hilar enlargement

CEE Always positive Usually negative (unless ASD /

PFO exist)

99mTcMAA shunting index 6%


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Pulmonary Disorders in Cirrhosis