AnnalsofHepatology19(2020)691–693
ContentslistsavailableatScienceDirect
Annals
of
Hepatology
j o ur na l h o me p a g e : w w w . e l s e v i e r . e s / a n n a l s o f h e p a t o l o g y
Brief
Report
Spleen
stiffness
can
be
employed
to
assess
the
efficacy
of
spontaneous
portosystemic
shunts
in
relieving
portal
hypertension
Mauro
Giuffrè
a,b,∗,
Giorgio
Bedogni
b,
Cristiana
Abazia
c,
Flora
Masutti
c,
Claudio
Tiribelli
b,
Lory
Saveria
Crocè
a,b,caDepartmentofMedical,SurgicalandHealthSciences,UniversityofTrieste,Trieste,Italy bItalianLiverFoundation,Basovizza(Trieste),Italy
cLiverClinic,AziendaSanitariaUniversitariaGiuliano-Isontina,CattinaraHospital,Trieste,Italy
a
r
t
i
c
l
e
i
n
f
o
Articlehistory: Received21June2020 Accepted18July2020 Availableonline20August2020
a
b
s
t
r
a
c
t
Introduction:Spleenstiffness(SS)hasbeenfoundtomirrordynamicchangesinportalpressureafter
tran-sjugularintrahepaticportosystemicshunt(TIPS)placement.However,thereisnodataavailableregarding
SSinpatientswithspontaneousportosystemicshunting(SPSS),especiallyinregardstopredictionof
hepaticdecompensation.
Methods:WeretrospectivelyselectedpatientswithconfirmedSPSSandesophagealvarices(EVs)at
endo-scopicexamination,andrecordedanydecompensatingevent(i.e.,varicealhemorrhage,overthepatic
encephalopathy,refractoryascites,spontaneousbacterialperitonitis,hepatorenalsyndrome)inthefirst
twelvemonthsfollowingliverandspleenelastography.
Results:Thepatientswhopresenteddecompensating eventsshowed lowerplateletcount(94.5 vs.
121.5g/L,p<0.001),higherSS(44vs.30kPa,p<0.001),higherprobabilityofEVsaccordingtoSS(77
vs.2%,p<0.001),andhigherspleendiameter(14vs.12cm,p=0.043).Theyalsoshowedahigher
preva-lenceofsplenorenalshunts(66.7vs.31.2%),andasignificantlywiderSPSSmajordiameter(14.5vs.8mm,
p<0.001).
Conclusion:SScouldpredictSPSSefficacyinrelievingportalpressure,andcouldpredictdecompensating
eventsinpatientswithSPSS.
©2020Fundaci ´onCl´ınicaM ´edicaSur,A.C.PublishedbyElsevierEspa ˜na,S.L.U.Thisisanopenaccess
articleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).
1. Introduction
Portal Hypertension (PH), defined as a portal pressure >10−12mmHg, is a common and critical complication of liver cirrhosis,whichdefinesthetransitiontoastageofliverdisease characterizedbyasignificantreducedlifeexpectancyandqualityof life.[1]Generally,PHisassociatedwithincreasedriskofesophageal varices,(EVs)anddecompensatingevents(suchasascites,variceal haemorrhage,andhepaticencephalopathy)[2].Therefore, appro-priatePHquantificationiscrucialandspleenelastographyseems toaddressthisunmetclinicalneed.Despiteitsprovencorrelation withtheinvasivegoldstandardofhepaticvenouspressure gra-dient(HVPG)[3],spleenstiffness(SS)hasbeenfoundtomirror dynamicchangesinportalpressureaftertransjugularintrahepatic portosystemicshunt(TIPS)placement[4,5].
∗ Correspondingauthorat:DipartimentodiScienzeMediche,Chirurgicheedella Salute,UniversitàdiTrieste,StradadiFiume,447,34149Trieste(TS),Italy.
E-mailaddress:gff.mauro@gmail.com(M.Giuffrè).
ThisledustoinvestigatetheroleofSSintheparaphysiological versionofTIPS(i.e.,spontaneousportosystemicshunts,SPSS).In particular,weaimedtodetermineifSScouldhavepredictedthe efficacyofSPSSinrelievingportalpressure,especiallyconsidering thefactthatagroupofpatientswithesophagealvarices(EVs)and withoutcurrent non-selective beta-blockers(NSBB) administra-tionwerenotcorrectlyclassifiedbythespleenstiffnessprobability index,amathematicaldevicethatwehadpreviouslydevelopedin asampleof210cirrhoticpatients[6].Indetail,thisindexprovidesa givenprobabilityofhavingEVsbasedontheindividualvalueofSS, whichcouldalsobeemployedasanon-invasivesurrogateof clin-icallysignificantportalhypertension(CSPH).Surprisingly,inthis groupofpatientstheSSwaseitherloworcomparabletothoseof healthyindividuals[7,8]despitethepresenceofEVsatendoscopy. OfnoticeallpresentedSPSS.
2. Methods
Spleen and Liver Stiffness as well as the laboratory tests reportedin Table 1were performed,as perthe standard clini-https://doi.org/10.1016/j.aohep.2020.07.004
692 M.Giuffrèetal./AnnalsofHepatology19(2020)691–693
Table1
Patientswerestratifiedintwogroupsaccordingtothedevelopmentofdecompensatingeventsintwogroups.Variablearepresentedasabsolutenumber(relativepercentage) ormedian(Quartile1;Quartile3).IntergroupdifferenceswereassessedtroughMann-WhitneyUtestfornumericalvariablesandChi-SquareTestforordinalvariable.SPSS: spontaneousportosystemicshunt;AST(aspartateaminotransferase);ALT(alanineaminotransferase);ALP(alkalinephosphatase);LS(liverstiffness);SS(spleenstiffness); EVs(esophagealvarices).
Total n=52 Patientswithout DecompensatingEvents n=22 Patientswith Decompensating Events N=30 Significance Gender,Male (%) 30(57.7) 14(63.6) 16(53.3) NS Age,years 65(62;68) 65.5(63;69) 64.5(62;67) NS Etiology,N (%) Alcohol Abuse Viral Hepatitis 29(55.8)23(44.2) 15(68.2)7(31.8) 14(46.7) 16(53.3) TypeofSPSS, N(%) Paraumbilical Splenorenal 25(48.1)27(51.9) 15(68.2)7(31.2) 10(33.3) 20(66.7) P=0.013 Cramer’sPhi =0.345 AST(IU/L) 27(23;29.5) 28.5(24.25;31.75) 26(23;28.75) NS ALT(IU/L) 22(20;24) 21.5(19.25;23.5) 22(20;30.75) NS GGT(IU/L) 27(26;39) 27(23.75;36.75) 27.5(26;39) NS ALP(IU/L) 82(80;91) 81.5(80;90) 82(80;97.75) NS TotalBilirubin (mg/dL) 2(1.75;2.20) 1.95(1.60;2.20) 2.04(1.70;2.32) NS Albumin (g/dL) 3.2(2.9;3.4) 3.4(3;3.6) 3.3(2.9;3.6) NS Platelet(g/L) 110(92.75;121) 121.5(115.75;123.75) 94.5(78.25;100) P<0.001 LS(kPa) 42(40;46) 40.5(32.5;43) 45(40.25;47.75) p=0.003 Probabilityof EVsaccording toLS(%) 74(73;75) 73(69;74) 75(74;77) P=0.006 SS(kPa) 39.5(30;45) 30(26.5;32.75) 44(41.25;55) p<0.001 Probabilityof EVsaccording toSS(%) 56(4;81) 2(0.5;11) 77(66;94) p<0.001 SPSS Diameter (mm) 8(11;16) 8(7;10) 14.5(10.25;19) p<0.001 Spleen Diameter(cm) 13(12;15) 12(12;14) 14(12;16) p=0.043
calpractice,onpatientswhowereevaluatedbytheLiverClinic
between January 2018 and December 2018. The methodology
behindelastographymeasurementwasalreadyexplainedindetail
elsewhere[6,8,9].
WeretrospectivelyselectedpatientswithconfirmedSPSSand EVsatendoscopicexamination,andrecordedany decompensat-ingevent(i.e.,varicealhemorrhage,overthepaticencephalopathy, refractoryascites,spontaneousbacterialperitonitis,hepatorenal syndrome)inthefirsttwelvemonthsfollowingelastography exam-ination.
3. Results
Patientswerestratifiedintwogroupsbasedonthedevelopment of decompensatingevents; theircharacteristicsare reported in Table1.Patientswerepredominantlymale(57.5%),withamedian ageof65(62;68)years.Theetiologyofliverdiseasewasalcohol abusein55.8%ofpatientsandvirus-relatedin44.2%ofpatients. Thepatientswhopresenteddecompensatingeventsshowedlower plateletcount(94.5vs.121.5g/L,p<0.001),higherSS(44vs.30kPa, p<0.001), higherprobability ofEVs accordingtoSS (77vs. 2%, p<0.001),and higher spleen diameter(14 vs.12cm, p=0.043). Theyalsoshowedahigherprevalenceofsplenorenalshunts(66.7 vs.31.2%),andasignificantlywiderSPSSmajordiameter(14.5vs. 8mm,p<0.001).
4. Discussion
TheimportanceofthesefindingsresidesinthefactthatSPSS canbeinterpretedasaphysiologicalattemptofthehumanbodyto decompresstheportalvenoussystem.Unfortunately,SPSSoften doesnotallowadequatereductionofportalpressure,whichcan presentelevatedvaluedespitethepresenceofmassiveSPSS[10]. Whatifwecouldemployasimpleand non-invasivemethodto checkifSPSSareeffectivelyaccomplishingtheirpurposeof reduc-ingtheportalpressure?Theanswertothisquestionyieldshigh relevance(giventhefactthatSPSSarerelativelycommoninliver cirrhosis and that theclinical evolution of cirrhoticpatients is extremelyvariable)andcouldfindapossibleanswerinSS, espe-cially because SS hasalready been reportedto predict hepatic decompensation[11].
Theseresults,albeitinteresting,mustbetakenwithcautiondue totherelativelylownumerosityofthesamplesizeandthepossible limitationsrelatedtoselectionbias.Whilewaitingfortheessential externalvalidation,westronglybelievethatSSmaybevaluablein theeverydayclinicalevaluationofcirrhoticpatients.
Authors’contributions
M.Giuffrèetal./AnnalsofHepatology19(2020)691–693 693
F.M.,C.T.andL.S.C.wereinvolvedinthewritingtheoriginaldraft andapprovingthefinalversionofthemanuscript.
Fundingstatement
Theauthorsreceivednospecificfundingforthiswork.
Conflictofinterest
Theauthorshavenoconflictsofinteresttodeclare.
References
[1]D’AmicoG,Garcia-TsaoG,PagliaroL.Naturalhistoryandprognostic indica-torsofsurvivalincirrhosis:asystematicreviewof118studies.JHepatol 2006;44:217–31,http://dx.doi.org/10.1016/j.jhep.2005.10.013.
[2]NorthItalianEndoscopicClubfortheStudyandTreatmentofEsophageal Varices.Predictionofthefirstvaricealhemorrhageinpatientswith cirrho-sisoftheliverandesophagealvarices.NEnglJMed1988;319:983–9,http:// dx.doi.org/10.1056/NEJM198810133191505.
[3]RavaioliF,ColecchiaA,DajtiE,MarascoG,AlemanniLV,TamèM,etal.Spleen stiffnessmirrorschangesinportalhypertensionaftersuccessfulinterferon-free therapyinchronic-hepatitisCviruspatients.WorldJHepatol2018;27:731–42,
http://dx.doi.org/10.4254/wjh.v10.i10.731.
[4]BuechterM,MankaP,TheysohnJM,ReinboldtM,CanbayA,KahramanA.Spleen stiffnessispositivelycorrelatedwithHVPGanddecreasessignificantlyafter TIPSimplantation.DigLiverDis2018;50:54–60,http://dx.doi.org/10.1016/j. dld.2017.09.138.
[5]RanH-T,YeX-P,ZhengY-Y,ZhangD-Z,WangZ-G,ChenJ,etal.Spleenstiffness andsplenoportalvenousflow:assessmentbeforeandaftertransjugular intra-hepaticportosystemicshuntplacement.JUltrasoundMed2013;32(2):221–8,
http://dx.doi.org/10.7863/jum.2013.32.2.221.PublishedOnlineFirst. [6]GiuffrèM,MacorD,MasuttiF,AbaziaC,TinèF, BedogniG,etal. Spleen
StiffnessProbabilityIndex(SSPI):asimpleandaccuratemethodtodetect esophagealvaricesinpatientswithcompensatedlivercirrhosis.AnnHepatol 2020;19:53–61,http://dx.doi.org/10.1016/j.aohep.2019.09.004.
[7]GiuffrèM,MacorD,MasuttiF,AbaziaC,TinèF,PattiR,etal.Evaluationof spleenstiffnessinhealthyvolunteersusingpointshearwaveelastography. AnnHepatol2019;18:736–41,http://dx.doi.org/10.1016/j.aohep.2019.03.004. [8]GiuffrèM,FourakiS,CampigottoM,ColomboA,VisintinA,BuonocoreMR,etal. Alanineaminotransferaseandspleno-portaldynamicsaffectspleenstiffness measuredbypointshear-waveelastographyinpatientswithchronichepatitis Cintheabsenceofsignificantliverfibrosis.JUltrasound2020,http://dx.doi. org/10.1007/s40477-020-00456-9.PublishedOnlineFirst.
[9]GiuffrèM,FourakiS,ComarM,MasuttiF,CrocèLS.Theimportanceof transam-inasesflareinliverelastography:characterizationoftheprobabilityofliver fibrosisoverestimationbyhepatitisCvirus-inducedcytolysis.Microorganisms 2020;8,http://dx.doi.org/10.3390/microorganisms8030348.
[10]HsiehJS,WangJY,HuangCJ,ChenF-M,HuangT-J.Effectofspontaneous por-tosystemicshuntsonhemorrhagefromesophagogastricvarices.WorldJSurg 2004;28:23–8,http://dx.doi.org/10.1007/s00268-003-7068-7.