Diagnosing and Managing Portal Hypertension, Ascites and Variceal Hemorrhage Fred Poordad, MD
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