DiagnosingandManagingPortalHypertension,AscitesandVariceal

Hemorrhage

FredPoordad,MD

CirrhosisNormal

Nodules Irregularsurface

Nodulessurroundedbyfibroustissue

GrossandMicroscopicImageofaNormalandaCirrhoticLiver

PrevalenceofCirrhosis• Theprevalenceofcirrhosis,bothworldwideandintheUS,isunknown1• Cirrhosisisanoutcomeofavarietyofcauses;underlyingcauseiscommonlyusedforsurveillancepurposes2

• Compensatedcirrhosisoftengoesundetectedforprolongedperiodsoftime1

• Expertsestimatethat5.5millionpeopleintheUnitedStateshavecirrhosis3

1.Schuppan D,AfdhalNH.Lancet 2008;371(9615):838-8512.Available athttp://pubs.niaaa.nih.gov/publications/surveillance83/Cirr05.htm.3.Khungar V,PoordadF,Clin Liver Dis2012;16:73-89

PortalHypertension

Increased Resistance(Architectural changessecondary to fibrous tissueformation; active vasoconstrictiondue to decrease in formationof endogenous NO)

Increased Blood Flow(Splanchnic arteriolar vasodilation )

Increased Portal Pressure• Shunting (encephalopathy)• Increased salt and water retention (ascites)• Variceal formation (bleeding)

AdaptedfromGarcia-Tsao G,etal.Hepatology.2007;46:922-938.

• Consequencesofportalhypertensionproducesymptoms:• Gastroesophagealvarices• Ascites• Enlargedspleen• Hepaticencephalopathy

PortalHypertension

From: http://www.merck.com/mmhe/sec10/ch135/ch135d.html. Accessed 09/09/15

Cirrhosis

Activation of neurohumoral systems (renin, AVP,

angiotensin, aldosterone)

Effective arterial blood volume

Ascites

Sinusoidal pressure(HVPG ³ 10-12 mmHg)

Sodium and water retention

Arteriolar resistance(vasodilation)

Nitric oxide synthesis by vascular endothelial

cells is increased in cirrhosis

PathogenesisofAscites

Liver

Ascites

UltrasoundistheMostSensitiveMethodtoDetectAscites

• Indications• New-onsetascites• Admissiontohospital• Symptoms/signsofSBP• Renaldysfunction• Unexplainedencephalopathy

• Contraindications• None:CanbedoneatanyINRorplateletcount

DiagnosticParacentesis

ManagementofUncomplicatedAscites

DiureticTherapy• Dosage(initialratio5:2)

• Spironolactone100-400mg/day• Furosemide(40-160mg/d)forinadequateweightlossorifhyperkalemiadevelops

• Increasediureticsifweightloss<1kginthefirstweekand<2kg/weekthereafter

• Decreasediureticsifweightloss>0.5kg/dayinpatientswithoutedemaand>1kg/dayinthosewithedema

• Sideeffects• Renaldysfunction,hyponatremia,hyperkalemia,encephalopathy,gynecomastia

RefractoryAscites

• Diuretic-intractableascites• Therapeuticdosesofdiureticscannotbeachievedbecauseofdiuretic-inducedcomplications

• Diuretic-resistantascites• Noresponsetomaximaldiuretictherapy(400mgspironolactone+160mgfurosemide/day)

• ProphylacticTIPS• 6trialsof390patients• Concludedsurvivalbenefitbasedonurinesodium,bili,andportalpressurereduction(OR0.45;95%CI,0.24-0.81)

ChenRP,etal.JClin Gastroenterol2014;48(3):290-9

Ascites

• Ascitesisthemostcommonofthe3majorcomplicationsofcirrhosis

• Occurswhenportalhypertensionhasdeveloped• 50-60%ofpatientswith“compensated”cirrhosis,i.e.,without

havingdevelopedoneofthesecomplications,developascitesduring10yearsofobservation

• 50%mortalityratewithin3years• Patientsshouldgenerallybeconsideredforlivertransplantation

referralArroyoV,Colmenero J.JHepatol.2003;38:S69-S89;EuropeanAssociationfortheStudyoftheLiver.JHepatol.2010;53:397-417.

EsophagealVarices

• Gastroesophageal varicespresentin~50%ofpatientswithcirrhosis– Presencecorrelateswithseverityofliverdisease– 40%ofChildApatientshavevarices– 85%ofChildCpatientshavevarices

• Cirrhoticpatientswithoutvaricesdevelopthematarateof8%peryear• Patientswithsmallvaricesdeveloplargevaricesatarateof8%peryear

Garcia-Tsao G,etal.Hepatology. 2007;46:922-938.

EsophagealVariceal Hemorrhage

• Occursatayearlyrateof5%to15%• Mostimportantpredictorofhemorrhageissizeofvarices• Otherpredictorsofhemorrhageare:– Decompensatedcirrhosis(ChildB/C)– Endoscopicpresenceofredwalemarks

• Associatedwithamortalityof≥20%at6weeks• Bleedingceasesspontaneouslyin≤40%ofpatients

Garcia-Tsao G,etal.Hepatology. 2007;46:922-938.

Portalpressure

Resistancetoportalflow

Cirrhosis

Splanchnicresistance

Duetonitricoxide

Portalbloodinflow

Varices VaricealGrowth

Varicespresentin40-60%ofcirrhoticpatients

VaricesandVaricealHemorrhage

Small varicesLower risk of bleeding

Large varicesHigher risk of bleeding

No varices

7-8%/year 7-8%/year

Varices IncreaseinDiameterProgressively

Merlietal.JHepatol2003;38:266

BleedingEsophagealVarices

• Riskfactors:• Largevarices• ChildsscoreC• Cherryred/redwalemarkings(endoscopicredsigns)

• HVPG>12mmHG

• 20%mortalitywithinitialbleed

BleedingGastricVarix

• 10%ofvaricealhemorrhages

• DonotrespondwelltoEBL

• Ruleoutsplenicveinthrombus

• Bleedingcontrolledin90%• Antibioticsarestandardofcare• Rebleeding rate30%• Comparedwithsclerotherapy:

• Lessrebleeding• Lowermortality• Fewercomplications• Fewertreatmentsessions

Ligated Esophageal Varix

EndoscopicVaricealBandLigation:CurrentGoldStandardforBleedingVarices

Pretreatmentcyanoacrylate Post-treatmentcyanoacrylate

GastricVarices

ManagementofAcuteGastric(Fundal)VaricealBleeding

TIPS*

VaricealHemorrhageSuspected

InitialManagement

NO

Bleedingcontrolled?

Varicealobturationpossible?

Varicealobliteration+betablockers

YES

YES

Notpossibleorrebleed

NO

• Transfusetohemoglobin~8g/dL• Earlypharmacotherapy• Antibioticprophylaxis

*SurgicalshuntmaybeconsideredforChild’sClassA

ComparativeOutcomeProbabilitiesforVariousComplicationsofCirrhosis

Complication Survivalat1Year

Survivalat3Years

Varices(Non-Bleeding)w/oAscites1 97% NA

Ascites± Varices1,2 80% 50%

BleedingVarices± Ascites1 43% NA

HepaticEncephalopathy3 42% 23%

NA=NotAvailable.1.AdaptedfromDʼAmico G,etal.JHepatol. 2006;44:217-231;2.ArroyoV,Colmenero J.JHepatol. 2003;38:S69-S89;3.AdaptedfromBustamante,etal.JHepatol.1999;30:890-895.

Summary

• CirrhosisandthedevelopmentofportalhypertensioncanresultindecompensationasmanifestbyHE,ascitesandvaricealbleeding.

• Patientswithdecompensatedliverdiseaseshouldbetreatedwiththegoaltoreduceportalpressuresandmanagethecomplicationstoimprovepatientcomfortandreducerisk.

• Decompensation isasignalformarkedincreaseriskofmorbidityandmortalityandappropriatepatientsshouldbereferredforconsiderationoflivertransplantation