Diagnosing and Managing Hepatic Encephalopathy€¦ · Diagnosing and Managing Hepatic Encephalopathy Christy Rosas, MPAS, PA-C Texas Liver Institute •60 year old male with history

DiagnosingandManagingHepaticEncephalopathy

ChristyRosas,MPAS,PA-CTexasLiverInstitute

• 60yearoldmalewithhistoryofcirrhosissecondarytoalcoholuse

• Presentedwithalcoholichepatitis,jaundiceandascites18monthsago.

• Alcoholabstinencesincethen.• Fluidoverloadresolvedwithdiuretics(spironolactone100mgdailyandfurosemide40mgdaily)

PatientDC

PatientDC

• Patientwaswelluntil1dayspriortopresentationwhenhedevelopedlethargyandslurredspeech.

• Symptomsworseneduntilhebecamedisorientedandhisfamilybroughthimforevaluation

• Nofevers,GIbleeding,edema,increasedabd girthoralcoholrecidivism

• Examinationrevealedawellappearingmaleorientedtonameonlywithnoevidenceofheadtrauma

• +asterixis

• Labsrevealaplateletcountof68K.OtherwisetheCBCandliverpanel(includingbilirubin)wereWNL.INR1.1.ElectrolytesrevealaserumNa129andaCrof1.8(baseline0.9)

• Whatdoyoususpect?

PatientDC

• PatientwashospitalizedandhydratedwithIValbuminandadministeredlactulose2tbsp tid

• Diureticswerediscontinued• Mentationandelectrolytesrapidlynormalized• Rifaximin 550mgbidwasadded.• Diureticswerenotrestarted.Thepatientwasdischargedonlactuloseandrifaximin.

PatientDC

• Questions• WhatarecommonprecipitatingfactorsofacuteovertHE?

• IsserumNH3levelanimportantdiagnosticstrategyinapatientwiththispresentation?

• HowdoyoutreatacuteovertHE?• WhatisanappropriatestrategytopreventrecurrenceofHE?

PatientDC

Yourliverisanamazingfactorywhichisinvolvedinmanytasksyourbodyneeds:• Helpsindigestionthroughtheproductionofbile.• Providesstorageforessentialnutrientssuchasiron,vitaminsand

minerals.• Storesenergybystockpilingcarbohydrates,glucoseandfats.• Metabolizeswhatyouingestsuchasdrugsandmedications.• Detoxifiesingestedsubstancessuchasalcohol,chemicals.• Makesproteinsthatyouneedtostayhealthyandgrow.• Makesclottingfactorsthatstopbleeding.

YourLiver:WhatDoesItDoForYou?

• Theliverrespondstoinjurybyreplacingdamagedtissuewithscartissue

• Whatiscirrhosis?• Permanentscarringoftheliver;hardscartissuereplacessofthealthytissue

• Cirrhosisdoesnotidentifyeitherthecauseofthedamageortellusaboutthefunctionoftheliver

• Peoplemayhavecirrhosis,stillappearhealthyandnotknowtheyhaveliverdamage

WhatHappenstotheLiverWhenIt’sInjured?

StagesofChronicLiverDisease

Ramos-Lopezetal.,WorldJGastroenterol.Nov7,2015;21(41):11552-11566

CausesofChronicLiverDisease

• HCVandNASHarethemostcommoncausesofcirrhosisintheUS1

• HCVandNASHaregrowinginprevalencethereforecirrhosisratesareincreasing2,3

HCV

26%

NASH

21% HCVplusNASH15%

Cryptogeniccauses(ManycasesactuallyareduetoNAFLD)18%

HBV

15%

Miscellaneous5%

CausesofCirrhosisintheUS2

HBV=HepatitisB;HCV=HepatitisC;NASH=Nonalcoholicsteatohepatitis;NAFLD=NonalcoholicFattyLiverDisease1.Wolf.DCAvailableat:http://emedicine.medscape.com/artciel/185856-overview#aw2aa6b3.2.WilliamsCD,etal.Gastroenterology. 2011;140:124–131.3ArmstrongGL,etal.AnnInternMed.2006;144:705–14.

403,665 411,029436,901 444,883 459,496

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USHospitalDischargesDuetoCirrhosisAreIncreasing

*ICD-9-CMdiagnosiscodes571.2.571.5,571.6;alllisteddiagnoses.HCUPnet,HealthcareCostandUtilizationProject.AgencyforHealthcareResearchandQuality,Rockville,MD.http://hcupnet.ahrq.gov.

Cirrhosis:SymptomsandSigns• Anorexia,weightloss• Weakness,fatigue• Muscleloss,cramps• Nausea• Vague(RUQ)abdominalpain• Pruritus• Easybruising,epistaxis• GIbleeding• Confusion,sleepdisturbance• Amenorrheaorirregularmenses

• Spiderangiomata• Palmarerythema• Gynecomastia,testicularatrophy• Abdominaldistention,edema• Parotidhypertrophy• Dupuytren’s contractures• Clubbing,leukonychia• Jaundice,icterus• Splenomegaly• Asterixis,fetorhepaticus• Cachexia

Liverinsufficiency

Varicealhemorrhage

Cirrhosis Ascites,Hydrothorax

Portalhypertension

SBP

Hepatorenalsyndrome

“Coagulopathy”JaundiceHypoalbuminemia

Portopulmonary hypertensionHepatopulmonary syndrome

FocusWillBeHepaticEncephalopathy

Encephalopathy

• Reversiblesyndromeofimpairedbrainfunctionseeninpatientswithadvancedliverdisease

• Mechanism:• Damagedlivercan’tremovetoxinsfromblood,e.g.,ammonia

• Reducednumberoflivercellstodothejoboftoxinremoval• Shuntingofbloodfromthegutaroundthedamagedliverallowstoxinstoenterthebloodstream

• ToxinsbuildupandgetintobraincausingtemporaryworseningofbrainfunctionresultinginHE

WhatisHepaticEncephalopathy(HE)?

WhatCanTriggerHE?• Non-compliance• Infections• Constipation• Dehydration• Bleedingfromstomach,intestines,oresophagus

• Medicationsthataffectyournervoussystem:

• Sleepingpills• Antidepressants• Painmedications

• Kidneyproblems• Analcoholbinge• Surgery• Havingaportosystemicshunt:

• Tubeplacedinyourliver(TIPS)• Surgicalproceduretoreroutebloodflowandrelievehighbloodpressureinveinsin/aroundliver(portalHTN)

• GItractisprimarysource• Producedbycellsinsmallintestineandbacteriaincolon

• Entersthecirculationviatheportalvein• Theportalveintakesallthebloodcomingfromthegutandroutesittotheliverbeforeitgoesouttotherestofthebody

• Intactlivercellsclearalmostallammoniaandothertoxins

WhereDoAmmoniaandOtherToxinsComeFrom?

http://www.webmd.com/digestive-disorders/digestive-diseases-portal#1

• Thereisnospecific“HEtest.”• Diagnosisisbasedonacombinationofthreethings:

• Patientsymptoms• Patientmedicalhistory

• Caregiversatmedicalvisithelpful• Athoroughclinicalexam

• AlternativecausesofAMSshouldbesoughtandtreated (e.g.DKA,drugs,neuroinfections,electrolytedisorders,intracranialbleedingandstroke

HowisHEDiagnosed?

MentalSymptomsofHEMildtomoderatesymptoms

• Shortattentionspan• Mildconfusion• Forgetfulness• Moodswings• Personalitychanges• Inappropriatebehavior• Difficultydoingbasicmath

Moreseveresymptoms

• Markedconfusion• Severeanxietyorfearfulness• Disorientationregardingtime/place

• Coma

PhysicalSymptomsofHE

Mildtomoderatesymptoms

• Changeinsleeppatterns• Difficultywritingordoingsmallhandmovements

• Breaththatsmellsmustyorsweet• Slurredspeech

Moreseveresymptoms

• Extremesleepiness• Slowedorsluggishmovement• Shakingofhandsorarms(called“flapping”orasterixis)

• Jumbledspeechthatcan’tbeunderstood

• Coma

Normal “Covert” HE I II III IV

“Overt” HE Stages

Categorizationisoftenarbitraryandvariesbetweenraters

ClinicalDiagnosis

Worsening cognitive dysfunction

coma

CharacterizationofHEStages

BajajJS,etal.Hepatology.2009;50:2014-2021.

• Patientswithconfusionandpoorfunctionareatincreasedriskoffallsandinfections.

• PatientswithHErequiremorehospitalizationsandareatincreasedriskfordeath.

• Caregiversofpatientswithconfusionhaveagreaterburdenresultinginincreasedstressandlossofwork.

• Treatmenthasbeenshowntodecreasebothcaregiverburdenandhospitalizationsinpatients.

WhyIt’sImportanttoTreatHE

Treatmentvariesdependinguponanumberoffactorsincludingtheprecipitatingcause,ortriggeringeventaswelltheseverityofsymptoms.

Therapiesmayinclude:• Medicationstotreatinfection• Hydration• Proceduretocontrolbleeding• Stoppingmedicationsthattriggeredepisode

TreatmentOverview

FDAApprovedTreatmentOptionsforHEDrugName MechanismofAction1 PotentialAdverseEffects

Lactulose15-30mlPOBID/TIDTitrateto2-3soft

BMs/day

•Decreasesbloodammoniaconcentration- PromoteseliminationofNH3- Fermentationbybacteriaacidifycolonandpreventabsorption

- Reducesurease-producingbacteria

Overusecanleadtoaspiration,dehydration,hypernatremia,andsevereperianalskinirritation;overusecanevenprecipitateHE2

Rifaximin550mgPOBID

•Decreasesbloodammoniaconcentration- Broadspectrumantibiotic;resultsinachangeinbowelflora

- Maycausedownregulation ofintestinalglutaminase activity

Diarrhea(duetoovergrowthofCdiff)peripheraledema,nausea,dizziness,fatigue,andascites3

Neomycin•Decreasesbloodammoniaconcentration- Inhibitsintestinalglutaminase.Uselimited.

•Shouldnotbeusedinclinicalpractice

RiskofCdiffRiskofototoxicityandnephrotoxicitywithlong-termtreatmentduetosomesystemicabsorption

1.AdaptedfromKhungar V,Poordad F.Clin LiverDis.2012;16:301–320.2.Vilstrup H,etal.Hepatology. 2014;60:715-35.3.Xifaxan PI.2015;SalixPharmaceuticals,Bridgewater,NJ.

• Goaloftreatmentistominimizesymptoms,improveoverallqualityoflifeandpreventhospitalizations.

• LactuloseisrecommendedforpreventionofrecurrentepisodesofHEaftertheinitialepisode

• Rifaximin asanadd-ontolactuloseisrecommendedforpreventionofrecurrentepisodesofHEafterthesecondepisode

• Routineprophylactictherapy(lactuloseorrifaximin)isnotrecommendedforthepreventionofpost-TIPSHE

• Undercircumstanceswheretheprecipitatingfactorshavebeenwellcontrolled(i.e.,infectionsandVB)orliverfunctionornutritionalstatusimproved,prophylactictherapymaybediscontinued

PreventionofOvertHE(OHE)

AASLDPracticeGuideline,2014

• Hepaticencephalopathyisakeysignofend-stageliverdisease.

• HEisreadilytreatableandactiveinterventionscandecreasehospitaladmissionrates.

• Rifaximin,combinedwithlactulose,isacommoncareoptionforHEmanagementinthecommunity.

• Familiarizeyourselfwithguidelinesforitsdiagnosis,classification,andtreatment.

Conclusion