Portal Hypertensive Gastropathy - egfrhep.comPortal Hypertensive Gastropathy Prevalence (Prevalence (22))::--Definite correlation between portal pressure and Definite correlation between

Portal Hypertensive Portal Hypertensive GastropathyGastropathy

HishamHisham R. R. ElKhayatElKhayat, M.D , FACG,FASGE,MAGA, M.D , FACG,FASGE,MAGA

PROF. OF GI & HEPATOLOGYPROF. OF GI & HEPATOLOGY

THEODOR BILHARZ RESEARCH INSTITUTETHEODOR BILHARZ RESEARCH INSTITUTE

Portal HypertensivePortal HypertensiveGastropathyGastropathy

--Definition.Definition.

--Classification.Classification.

--Prevalence.Prevalence.--Prevalence.Prevalence.

--Pathogenesis.Pathogenesis.

--GAVE.GAVE.

--Natural history & Complication.Natural history & Complication.

--Management.Management.

Portal HypertensivePortal Hypertensive

GastropathyGastropathy

-- Definition.Definition.

-- Classification.Classification.

-- Prevalence.Prevalence.-- Prevalence.Prevalence.

-- Pathogenesis.Pathogenesis.

-- GAVE.GAVE.

-- Natural history & Complication.Natural history & Complication.

-- Management.Management.




--Definition :Definition :ItIt isis thethe termterm usedused toto describedescribe thethe endoscopicendoscopic

appearanceappearance ofof gastricgastric mucosa,mucosa, withwith thethe ChCh..ChCh..mosaicmosaic--likelike patternpattern withwith oror withoutwithout redred spotsspots ,, seenseen inin patientspatientslikelike patternpattern withwith oror withoutwithout redred spotsspots ,, seenseen inin patientspatientswithwith cirrhoticcirrhotic oror nonnon--cirrhoticcirrhotic portalportal hypertensionhypertension..

TypicallyTypically thethe whitewhite reticularreticular networknetwork separatingseparating areasareasofof raisedraised redred oror pinkpink mucosamucosa resemblingresembling thethe skinskin ofof aasnakesnake..

TheseThese changeschanges areare notnot uniqueunique toto gastricgastric mucosamucosa asassimilarsimilar changeschanges areare maymay alsoalso seenseen inin smallsmall intestineintestineandand coloncolon.. ThuluvathThuluvath andand YooYoo ,, 20022002


�� Definition.Definition.

�� Classification.Classification.

�� Prevalence.Prevalence.�� Prevalence.Prevalence.

�� Pathogenesis.Pathogenesis.

�� GAVE.GAVE.

�� Natural history & Complication.Natural history & Complication.

�� Management.Management.

Portal Hypertensive Portal Hypertensive GastropathyGastropathy Scoring Scoring

System as Proposed at the System as Proposed at the BavenoBaveno Consensus Conference (Sarin,Consensus Conference (Sarin,19961996))

ScoreScoreParameterParameter

11

22

11--Mucosal MP.Mucosal MP.

MildMild

SevereSevere 22 SevereSevere

11

22

22--Red markings.Red markings.

IsolatedIsolated

ConfluentConfluent

00

22

33--GAVE.GAVE.

AbsentAbsent

PresentPresent

Mild gastropathy =score≤Mild gastropathy =score≤33

Severe gastropathy = score≥Severe gastropathy = score≥44

Validation Validation 00f Baveno scoring f Baveno scoring systemsystem

�� NotNot onlyonly BavenoBaveno scoringscoring systemsystem ofofPHGPHG isis reproduciblereproducible andand validvalid butbut ititaccuratelyaccurately reflectsreflects thethe risksrisks ofof PHGPHG..accuratelyaccurately reflectsreflects thethe risksrisks ofof PHGPHG..

�� AsAs thethe riskrisk ofof recurrentrecurrent bleedingbleeding waswasrelatedrelated toto severesevere PHGPHG scoresscores (>(>44))togethertogether withwith thethe presencepresence ofof severesevereredred markingsmarkings ,, GAVEGAVE andand nodularnodularlesionlesion inin thethe antrumantrum..

StewartStewart andand SanyalSanyal ,, GIGI ,, 20032003

Nodular Lesion Associated With Nodular Lesion Associated With PHGPHG

StewartStewart andand SanyalSanyal ,, GIGI ,, 20032003

Nodular lesion associated Nodular lesion associated with PHGwith PHG

�� It reflects not only severe PHG but It reflects not only severe PHG but also the risk of PHG related bleeding. also the risk of PHG related bleeding.

�� Histology shows , mucosal hyperplasia Histology shows , mucosal hyperplasia �� Histology shows , mucosal hyperplasia Histology shows , mucosal hyperplasia , dilated capillaries in the lamina , dilated capillaries in the lamina propria , and hypertrophy of the propria , and hypertrophy of the muscularis mucosa.muscularis mucosa.

Stewart and Sayal, GI , Stewart and Sayal, GI , 20032003







�� GAVE.GAVE.




Prevalence (Prevalence (11):):-- The overall prevalence of PHG ranges from The overall prevalence of PHG ranges from

5151--9898%. %. 5151--9898%. %. -- ThisThis widewide variationvariation inin differentdifferent studiesstudies isis

duedue toto patientpatient selectionselection ,, absenceabsence ofofuniformuniform classificationclassification andand moremoreimportantlyimportantly ,, thethe differencedifference inin interinter--andandintraintra--observerobserver variationvariation..

Thuluvath and yoo , Thuluvath and yoo , 20022002


Prevalence (Prevalence (22):):-- Definite correlation between portal pressure and the Definite correlation between portal pressure and the

presence or severity of PHG. presence or severity of PHG. IwaoIwao et al., et al., 19971997

-- NoNo linearlinear relationshiprelationship withwith thethe severityseverity ofof liverliver diseasedisease..-- NoNo linearlinear relationshiprelationship withwith thethe severityseverity ofof liverliver diseasedisease..NICENICE ,, 20002000

--TheThe prevalenceprevalence ofof PHGPHG doesdoes increaseincrease withwith varicealvaricealobliterationobliteration..

TanoueTanoue etet alal..,,19921992ThuluvathThuluvath andand yooyoo ,, 20022002ELEL KHAYATKHAYAT etet alal..,, 20052005







�� GAVE.GAVE.





Pathogenesis(Pathogenesis(11):):-- PortalPortal hypertensionhypertension isis thethe keykey factorfactor forfor PHGPHG

developmentdevelopment whereaswhereas GAVEGAVE dependsdepends onon thetheseverityseverity ofof liverliver diseasedisease ..severityseverity ofof liverliver diseasedisease ..

BayraktarBayraktar etet alal..,, 19961996

MasukoMasuko etet alal..,, 19991999

-- MoreoverMoreover TIPSTIPS andand shuntshunt surgerysurgery improveimprove PHGPHGbutbut notnot GAVEGAVE..

IwaoIwao etet alal..,,19971997



Pathogenesis (Pathogenesis (22):):--IncreaseIncrease gastricgastric mucosalmucosal bloodblood flowflow ,gastric,gastric mucosalmucosal

defensedefense impairmentimpairment andand activationactivation ofof cytokinescytokines andandgrowthgrowth factorfactor likelike nitricnitric oxideoxide andand enothelinenothelin--11 ,, VEGFVEGFcontributecontribute toto thethe developmentdevelopment ofof PHGPHG..contributecontribute toto thethe developmentdevelopment ofof PHGPHG..

ThuluvathThuluvath andand yooyoo ,, 20022002

--OxidativeOxidative stressstress inducedinduced mitogenmitogen--activatedactivated proteinprotein kinasekinasephosphatasephosphatase 11 waswas foundfound toto bebe overover--expressedexpressed inin PHGPHGwhichwhich waswas normalizednormalized afterafter supplementationsupplementation withwith vitvit..EE..

KawanakaKawanaka etet alal..,, 20012001






�� GAVE.GAVE.



GAVEGAVE

GAVEGAVE� GAVE is a term used for the typical endoscopicfindings of red strips , separated by normalmucosa commonly seen in the gastric antrum.

Jabbari et al., 1984Jabbari et al., 1984

� Reported in a variety of autoimmune diseases ,connective tissue diseases , hypothyroidism ,pernicious anaemia and PBC.

Gostout et al., 1992

GAVEGAVE�� HistologicallyHistologically ,, GAVEGAVE isis differentdifferent fromfrom PHGPHG asas therethereisis markedmarked capillariescapillaries ,, collectingcollecting venulesvenules dilatationdilatationinin thethe mucosamucosa && submucosasubmucosa plusplus fibrohyalinosisfibrohyalinosis ,,fibrinfibrin thrombithrombi asas wellwell asas spindlespindle cellcell proliferationproliferation..fibrinfibrin thrombithrombi asas wellwell asas spindlespindle cellcell proliferationproliferation..

�� GAVEGAVE isis aa distinctdistinct clinicalclinical andand pathologicalpathological entityentityandand itsits pathogenesispathogenesis isis poorlypoorly understoodunderstood.. PossiblePossiblemechanismsmechanisms includeinclude humoralhumoral factorsfactors suchsuch asasgastringastrin ,, prostaglandinprostaglandin ,, serotoninserotonin ,, VIPVIP andandcellularcellular growthgrowth factorsfactors..

PayenPayen etet alal..,, 19951995






�� GAVE.GAVE.



Natural History&ComplicationsNatural History&Complications

--AcuteAcute bleedingbleeding fromfrom PHGPHG isis lowlow andandisis seenseen mostlymostly inin moremore severesevere PHGPHG..

SarinSarin etet alal..,, 20002000SarinSarin etet alal..,, 20002000

--TheThe mortalitymortality associatedassociated withwithbleedingbleeding fromfrom PHGPHG isis veryvery lowlowbecausebecause mostmost bleedsbleeds areare minorminorcomparedcompared toto varicealvariceal bleedingbleeding..

ThuluvathThuluvath andand yooyoo..,, 20022002

Natural History&Complications(Natural History&Complications(22))

-- EndoscopicEndoscopic sclerotherapysclerotherapy andand bandingbanding worsenworsenthethe severityseverity ofof PHGPHG andand increasesincreases thethe riskrisk ofofbleedingbleeding duedue toto alterationalteration ofof locallocalhaemodynamicshaemodynamics afterafter obliterationobliteration ofof OO..VV.. AlsoAlsodelayeddelayed gastricgastric emptyingemptying ,, fromfrom thethe chemicalchemicalhaemodynamicshaemodynamics afterafter obliterationobliteration ofof OO..VV.. AlsoAlsodelayeddelayed gastricgastric emptyingemptying ,, fromfrom thethe chemicalchemicalvagotomyvagotomy afterafter sclerotherapysclerotherapy ,, hashas beenbeenallegedalleged asas aa possiblepossible mechanismmechanism forfordevelopmentdevelopment ofof PHGPHG..

BalanBalan et al., et al., 19991999

SarinSarin et al., et al., 20002000

Lo et al., Lo et al., 20012001

El El KhayatKhayat et al., DDW , et al., DDW , 20102010






�� GAVE.GAVE.



Management Management

-- AS AS prophylaxisprophylaxis of PHG bleeding :Non selective of PHG bleeding :Non selective ββ

blocker , reduces portal pressure and gastric mucosal blood flow.blocker , reduces portal pressure and gastric mucosal blood flow.

Hosking et al., Hosking et al., 1987 1987 Hosking et al., Hosking et al., 1987 1987

PerezPerez--ayusoayuso et al., et al., 19911991

-- However bleeding from GAVE unlike PHG is not known to respond However bleeding from GAVE unlike PHG is not known to respond to to nonselectivenonselective ββ--blocker.blocker.

-- Vitamin E normalize Vitamin E normalize mitogenmitogen--activated protein activated protein kinasekinase phosphatasephosphatase11, thus improves PHG. , thus improves PHG.

KawanakaKawanaka et al., et al., 20012001


-- MulicenterMulicenter studystudy inin upperupper EGYPTEGYPT ,,carvidilolcarvidilol 66..2525 mgmg bidbid plusplus vitaminvitamin EE 10001000improvedimproved PHGPHG ,, decreaseddecreased thethe likelyhoodlikelyhoodofof chronicchronic bleedingbleeding andand increasedincreased thetheimprovedimproved PHGPHG ,, decreaseddecreased thethe likelyhoodlikelyhoodofof chronicchronic bleedingbleeding andand increasedincreased thetheHCTHCT significantlysignificantly inin cirrhoticcirrhotic EGYPTIANEGYPTIANsufferingsuffering fromfrom anaemiaanaemia duedue PHGPHG withwith nonoevidenceevidence ofof otherother causescauses ofof bleedingbleeding..

EL KHAYAT et al., IN PRESS , EL KHAYAT et al., IN PRESS , 20112011


-- Of acute bleeding of PHG ::•• SomatostatinSomatostatin andand vasopressinvasopressin andand glypressinglypressin

forfor temporarytemporary managementmanagement ofof acuteacute PHGPHG

bleedingbleeding..bleedingbleeding..EscorsellEscorsell etet alal..,, 20012001

•• EndoscopicEndoscopic managementmanagement ofof acuteacute PHGPHG bleedingbleedingbyby sclerosantsclerosant ,, heaterheater probeprobe ,, laserlaser oror APCAPC isispossiblepossible..

•• TipsTips oror shuntshunt surgerysurgery areare thethe lastlast resortresort ..ThuluvathThuluvath andand YooYoo ,, 20022002

�� InIn studystudy thatthat waswas conductedconducted recentlyrecently inin TBRITBRI inin 3030cirrhoticcirrhotic patientspatients withwith bleedingbleeding fromfrom PHGPHG ..

�� APCAPC applicationapplication improvedimproved significantlysignificantly severityseverity ofof PHGPHGasas wellwell asas GAVEGAVE bothboth endoscopicallyendoscopically andand histologicallyhistologically..

APC for PHG and GAVE APC for PHG and GAVE

�� AlsoAlso APCAPC capablecapable ofof achieveachieve goodgood haemostatichaemostatic goalgoalwithwith improvementimprovement ofof patientspatients HCTHCT andand reductionreduction ofofthethe needneed ofof bloodblood transfusiontransfusion..

�� NotNot onlyonly thatthat butbut tissuetissue expressionexpression ofof VEGFVEGF asas wellwell asasthethe extentextent ofof angiogenesisangiogenesis andand vascularvascular ectasiaectasia wereweresignificantlysignificantly amelioratedameliorated afterafter APCAPC..

ABOULELEZZABOULELEZZ etet alal..,, 20052005

Vascular Vascular ectasiaectasia in gastric in gastric antrumantrum of a case of severe PHG of a case of severe PHG before application of APC. The mucosal glands showed before application of APC. The mucosal glands showed focal focal cryptitiscryptitis and the lamina and the lamina propriapropria showed chronic showed chronic inflammatory infiltrate and mild fibrosis (MT X inflammatory infiltrate and mild fibrosis (MT X 200200).).

After application, disappearance of the vascular ectatic After application, disappearance of the vascular ectatic channels, branching of the mucosal glands and mild channels, branching of the mucosal glands and mild decrease in associated inflammation (MT X decrease in associated inflammation (MT X 200200). ).

A case of severe PHG showing intense expression of A case of severe PHG showing intense expression of VEGF.VEGF.

Significant improvement postSignificant improvement post--APC application, showing APC application, showing mild expression of VEGF mainly in stromal and vascular mild expression of VEGF mainly in stromal and vascular endothelial cells of the lamina and focally in glandular endothelial cells of the lamina and focally in glandular epithelium.epithelium.

ENDOSCOPIC MANAGEMENT ENDOSCOPIC MANAGEMENT OF GAVEOF GAVE

�� APCAPC.. HerreraHerrera etet alal..,, 20082008

�� ENDOSCOPICENDOSCOPIC BANDBAND LIGATIONLIGATION.. WELLSWELLS etet alal..,,20082008�� ENDOSCOPICENDOSCOPIC BANDBAND LIGATIONLIGATION.. WELLSWELLS etet alal..,,20082008

�� CRYOTHERAPYCRYOTHERAPY ABLATIONABLATION.. CHOCHO etet alal..,, 20082008

�� ENDOMUCOSALENDOMUCOSAL ABLATIONABLATION USINGUSING HALOHALOSYSTEMSYSTEM..

ANDREWANDREW GROSSGROSS etet alal..,, 20082008

EVL FOR GAVE EVL FOR GAVE

EVL VS ETT for TTT of GAVEEVL VS ETT for TTT of GAVE

�� InitialInitial experienceexperience suggestssuggests thatthat EVLEVL isissuperiorsuperior toto ETTETT inin managementmanagement ofof GAVEGAVEasas EVLEVL requiresrequires fewfew TTTTTT sessionsession forforcontrolcontrol ofof bleedingbleeding withwith significantsignificantasas EVLEVL requiresrequires fewfew TTTTTT sessionsession forforcontrolcontrol ofof bleedingbleeding withwith significantsignificantimprovementimprovement ofof HCTHCT asas wellwell asas reductionreductioninin thethe transfusiontransfusion requiredrequired andandhospitalizationhospitalization staystay..

WellsWells etet alal..,, GastrointestGastrointest EndoscEndosc ,,20082008

Portal hypertensive EnteropathyPortal hypertensive Enteropathy

Portal Hypertensive Enteropathy Portal Hypertensive Enteropathy (PHE)(PHE)

�� PHEPHE isis anan uncommonuncommon causecause ofofbleedingbleeding inin PHTPHT patientspatients ,,howeverhowever therethere areare somesomehoweverhowever therethere areare somesomedescriptiondescription ofof bleedingbleeding ilealilealvaricesvarices andand duedue toto PHEPHE

SantoroSantoro etet alal..,,19971997 && OhtaniOhtani etet alal..,, 19991999 && VaranasiVaranasi etet alal..,, 20002000

Portal Hypertensive Enteropathy Portal Hypertensive Enteropathy (PHE)(PHE)

�� EndoscopicEndoscopic portalportal hypertensivehypertensive jejunopathyjejunopathy waswaspresentpresent inin 1515%% ofof patientspatients withwith PHTPHT inin aa recentrecentprospectiveprospective studystudy ,, thesethese changeschanges werewere mildmild inin 8383%% ofofcasescases andand allall patientspatients hadhad PHGPHG..prospectiveprospective studystudy ,, thesethese changeschanges werewere mildmild inin 8383%% ofofcasescases andand allall patientspatients hadhad PHGPHG..

Nutan et al.,Nutan et al.,20042004

�� InIn anotheranother prospectiveprospective studystudy ,, portalportal hypertensivehypertensiveileopathyileopathy waswas encounteredencountered inin 2525%% ofof PHTPHT patientspatientswhereaswhereas ilealileal varicesvarices waswas depicteddepicted inin 1818%% ofof studiedstudiedcasescases andand ileopathyileopathy waswas significantlysignificantly moremore commoncommon ininpatientspatients withwith portalportal hypertensivehypertensive colopathycolopathy..

MisraMisra etet alal..,, 20042004

PHE INCREASE AFTER VARICEAL PHE INCREASE AFTER VARICEAL OBLITERATIONOBLITERATION

�� TheThe numbernumber ofof patientspatients withwith PHEPHEincreasedincreased fromfrom 66..55%% beforebefore varicealvaricealobliterationobliteration toto 4646..77%% afterafter obliterationobliteration..

�� AngiogenesisAngiogenesis ,, vascularvascular ectasiaectasia andand bloodblood�� AngiogenesisAngiogenesis ,, vascularvascular ectasiaectasia andand bloodbloodextravasationextravasation inin jejunaljejunal biopsiesbiopsies wereweresignificantlysignificantly increasedincreased afterafter varicealvaricealobliterationobliteration..

ElEl KhayatKhayat etet alal..,, DDWDDW ,,20102010ElEl KhayatKhayat etet alal..,, jj GastGast..liverliver disdis..,, 20102010

Portal Hypertensive EnteropathyPortal Hypertensive Enteropathy




Portal Hypertensive ColopathyPortal Hypertensive Colopathy

Portal Hypertensive Colopathy(PHC)Portal Hypertensive Colopathy(PHC)

�� PHC spectrum includes , anorectal or PHC spectrum includes , anorectal or colonic varices and mucosal changes colonic varices and mucosal changes similar to PHG ranging from: similar to PHG ranging from: similar to PHG ranging from: similar to PHG ranging from:

--Patchy hyperemia .Patchy hyperemia .--Diffuse hyperemia with oedema Diffuse hyperemia with oedema

resembling chronic colitis resembling chronic colitis --Spider angiomata.Spider angiomata.--Severe acute colitisSevere acute colitis--like appearance with like appearance with

spontaneous bleeding from the mucosa.spontaneous bleeding from the mucosa.

Portal Hypertensive ColopathyPortal Hypertensive Colopathy

Portal Hypertensive Colopathy(PHC)Portal Hypertensive Colopathy(PHC)

�� There is an inverse relationship in There is an inverse relationship in the colon between the severity of the colon between the severity of colonic varices and PHC , as it is colonic varices and PHC , as it is colonic varices and PHC , as it is colonic varices and PHC , as it is possible that anorectal varices possible that anorectal varices decompress the colonic portal decompress the colonic portal venous system and consequently venous system and consequently colopathy is found less often in colopathy is found less often in patients with anorectal varices.patients with anorectal varices.

Bini et al., Bini et al., 2000 2000 & Misra et al., & Misra et al., 20042004

Final message !Final message !

�� MP , red marks and GAVE are found with MP , red marks and GAVE are found with incremental frequency in patients with incremental frequency in patients with cirrhosis and PHT.cirrhosis and PHT.

�� MP is not unique to PHG as it occurs in small MP is not unique to PHG as it occurs in small and large intestine in PHT (PHE& PHC , and large intestine in PHT (PHE& PHC , and large intestine in PHT (PHE& PHC , and large intestine in PHT (PHE& PHC , respectively).respectively).

�� BavenoBaveno scoring is system is reproducible scoring is system is reproducible and accurately identifies the risk of and accurately identifies the risk of bleeding.bleeding.

�� APC is valuable in dealing with bleeding PHG APC is valuable in dealing with bleeding PHG & GAVE but is not optimum.& GAVE but is not optimum.

�� Other endoscopic therapeutic modalities for Other endoscopic therapeutic modalities for TTT needs further evaluation by larger RCT.TTT needs further evaluation by larger RCT.

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Portal Hypertensive Gastropathy - egfrhep.comPortal Hypertensive Gastropathy Prevalence (Prevalence (22))::--Definite correlation between portal pressure and Definite correlation between