Ultrasonography for diagnosis of alcoholic cirrhosis in people with alcoholic liver disease

43 Pages·2016·0.6 MB·English

CochraneDatabaseofSystematicReviews
Ultrasonography for diagnosis of alcoholic cirrhosis in people
with alcoholic liver disease (Review)
PavlovCS,CasazzaG,SemenistaiaM,NikolovaD,TsochatzisE,LiusinaE,IvashkinVT,GluudC
PavlovCS,CasazzaG,SemenistaiaM,NikolovaD,TsochatzisE,LiusinaE,IvashkinVT,GluudC.
Ultrasonographyfordiagnosisofalcoholiccirrhosisinpeoplewithalcoholicliverdisease.
CochraneDatabaseofSystematicReviews2016,Issue3.Art.No.:CD011602.
DOI:10.1002/14651858.CD011602.pub2.
www.cochranelibrary.com
Ultrasonographyfordiagnosisofalcoholiccirrhosisinpeoplewithalcoholicliverdisease(Review)
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAINLANGUAGESUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Figure1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Figure2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Figure3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Figure4. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
AUTHORS’CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
CHARACTERISTICSOFSTUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
DATA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Test1.Ultrasonography. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Test2.Irregularoutline(liversurfaceandedgenodularity). . . . . . . . . . . . . . . . . . . . . 30
Test3.Splenomegaly(spleensize). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
Test4.Hepatomegaly. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
Test5.Attenuationoftheultrasoundbeam. . . . . . . . . . . . . . . . . . . . . . . . . . 31
Test6.Parenchymaechogenicity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
Test7.Coarseechopatterns. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
Test8.Finebrightechopatterns. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
Test9.Ascites. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
Test10.Portalhypertension. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
Test11.Rightlobeatrophy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
Test12.Hepaticveinwaveform. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
Test13.Splenicveindiameter. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
ADDITIONALTABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
CONTRIBUTIONSOFAUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
DECLARATIONSOFINTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
SOURCESOFSUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
DIFFERENCESBETWEENPROTOCOLANDREVIEW . . . . . . . . . . . . . . . . . . . . . 40
Ultrasonographyfordiagnosisofalcoholiccirrhosisinpeoplewithalcoholicliverdisease(Review) i
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
[DiagnosticTestAccuracyReview]
Ultrasonography for diagnosis of alcoholic cirrhosis in people
with alcoholic liver disease
ChavdarSPavlov1,2,GiovanniCasazza1,3,MariannaSemenistaia4,DimitrinkaNikolova1,EmmanuelTsochatzis5,EkaterinaLiusina
2,VladimirTIvashkin2,ChristianGluud1
1TheCochraneHepato-BiliaryGroup,CopenhagenTrialUnit,CentreforClinicalInterventionResearch,Department7812,Rigshos-
pitalet, Copenhagen University Hospital, Copenhagen, Denmark. 2Clinic of Internal Diseases Propedeutics, I.M. Sechenov First
MoscowStateMedicalUniversity,Moscow,RussianFederation.3DipartimentodiScienzeBiomedicheeCliniche“L.Sacco”,Univer-
sitàdegliStudidiMilano,Milan,Italy.4I.M.SechenovFirstMoscowStateMedicalUniversity,Moscow,RussianFederation.5Sheila
SherlockLiverCentre,RoyalFreeHospitalandtheUCLInstituteofLiverandDigestiveHealth,London,UK
Contactaddress:ChavdarSPavlov,TheCochraneHepato-Biliary Group,CopenhagenTrialUnit,CentreforClinicalIntervention
Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen, DK-2100, Denmark.
[email protected].
Editorialgroup:CochraneHepato-BiliaryGroup.
Publicationstatusanddate:New,publishedinIssue3,2016.
Reviewcontentassessedasup-to-date: 23September2015.
Citation: PavlovCS,CasazzaG,SemenistaiaM,NikolovaD,TsochatzisE,LiusinaE,IvashkinVT,GluudC.Ultrasonographyfor
diagnosisofalcoholiccirrhosisinpeoplewithalcoholicliverdisease.CochraneDatabaseofSystematicReviews2016,Issue3.Art.No.:
CD011602.DOI:10.1002/14651858.CD011602.pub2.
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
ABSTRACT
Background
Heavyalcoholconsumptioncausesalcoholicliverdiseaseandisacausalfactorofmanytypesofliverinjuriesandconcomitantdiseases.
It is a true systemic disease that may damage the digestive tract, the nervous system, the heartand vascular system, the bone and
skeletalmusclesystem,andtheendocrineandimmunesystem,andcanleadtocancer.Liverdamageinturn,canpresentasmultiple
alcoholicliverdiseases,includingfattyliver,steatohepatitis,fibrosis,alcoholiccirrhosis,andhepatocellularcarcinoma,withpresence
orabsenceofhepatitisBorCvirusinfection.Therearethreescarringtypes(fibrosis)thataremostcommonlyfoundinalcoholicliver
disease: centrilobular scarring, pericellularfibrosis, andperiportalfibrosis. Whenliverfibrosisprogresses, alcoholiccirrhosisoccurs.
Hepatocellularcarcinomaoccursin5%to15%ofpeoplewithalcoholiccirrhosis,butpeopleinwhomhepatocellularcarcinomahas
developedareoftenco-infectedwithhepatitisBorCvirus.
Abstinencefromalcoholmayhelppeoplewithalcoholicdiseaseinimprovingtheirprognosisofsurvivalatanystageoftheirdisease;
however, the more advanced the stage, the higher the risk of complications, co-morbidities, and mortality, and lesser the effectof
abstinence.Beingabstinentonemonthafterdiagnosisofearlycirrhosiswillimprovethechanceofaseven-yearlifeexpectancyby1.6
times.Livertransplantationistheonlyradicalmethodthatmaychangetheprognosisofapersonwithalcoholicliverdisease;however,
besidesthedifficultiesoffindingasuitablelivertransplantorgan,therearemanyotherfactorsthatmayinfluenceaperson’ssurvival.
Ultrasound is an inexpensive method that has been used for years in clinical practice to diagnose alcoholic cirrhosis. Ultrasound
parametersforassessingcirrhosisinpeoplewithalcoholicliverdiseaseencompassamongothersliversize,bluntnessoftheliveredge,
coarsenessoftheliverparenchyma,nodularityoftheliversurface,sizeofthelymphnodesaroundthehepaticartery,irregularityand
narrownessoftheinferiorvenacava,portalveinvelocity,andspleensize.
Diagnosisofcirrhosisbyultrasound,especiallyinpeoplewhoareasymptomatic,mayhaveitsadvantagesfortheprognosis,motivation,
andtreatmentofthesepeopletodecreasetheiralcoholconsumptionorbecomeabstinent.
Ultrasonographyfordiagnosisofalcoholiccirrhosisinpeoplewithalcoholicliverdisease(Review) 1
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Timelydiagnosisofalcoholiccirrhosisinpeoplewithalcoholicliverdiseaseisthecornerstoneforevaluationofprognosisorchoosing
treatmentstrategies.
Objectives
Todeterminethediagnostic accuracyofultrasonography fordetectingthepresenceorabsenceofcirrhosisinpeoplewithalcoholic
liverdiseasecomparedwithliverbiopsyasreferencestandard.
Todeterminethediagnosticaccuracyofanyoftheultrasonographytests,B-modeorecho-colourDopplerultrasonography,usedsingly
orcombined,orplusultrasonographysigns,oracombinationofthese,fordetectinghepaticcirrhosisinpeoplewithalcoholicliver
diseasecomparedwithliverbiopsyasareferencestandard,irrespectiveofsequence.
Searchmethods
We performed searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Hepato-Biliary Group
DiagnosticTestAccuracyStudiesRegister,TheCochraneLibrary(Wiley),MEDLINE(OvidSP),EMBASE(OvidSP),andtheScience
CitationIndexExpandedto8January2015.Weappliednolanguagelimitations.
Wescreenedstudyreferencesoftheretrievedstudiestoidentifyotherpotentiallyrelevantstudiesforinclusioninthereviewandread
abstractandposterpublications.
Selectioncriteria
Threereviewauthorsindependentlyidentifiedstudiesforpossibleinclusioninthereview.Weexcludedreferencesnotfulfillingthe
inclusioncriteriaofthereviewprotocol.Wesente-mailstostudyauthors.
Theincludedstudieshadtoevaluateultrasoundinthediagnosisofhepaticcirrhosisusingonlyliverbiopsyasthereferencestandard.
Themaximumtimeintervalofinvestigationwithliverbiopsyandultrasonographyshouldnothaveexceededsixmonths.Inaddition,
ultrasonographycouldhavebeenperformedbeforeorafterliverbiopsy.
Datacollectionandanalysis
WefollowedtheCochraneHandbookforSystematicReviewsofDiagnosticTestAccuracy.
Mainresults
Thereviewincludedtwostudiesthatprovidednumericaldataregardingalcoholiccirrhosisin205menandwomenwithalcoholicliver
disease.Althoughtherewerenoapplicabilityconcernsintermsofparticipantselection,indextext,andreferencestandard,wejudged
thetwostudiesathighriskofbias.Participantsinbothstudieshadundergonebothliverbiopsyandultrasonographyinvestigations.
Thestudiessharedonlyafewcomparableclinicalsignsandsymptoms(indextests).
Wedecidedtonotperformameta-analysisduetothehighriskofbiasandthehighdegreeofheterogeneityoftheincludedstudies.
Authors’conclusions
Asthe accuracy of ultrasonography in thetwo included studies was not informative enough, we couldnot recommendthe use of
ultrasonographyasadiagnostictoolforlivercirrhosisinpeoplewithalcoholicliverdisease.Inordertobeabletoanswerthereview
questions,weneeddiagnosticultrasonographyprospectivestudiesofadequatesamplesize,enrollingonlyparticipantswithalcoholic
liverdisease.
ThedesignandreportofthestudiesshouldfollowtheStandardsforReportingofDiagnosticAccuracy.Thesonographicfeatures,with
validatedcut-offs, whichmayhelpidentify clinicalsignsusedfordiagnosis offibrosisinalcoholicliverdisease,shouldbecarefully
selectedtoachievemaximumdiagnosticaccuracyonultrasonography.
PLAIN LANGUAGE SUMMARY
Ultrasonographyfordiagnosisofalcoholiccirrhosisinpeoplewithalcoholicliverdisease
Background
Ultrasonographyfordiagnosisofalcoholiccirrhosisinpeoplewithalcoholicliverdisease(Review) 2
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Heavyalcoholconsumptioncausesalcoholicliverdiseaseandmayleadtoanumberofotherconcomitantdiseases.Alcoholmaydamage
thefunctionofbodyorgansandcancausecancer.Liverdamageduetoexcessivealcoholconsumptionisusuallypresentedasfattyliver
(build-upoffatsintheliver),steatohepatitis(inflammationoftheliverwithconcurrentfataccumulationintheliver),fibrosis(fibrous
degeneration),alcoholiccirrhosis(scarringoftheliver),andhepatocellularcarcinoma(mostcommontypeoflivercancer).Whenliver
fibrosisprogresses,alcoholiccirrhosisoccurs.
Abstinencefromalcoholmayhelppeoplewithalcoholicdiseasetoimprovetheirhealthatanystageoftheirdisease;however,themore
advancedthestage,thehighertheriskofcomplications,co-morbidities(presenceofotherdiseases),andmortality(death),andlesser
theeffectofabstinence.Abstinencefromalcoholonemonthafterdiagnosisofearlycirrhosiswillimprovethechanceofaseven-year
lifeexpectancyby1.6times.Livertransplantation (replacementofadiseasedliver)istheonlyradicalmethodthatmaychangethe
prognosisofapersonwithalcoholicliverdisease;however,besidesthedifficultiesoffindingasuitablelivertransplantorgan,thereare
manyotherfactorsthatmayinfluenceaperson’ssurvivalaftertransplantation.
Ultrasound is an inexpensive method that has been used for years in clinical practice to diagnose alcoholic cirrhosis. Ultrasound
parametersforassessingcirrhosisinpeoplewithalcoholicliverdiseaseencompassamongothersliversize,bluntnessoftheliveredge,
coarsenessoftheliverparenchyma(partoftheliverthatfiltersbloodtoremovetoxins),nodularity(unevenness)oftheliversurface,size
ofthelymphnodes(smallglandsthatfilterlymph)aroundthehepaticartery(whichsuppliesoxygenatedbloodtotheliver),irregularity
andnarrownessoftheinferiorvenacava(whichcarriesbloodfromthelowerbodytotheheart),portalveinvelocity,andspleensize.
Diagnosisofcirrhosisbyultrasound,especiallyinpeoplewhohavenosymptoms,mayhaveitsadvantagesfortheprognosis,motivation,
andtreatmentofthesepeopletodecreasetheiralcoholconsumptionorbecomeabstinent.
Timely diagnosis of alcoholic cirrhosis in people with alcoholic liver disease is important for evaluation of prognosis or choosing
treatmentstrategies.
Aim
Theprimaryreviewaimwastodeterminethediagnosticaccuracyofultrasoundfordetectingthepresenceorabsenceofcirrhosisin
peoplewithalcoholicliverdiseasecomparedwithliverbiopsy(whereasmallneedleisinsertedintothelivertocollectasample,which
isthenexaminedinalaboratory)asreferencestandard(i.e.,thebestavailabletest).Thesecondaryaimofthereviewwastodetermine
thediagnosticaccuracyofanyoftheultrasoundtests,B-mode(atwo-dimensionalultrasoundimagedisplaycomposedofbrightdots
representingtheultrasoundechoes)orecho-colourDopplerultrasound(acolourultrasoundimageshowingbloodflowthroughthe
liver),used singly or combined, or plus ultrasound signs, or acombination of these,for detecting hepaticcirrhosisin people with
alcoholicliverdiseasecomparedwithliverbiopsyasareferencestandard.
Methods
Wesearchedthemedicalliteraturetoretrievestudiesforthereviewto8January2015.
Results
Weidentifiedtwostudies;onefrom1985,performedinFrance,andtheotherfrom2013,performedinSouthKorea.Wecouldnot
analyse the data asthe two studies with 205 participants in total were very differentand theysharedonly a fewclinical signs and
symptomsforassessmentofcirrhosis.Weconsideredthestudiesathighriskofbias(thequalityoftheevidencewaslow).
Funding
OneofthetwostudieswassponsoredbyagrantfromtheMinistryofHealthandWelfare,RepublicofKorea.
Conclusions
Thereviewauthorscannotrecommendtheuseofultrasoundasadiagnostictoolforlivercirrhosisinpeoplewithalcoholicliverdisease
astheobtainedstudydatawereinsufficientforanalysis.Diagnosticultrasoundprospectivestudieswithalargenumberofpeopleand
similar signs andfeatureson ultrasound imaging are neededtoestablish how good thetestisin detectingcirrhosis inpeople with
alcoholicliverdisease.
Ultrasonographyfordiagnosisofalcoholiccirrhosisinpeoplewithalcoholicliverdisease(Review) 3
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
BACKGROUND size,betooheterogeneous,orlacksufficientevidenceforbenefits.
Withoutdiminishingnutritionalandsupportivemanagementof
Alcoholconsumptionisaworldwideproblem.Everyyearapprox-
peoplewithalcoholicliverdisease,completeabstinencefromal-
imately2.5millionpeopledieofit;320,000ofthemareyoung
coholseemsstilltobetheonlyrecommendedformofhepatopro-
people between 15 and 29 years of age. Based on estimates for
tection.
2004,alcoholwasresponsibleforalmost4%ofalldeathsinthe
world(WHO2010). Ultrasoundisaninexpensivemethodthathasbeenusedforyears
inclinicalpracticetodiagnosealcoholiccirrhosis(Rockey2009;
Heavyalcoholconsumption causesalcoholicliverdisease andis
O’Shea 2010). Ultrasound parameters for assessing cirrhosis in
a causal factor of many types of liver injuries and concomitant
peoplewithalcoholicliverdiseaseencompassamongothersliver
diseases.Itisatruesystemicdiseasethatmaydamagethedigestive
size,bluntnessoftheliveredge,coarsenessoftheliverparenchyma,
tract,thenervoussystem,theheartandvascularsystem,thebone
nodularity of the liver surface, size of the lymph nodes around
andskeletalmusclesystem,andtheendocrineandimmunesystem,
thehepaticartery,irregularityandnarrownessoftheinferiorvena
andcanleadtocancer(WHO2010;Rocco2014).
cava,portalveinvelocity,andspleensize(Nishiura2005).
Liverdamageinturn,canpresentasmultiplealcoholicliverdis-
eases,includingfattyliver,steatohepatitis,fibrosis,alcoholiccir- Inaseriesof1604peoplewithalcoholicliverdiseasediagnosedon
rhosis,andhepatocellularcarcinoma,withpresenceorabsenceof liverbiopsyorclinicallyconfirmeddiagnosis,608(38%)people
hepatitisBorCvirusinfection(Brunt1974;Bruha2012;Testino haddevelopedalcoholiccirrhosis(Naveau1997).Diagnosisofcir-
2014).Therearethreescarringtypes(fibrosis)thataremostcom- rhosisbyultrasound,especiallyinpeoplewhoareasymptomatic,
monlyfoundinalcoholicliverdisease:centrilobularscarring,peri- mayhaveitsadvantagesfortheprognosis,motivation,andtreat-
cellularfibrosis, and periportalfibrosis. Whenliverfibrosispro- ment of these people to decrease their alcohol consumption or
gresses, alcoholiccirrhosis occurs. Hepatocellular carcinoma oc- becomeabstinent(O’Shea2010).
cursin5%to15%ofpeoplewithalcoholiccirrhosis,butpeople
Timely diagnosis of alcoholic cirrhosis in people with alcoholic
in whom hepatocellular carcinoma has developed are often co-
liverdiseaseisthecornerstoneforevaluationofprognosisorchoos-
infectedwith hepatitis B or Cvirus (MacSween 1986; Jaurigue
ingtreatmentstrategiesinthesepeople.
2014).
Abstinencefromalcoholmayhelppeoplewithalcoholicdisease
inimprovingtheirprognosisofsurvivalatanystageoftheirdis-
Targetconditionbeingdiagnosed
ease;however,themoreadvancedthestage,thehighertheriskof
complications,co-morbidities,andmortality,andlessertheeffect
ofabstinence(Borowsky1981).Beingabstinentonemonthafter
diagnosisofearlycirrhosiswillimprovethechanceofaseven-year Cirrhosisinpeoplewithalcoholicliverdisease
lifeexpectancyby1.6times(Verrill2009).Livertransplantation
Peoplewithalcoholicliverdiseaseareatriskofdevelopingliver
istheonlyradicalmethodthatmaychangetheprognosisofaper-
fibrosisandcirrhosis.Thisriskisconsideredhigherinpeoplewho
son with alcoholicliverdisease; however,besidesthedifficulties
are binge drinkers, peoplewith increasedserumalanine amino-
offindingasuitablelivertransplantorgan,therearemanyother
transferase and aspartate aminotransferase levels, and in people
factors that may influence a person’s survival (Iruzubieta 2013;
withseverealcoholhepatitisonliverbiopsy(Bouchier1992).Cir-
Singal2013).
rhosismayhavesymptomsandsignsofliverdisease,andcirrhosis
Cochranesystematicreviewsofrandomisedclinicaltrialsofphar- mayvaryfromonepersontoanother.Ingeneral,peoplewithalco-
macologicalinterventionsusedforreducingalcoholconsumption holicliverdiseaseseeadoctorwhensymptomsandsignsfromthe
such as acamprosate, benzodiazepines, naltrexone, gamma-hy- complicationsofcirrhosishavealreadydeveloped(O’Shea2010).
droxybutyrate,baclofen(derivativeofgamma-aminobutyricacid), Physiciansshouldattempttomotivatepeopletostopdrinking.In-
andanticonvulsantsversusplacebooranotherdruginalcohol-de- directevidenceofalcoholabusecanbecollectedthroughquestion-
pendentpeoplehavestudiedthebenefitsandharmsoftheseinter- nairesaboutdrinkinghabits,throughinformationreceivedfrom
ventionsforalcoholreductionorwithdrawal(Amato2010;Leone family members, and through running laboratory tests(O’Shea
2010; Minozzi 2010; Rösner 2010a; Rösner 2010b; Liu 2013; 2010).
Pani2014).However,theconclusions,despiteshowingsomepo- Hepatic fibrosis may developas a result of weekly alcohol con-
tentialtendencyofalcoholreductionorpromotionofabstinence, sumptionofsevento13beveragesforwomen(onebeverage=12
lack the desired robustness of evidence as the performed ran- gofalcohol)and14to27beveragesformenoverthecourseof
domisedclinicaltrialsforalcoholwithdrawalwiththesuggested fiveormoreyears(Savolainen1993;Becker1996).Theriskratio
drug interventions may fail in quality, be of insufficient sample ofprogressionoffibrosistocirrhosisincreasessignificantlywitha
Ultrasonographyfordiagnosisofalcoholiccirrhosisinpeoplewithalcoholicliverdisease(Review) 4
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
dailyconsumptionof20to40gofethanolinwomenandmore referthereaderstothelasttworowsofthetable(shaded).
than80gofethanolinmen(Sherlock1997;O’Shea2010).
Theliveristhemain siteofalcoholmetabolismacting through
twohepaticenzymes,alcoholdehydrogenaseandcytochromeP- Indextest(s)
450(CYP)2E1.Increasedalcoholintakedisruptsmetabolicliver
Ultrasonographyisusedinclinicalpracticefordiagnosisofcirrho-
function,and,asaresult,alcoholicliverdiseasedevelops(Stewart
sisinpeoplewithalcoholicliverdiseaseasitallowsinvestigation
2001).
ofthehepatictissuethroughthegenerationofultrasonicwaves.
METAVIRisthemostwidelyusedscoringsystemforinterpreta-
B-mode and Echo-colour Doppler ultrasonography seem to be
tionofliverbiopsyresultsbasedonthestageoffibrosiswhereF0
themostoftenusedmethodsfordiagnosisofcirrhosis.Thereare
indicatesnofibrosis,F1indicatesportalfibrousexpansion(mild
someothernewultrasound-based methods,such asultrasound-
fibrosis),F2indicatesthinfibrousseptaemanatingfromportaltri-
basedelastography,acousticradiationforceimpulse(ARFI),and
ads(significantfibrosis),F3indicatesfibrousseptabridgingportal
supersonicshearimaging.
triadsandcentralveins(severefibrosis),andF4indicatescirrhosis
Ultrasonicpatternsobtainedatultrasonography investigationin
(Table1).
B-mode areusually classifiedaspositive or negative considering
Michalak 2003 validated the reproducibility of the METAVIR
signs usedin differentcombinations and definedas indices, for
scoreusingaslightlymodifiedMETAVIRscore,thatis,theportal
example,parenchymal(liversurface,volume,edge,andtexture),
tract/septalfibrosisscore,toinvestigatetheamountoffibrosisand
extrahepatic(spleenvolume,presenceofascites),andvascular(di-
studytheinfluenceofcentrilobularfibrosisandportaltract/septal
ameterofportalandspleenveins).Hepaticfibrosisproducesab-
fibrosis inalcoholicchronicliverdisease. Theamount of portal
normalechopatternsonultrasoundscanning.Muchhigheratten-
tract/septalfibrosis inpeoplewith alcoholicchronicdisease was
uationisobservedatexaminationoftheliverofpeoplewithsteato-
greater than the amount of centrilobular fibrosis in the control
siscomparedtotheliverofpeoplewithhepaticfibrosis(Bamber
group of people with viral chronichepatitisdisease, which sug-
1979;Saverymuttu1986).
gestedthatportaltract/septalfibrosiswasmorefrequentinalco-
Vascular(Doppler)indices,suchasDopplerperfusionindex,hep-
holicchronicliverdiseasethaninviralchronichepatitis.However,
atictransittime,portalveincongestiveindex,andvariousratios
centrilobularfibrosisformswiththeadvanceoffibrosisincirrho-
analysing different blood vessels, are used indirectly for detec-
sis.TheprognosticvalueoftheMETAVIRfibrosisscoreinalco-
tionofportalhypertensionandcirrhosis(Ersoz1999;Hizli2010;
holicliverdiseasestillneedstobeestablished(Michalak2003).
Ivashkin2011a).
InTable1,wehaveincludedotherwidelyusedsystemsforclassi-
ficationoffibrosisinpeoplewithalcoholicliverdisease(Knodell
1981; Desmet 1994; Ishak 1995; Brunt 1999; Kleiner 2005;
Haque2010).However,asthefocusofourreviewisonalcoholic Clinicalpathway
cirrhosisalone,fordiscrepanciesinclassificationofcirrhosis,we
Figure1presentstheclinicalpathwayinthediagnosisofalcoholic
livercirrhosis.
Ultrasonographyfordiagnosisofalcoholiccirrhosisinpeoplewithalcoholicliverdisease(Review) 5
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Figure1. Clinicalpathwayinthediagnosisofalcoholicliverdisease.
Ultrasonographyfordiagnosisofalcoholiccirrhosisinpeoplewithalcoholicliverdisease(Review) 6
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Alternativetest(s)
andhaemorrhage.Liverbiopsycanbepainful,time-consuming,
Differentmethodstoassessliverfibrosishavebeendevelopedsince andstressfulfortheperson(Grant1999;O’Shea2010;Ivashkin
1990. Most of them are aimed at quantifying the elasticity or 2011b).Theriskofhaemorrhageanddeathafterapercutaneous
viscoelasticityofthelivertissue.Therearetwocommonelements liverbiopsyisespeciallyhigherinpeoplewithaplateletcountof
ineveryelasticityimagingmethod:aforceorstressisappliedon 60,000 per mm3 or less (Seeff 2010). Transjugular liver biopsy
thelivertissueandtheobtainedmechanicalresponseismeasured. seems a safer alternative for people with low platelet counts or
ARFI(ACUSONS2000;SiemensLtd.)isanon-invasiveimaging clottingabnormalities.Thesmallsizeofthetissuesamples,either
techniquethatcandetectandquantifyhepaticfibrosis.TheARFI obtainedtranscutaneouslyorviathetransjugularroute,mayalso
technologyisalsocalledliverultrasoundelastography(Iyo2009). leadtosamplingerrors.
ARFIimagingisfasterthanconventionalmethodsasARFIuses Thetechnicalpossibilitiesoftheultrasonographyequipmentand
higher frequencies that are comparable to those used in colour theindividualexperienceoftheinvestigatorperformingtheultra-
Dopplerimaging.Theimageshavegreatercontrastandthebound- sonographyarethemainfactorsinfluencingtheprecisionofthe
aryofthefocallesionsarebetterdefinedcomparedwithconven- ultrasoundexamination.Consensusonusingultrasonographyas
tionalultrasonographyimaginingtechniques(Iyo2009). a non-invasive methodfor diagnosis of cirrhosis in people with
Supersonic shear imaging investigates tissue elasticity to detect alcoholicliverdiseaseseemsnottohavebeenestablished,despite
hepaticfibrosisandsteatosis.Itisbasedonvelocityestimationof being widely used instead of, or together with, other non-inva-
ashearwave,generatedbyaradiationforce(Bercoff2004). sivetechniques(Shiha2009).Whenapersonpresentswithclini-
Magnetic resonance elastography combines magnetic resonance calsymptoms(e.g.,ascites,encephalopathy,oesophagealbleeding)
imaging with sound waves to create a visual map (elastogram) ofcirrhosis,neitherliverbiopsynorultrasonographyareneeded.
showingthestiffnessofthelivertissue.Itisusedprimarilytodetect However,incaseofinsufficientorunclearexpressionofclinical
hardeningofthelivercausedbydifferenttypesofliverdiseases, signs,await-and-seeapproach,ultrasonography,orotheralterna-
includingthoseofalcoholicaetiology(Yin2007). tivenon-invasivetestsmaybeconsideredbeforearrangingaliver
Transientelastographyisanothernon-invasivemethodforassess- biopsyinvestigation(Figure1).Ascirrhosisisamainprognostic
mentofhepaticfibrosis(Gómez-Domínguez2006;Pavlov2015), variablewithimpactonsurvivalofpeoplewithalcoholicliverdis-
whichmeasureshepaticfibrosisthroughthestiffnessofthehepatic ease,itisimportanttodetectcirrhosis,assesstheriskofcomplica-
parenchyma.Transientelastographymeasuresthespeedofprop- tions,andencourageabstinenceofdrinkingalcohol(Leong2012;
agationoftheelasticwavethroughthehepaticparenchyma:the Singal2013;Testino2014).
stifferthetissue,thefastertheshearwavepropagatestheobtained Thisreviewaimedtometa-analyse datafromstudiesonthedi-
hepaticstiffness,expressedasamedianvalueinkiloPascals(kPa). agnosis ofcirrhosisinpeoplewithalcoholicliverdisease andto
Other alternative non-invasive tests (apart from venepuncture) assessthediagnosticaccuracyofultrasonographyindetectingthe
are laboratory tests such as aspartate aminotransferase to ala- presenceofcirrhosiscomparedwithliverbiopsyasreferencestan-
nine aminotransferase ratio, plateletcount, prothrombin index, dard,followingCochranemethodology(SRDTAHandbook).
hyaluronicacid,andenhancedliverfibrosisscore(Crespo2012; Wedidnotidentifyanymeta-analysisorsystematicreviewonthe
Liu2012).Allofthesetestsareusedassurrogatemarkersforstag- use of ultrasonography for defining the presence of cirrhosis in
ingofhepaticfibrosis.Inaddition,differentcombinationsofbio- peoplewithalcoholicliverdisease.ACochranesystematicdiag-
chemicaltestssuchasFibroTest®andFibrometre®areusedfor nostic testaccuracy review on ultrasonography in detecting cir-
diagnosisandstagingofhepaticfibrosisinpeoplewithalcoholic rhosisinpeoplewithalcoholicliverdiseasecomparedwithliver
liverdisease(Morra2007;Poynard2007;Poynard2008;Angulo biopsydoesnotexisteither.Therefore,weconductedthisreview.
2009).
Rationale
OBJECTIVES
Liverbiopsyhassofarbeenconsideredthestandardmethodfor
detectionofhepaticfibrosisanditsstaging,usingdifferentsemi- Todeterminethediagnosticaccuracyofultrasonographyforde-
quantitativemorphologicalscoresonlivertissuesampleswithasize tectingthepresenceorabsenceofcirrhosisinpeoplewithalcoholic
ofnomorethan1to2cm3(Table1).Oneadvantageofliverbiopsy liverdiseasecomparedwithliverbiopsyasreferencestandard.
is that it may give diagnostic information for concurrent liver
diseases(Poulsen1979;Ismail2011).However,thereareanumber
ofdisadvantageswithliverbiopsy.Itisinvasive,anditmayhave
Secondaryobjectives
potentialriskstothepersonsuchaspuncturesofabdominalorgans
Ultrasonographyfordiagnosisofalcoholiccirrhosisinpeoplewithalcoholicliverdisease(Review) 7
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Todeterminethediagnosticaccuracyofanyoftheultrasonogra- Participants
phytests,B-modeorEcho-colourDopplerultrasonography,used
Participantsofanysexandethnicorigin,over16yearsold,and
singlyorcombined,orplusultrasonographysigns,oracombina-
diagnosed with alcoholic liver disease, following study authors’
tionofthese,fordetectinghepaticcirrhosisinpeoplewithalco-
statements.Theparticipantscouldhavebeenhospitalisedorman-
holicliverdiseasecomparedwithliverbiopsyasareferencestan-
agedasoutpatients.
dard,irrespectiveofsequence.
Thediagnosis ofalcoholicliverdiseaseinthestudyparticipants
Incaseofdiscrepanciesintheresults,weplannedtoexplorehet-
should have been established based on registered history of ex-
erogeneityanalysing:
cessivealcoholintakeofsufficientdurationandquantitytogether
• liverbiopsyasthereferencestandard:
withclinicalevidenceofliverdiseaseexpressedwithphysicalsigns
◦ differentgradeofinflammation(amountofongoing
atexaminationandfollowedbylaboratoryevidenceofliverdis-
inflammationandnecrosis)accordingtotheliverbiopsy(below
ease.Toascertainthediagnosisofalcoholicliverdiseaseandstudy
twogradescomparedtotwoorgreatergradesofactivity);
the presence or absence of cirrhosis, both ultrasonography and
◦ differentlengthsofliverbiopsysample(shorterthan
liver biopsy should have beenperformed, irrespective of the se-
15mmcomparedto15mmorlonger)ornumberofportal
quence.
tracts(fewerthansixcomparedtosixormore),asreportedinthe
We planned to also include participants if suspected of having
studies;
non-alcoholicfattyliverdisease,inadditiontodiagnosedalcoholic
◦ percutaneousliverbiopsyversustransvenous
liverdisease.
(transjugular)liverbiopsyversuslaparoscopicliverbiopsy;
Wedidnotconsiderforinclusionpeoplediagnosedwithalcoholic
• differenttechnicalcharacteristicsoftheultrasonography
liverdiseaseandhavingaconcomitantliverdiseasesuchaschronic
equipment(e.g.,differenttransducers,differentwavelengths);
hepatitisCvirusinfection,chronichepatitisBvirusinfection,au-
• differentskillsoftheoperatorasstatedbytheauthors;
toimmuneliverdisease,orhumanimmunodeficiencyvirus(HIV)
• completeabstinent(teetotalers)ornon-abstinentstudy
infection.Weextracteddataonstudyparticipantswithalcoholic
participants(asdefinedintheincludedstudies).
liverdiseasealonewheneversuchdatawereavailableinthestudy
reportorwheneverwecouldobtainthedatarequiredforthere-
Inaddition,weattemptedtoidentifythemostaccurateultrasono-
viewthroughpersonalcommunicationwithstudyauthors.Inthe
graphictestsandindicesfordiagnosisofcirrhosisinpeoplewith
lattercase,wedisregardedsomeofthedatapresentedinthepub-
alcoholicliverdisease.
licationandusedthedataprovidedbythestudyauthorsthrough
personalcommunication.
Indextests
METHODS
Ultrasonographyinanymode.
Asweexpectedthatstudyauthorswouldhaveuseddifferentmea-
surements,signs,andcombinationsofsignsforassessmentofcir-
rhosis by ultrasonography with different techniques and mode,
Criteriaforconsideringstudiesforthisreview
wedidnotspecifythesehereinadvance.However,weconsidered
parenchymal,vascular,andextrahepaticultrasonographicsignsas
differentindextests.
Typesofstudies
Diagnosticcohortstudydesignsanddiagnosticcase-controlstudy Targetconditions
designsthatassessedalcoholiccirrhosisinpeoplewithalcoholic
TherearefivestagesofliverfibrosisbyMETAVIR(Table1):
liverdisease through ultrasonography and liverbiopsy, irrespec- • F0=nofibrosis;
tiveoflanguageorpublicationstatus,orwhetherdatawerecol- • F1=mildfibrosis;
lectedprospectivelyorretrospectively.Weplannedtoincluderan- • F2=significantfibrosis;
domisedclinicaltrialsorcontrolledclinicalstudieshadtheyful- • F3=severefibrosis;
filledtheinclusioncriteriaofourreviewprotocol. • F4=cirrhosis.
Weincludedstudiespublishedasfullpaperarticles,intheform
ofabstractspublishedinconferenceproceedings,orpresentedas The target condition is thepresence of cirrhosis in people with
postersifanyofthesewereidentifiedwiththesearches. alcoholicliverdisease,definedusingtheMETAVIRscore.
Wealsoconsideredstudiesiftheyhadincludedparticipantswith Thus,wedichotomisedthefibrosisestimatedbytheMETAVIR
differentaetiologiesofliverdisease. scoreasfollows:weconsideredpeoplewithaMETAVIRscoreof
Ultrasonographyfordiagnosisofalcoholiccirrhosisinpeoplewithalcoholicliverdisease(Review) 8
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.