Andersons pediatric cardiology 1916

report,almostallpatientshadsomeevidenceofliverabnormality20years
followingtheFontanprocedure,withathirdhavingregenerativenodulesand
6%establishedcirrhosis.Asreportedelsewhere,therewaslittlecorrelation
betweenliverabnormalitiesandclinicalstatus.166Otherfactorsmayalso
contributetoliverdiseaseintheFontanpopulation,includinghypoxemic
damageoccurringduringepisodesoflowcardiacoutput.HepatitisCinfection
shouldbeconsideredinolderpatientswhohadcardiacsurgerypriortoscreening
forthevirus,asshouldalcohol-relatedliverdamage.
TheclinicalcharacteristicsofFontan-associatedliverdiseaseremaintobe
clearlydefined,but,asmorepatientssurviveintoadulthood,itisbecoming
apparentthatthediseaseissimilartootherformsofliverdiseasewithvariable
degreesoffibrosisandcirrhosis.Mildabnormalitiesofliverenzymes,especially
γ-glutamyltransferase,arecommon,asisaminorelevationintheindirect
bilirubin.Exceptingforamildelevationintheprothrombintime,indicesof
syntheticfunctionsuchasalbuminareusuallynormalunlessthereisadvanced
cirrhosis(orPLE).167
Ultrasoundoftheliverfrequentlydemonstratesheterogeneousechotexture
andarterializednodules.168Thesenodulesarestrikingbutappeartobebenign
andmaybeanattempttoincreasebloodflowtotheliverbyincreasingarterial
supply.161MRIorultrasoundelastographyoftheliverdemonstratesincreased
liverstiffness.169–174Althoughthisfindingislikelyacombinedresultof
congestionandfibrosis,onesmallstudyhasshownthatliverandsplenic
stiffnessonelastographywasstronglycorrelatedwiththedegreeofbiopsyprovenfibrosis.172
PerhapsthemostfearedconsequenceofadvancedliverdiseaseintheFontan
circulationisthedevelopmentofhepatocellularcarcinoma.175–179Whatonce
seemedisolatedtorarecasereportshasbecomemorecommonasmorepatients
survivewellintoadulthood.Unfortunately,thedetectionofhepatocellular
carcinomamaybechallenging,particularlyonabackgroundofabnormal
hepaticparenchyma.180Screeningtestssuchasserumα-fetoproteinmaybe
helpfulbutarenotsensitiveorspecificenoughtoreliablydiagnoseeachcase.
Regularabdominalultrasoundtodetectnodulargrowthmaybehelpful.Contrast

computedtomography(CT)orMRI,boththegoldstandardfordiagnosisof
hepatocellularcarcinomainothersettings,maybelessreliableintheFontan
circulation.Thetumorissuppliedfromthehepaticarterialcirculation,whereas
thenormalliverreceivesmostofitsbloodsupplyfromtheportalvein.These


testsdetectearlycontrastenhancementinthetumorandlaterenhancementinthe
surroundingtissue.ElevatedsystemicvenouspressureintheFontancirculation
mayinterferewiththisrelationship.181
Inadditiontothedevelopmentofhepatocellularcarcinoma,progressionof
cirrhosisanditscomplicationsmayheraldthefailureoftheFontancirculation.
Portalhypertensionisnotuncommon,withsplenomegalyseenin20%of
patientsatamedianof10yearsaftertheFontanoperation.Venouscollaterals
fromtheliveroresophagealvaricesareseeninmorethanhalfofthosewith
functionallimitation.182Abdominalascitesmaybecardiacinoriginbutcanalso
beassociatedwithlivercirrhosis.Inthissetting,thedevelopmentofascitesisa
poorprognosticsign.Asintraabdominalfluidincreases,aviciouscycleensues
withincreasedabdominalpressureleadingtoincreasedvenoushypertensionand
anevenmorepronounceddecreaseincardiacoutput.Ascitesisoftenrelatively
resistanttodiuretictreatmentand,whilenotreportedintheliterature,some
patientshavebeenmanagedwithrepeatedperitonealtapstodrainabdominal
fluidinthehopeofmaintainingafunctionalFontancirculationeitherasa
palliativeprocedureorwhileawaitingheartorheartandlivertransplantation.
Liverdiseaseisafrequent,seriousandprogressiveentityfollowingthe
Fontanoperation,butscreeningalgorithmsandmanagementarelesswell
defined.Serialmonitoringwithliverbiopsyisnotpracticalandmaybeimpacted
bytheheterogeneityofthehepaticmanifestations.Fornow,regularsurveillance
withabdominalultrasoundandelastography,aswellasserialmeasurementsof
serumα-fetoprotein,maybethebestoption,particularlyinthosepatientsmore
than10yearsoutfromtheFontanprocedure.Multiplesocieties,interestgroups,

andindividualsareworkingonfollow-upprotocolsforallorgansystems,
particularlytheliver.183,184Continuedworktowardthedevelopmentofmedical
andsurgicalstrategiestolowervenouspressureandimprovecardiacoutputmay
slowtheprogressionofliverdisease.TheFontanoperationhashelpedtosaveor
prolongmanylives,butmoreworkisneededtohelpmanagethecomplications
thatresultfromthisuniquecirculation.

LymphaticInsufficiency
ThephysiologycreatedbytheFontanoperationresultsinbothobligatecentral
venoushypertensionandpersistentlowcardiacoutput.185Althoughthese
physiologicabnormalitiesmaybewelltolerated,atleastforafewdecades,there
isasubsetofpatientsinwhomseverecomplicationsmayoccurmuchearlier.


PlasticbronchitisandPLEarebothfearedcomplicationsoftheFontan
circulation,andbothmayleadtosignificantmorbidityandmortality.155,186
Inrecentyears,agreatdealhasbeenlearnedabouttheroleofthelymphatic
systeminthepathophysiologyofplasticbronchitisandPLE.187–189The
lymphaticsystem,thescavengerofthecirculatorysystem,isresponsiblefor
retrievinginterstitialfluidandreturningittothecentralcirculationviathe
connectionofthethoracicducttotheinnominatevein.ForpatientswithFontan
physiology,thereisobligatelymphatichypertensionthatresultsfromthe
transmissionoftheelevationinCVP(Fig.73.20).Thelymphaticsystemis
furtherinundatedbytheincreaseinlymphaticfluidproductionthatresultsfrom
increasedintravascularandintrahepatichydrostaticpressureassociatedwith
heartfailure.190AlthoughMRIimagingdemonstratesuniversaldilationofthe
lymphaticsinpatientswithFontanphysiology,thereappeartobesomepatients
inwhomthelymphatichypertensionanddilationleadtolymphaticinsufficiency,
oftenwithsevereconsequences.

FIG.73.20 Elevatedcentralvenouspressureresultsinincreased
lymphaticproductionandelevatedintralymphaticpressureleadingto
lymphaticinsufficiency.

PlasticBronchitis
Plasticbronchitisischaracterizedbythedevelopmentofabnormallymphatic
vesselsintheperibronchialregion.Theseabnormalvesselsformtinyfistulous
connectionstotheairways,allowingforaslowbutinsidiousleakageof
lymphaticfluid.Thefluiditselfdissipatesovertimewithrespiration,leaving