the efficacy of aspartate aminotransferase-to-(1)

8/20/2019 The Efficacy of Aspartate Aminotransferase-To-(1)

http://slidepdf.com/reader/full/the-efficacy-of-aspartate-aminotransferase-to-1 1/7

Original articleKorean J Pediatr 2013;56(1):19-25ttp://dx.doi.org/10.3345/kjp.2013.56.1.19 p !!" 1#3$-1061% e !!" 2092-#25$ Korean J Pediatr

&'e e((i a * o( a+partate a,inotran+(era+e-to- p ate et ratio index or a++e++ing 'epati i ro+i+in 'i d'ood nona o'o i +teato'epatiti+ or ,edi a pra ti e/ar- Ki,0 102

0 nkoo Kang0 1020

50 !e ng,in 6a'n0 1020

50 i J ng 7ee0 203

0 o ng "* n Park0 40 6ong Ko'0

102

1

2

3

4

Purpose: Childhood obesity is associated with nonalcoholic fatty liver disease (NAFLD), and it hasbecome one of the most common causes of childhood chronic liver diseases which signicant as acause of liver related mortality and morbidity in children in the United States. The development ofsimplerandeasierclinicalindicesformedicalpracticeisneededtoidentifyadvancedhepaticbrosisin childhood NAFLD instead of invasive method like liver biopsy. FibroScan and aspartate aminotransferase (AST)toplatelet ratio index (APRI) have been proposed as a simple and noninvasivepredictor to evaluate hepatic brosis in several liver diseases. APRI could be a good alternative todetectpathologicchangeinchildhoodNAFLD.ThepurposeofthisstudyistovalidatetheefficacyofAPRIforassessinghepaticbrosisinchildhoodNAFLDbasedonFibroScan.Methods: Thisstudyincluded23childrenwithNAFLDwhounderwentFibroScan.Clinical,laboratoryandradiologicalevaluationincludingAPRIwasperformed.Toconrm theresultofthisstudy,6patients

receivedliverbiopsy.Results: Factorsassociatedwithhepaticbrosis(stiffnessmeasurement>5.9kPaFibroscan)weretriglyceride, AST, alanine aminotransferase, platelet count, APRI and collagen IV. In multivariateanalysis,APRIwerecorrelatedwithhepaticbrosis(>5.9kPa).Inreceiveroperatingcharacteristicscurve, APRI of meaningful brosis (cutoff value, 0.4669; area under the receiver operating characteristics,0.875)presentedsensitivityof94%,specicityof66%,positivepredictivevalueof94%,andnegativepredictivevalueof64%.Conclusion: APRImightbeanoninvasive,simple,andreadilyavailablemethodformedicalpracticetopredicthepaticbrosisofchildhoodNAFLD.

Keywords: Nonalcoholicfattyliverdisease,Hepaticbrosis,APRI,Child

Introduction

&'e 8or d 8ide in rea+e in 'i d'ood o e+it* i+ a +igni i ant pro e,. e+it* i+

a++o iated 8it' nona o'o i att* i er di+ea+e (" <7 ) 8'i ' 'a+ e o,e one o t'e ,o+t o,,on a +e+ o 'i d'ood 'roni i er di+ea+e+ in t'e =nited !tate+

1).

" <7 repre+ent+ a gro p o di+ea+e+ ranging ro, a+*,pto,ati +i,p e att* i er to nona o'o i +teato'epatiti+ (" ! ) 'ara teri>ed * t'e 'i+to ogi a e iden e

Correspondingauthor: HongKoh,MDDepartmentofPediatrics,SeverancePediatricLiverDiseaseGroup,SeveranceChildren’sHospital,YonseiUniversityCollegeofMedicine,50Yonseiro,Seodaemungu,Seoul120752,KoreaTel:+82222282053Fax:+8223939118Email:[email protected]*Theseauthorscontributedequallytothisstudy.

Received:21February2012Revised:30April2012Accepted:2August2012

?op*rig't @ 2013 * &'e Korean Pediatri !o iet*

&'i+ i+ an open-a e++ arti e di+tri ted nder t'eter,+ o t'e ?reati e ?o,,on+ ttri tion "on-?o,,er ia 7i en+e ('ttp:// reati e o,,on+.org/

i en+e+/ *-n /3.0/) 8'i ' per,it+ nre+tri ted non-o,,er ia +e di+tri tion and reprod tion in an*

,edi , pro ided t'e origina 8ork i+ proper * ited.

ttp://dx.doi.org/10.3345/kjp.2013.56.1.19 19

E Kim,et al. % Efcacy o APRI in childhood NASH

Department of Pediatrics, Yonsei University College of Medicine, Seoul,Severance Pediatric Liver Disease roup, Severance C!ildren"s #ospital, Seoul, Department of Diagnostic $adiology, $esearc! %nstitute of $adiologic Science, Yonsei University College of Medicine, Seoul, Department of Pat!ology, Yonsei University College of Medicine, Seoul, &orea



o apopto+i+/in a,,ation/ i ro+i+ and to r*ptogeniirr'o+i+

2). " <7 i+ a +o i,portant a+ a a +e o i er-re ated

,orta it* and ,or idit*. &'ere(ore ear * identi(i ation o( i ro+i+ in 'i dren i+ r ia

3). ? rrent * i er iop+* i+ t'e go d

+tandard a++e++,ent ,et'od to in e+tigate 'epati i ro+i+ andin a,,ation. o8e er d e to t'e in a+i ene++ o i er io- p+* it ,a* not e re o,,ended or +e in 'i dren. +o it i+

'a enging to +e i er iop+* a+ a reoperation or t'erape ti

and

o o8- p p rpo+e+

4 5)

.

&'ere ore

an

a rate

nonin a+i e pro ed re to dete t t'e degree o 'epati i ro+i+ in " <7i+ needed. nonin a+i e rapid pain e++ and reprod i ete 'niA e tran+ient e a+tograp'* (<i ro! an 'o+en+ Pari+<ran e) 'a+ een de e oped to ,ea+ re i er +ti ne++

6). 7i er

+ti ne++ and t'e +e erit* o i er i ro+i+ in patient+ 8it' " <7 'a e a +igni i ant and po+iti e orre ation 8it' t'ere+ t+ o i er iop+ie+. &' + <i ro! an an e a +e ando je ti e ,et'od to a++e++ t'e degree o i er i ro+i+ in " <7 patient+

#). o8e er t'e 'ig' o+t o <i ro! an eA ip,ent and

t'e need o +ki +pe ia i+t+ i,it it+ road +e e+pe ia * in,edi a pra ti e+

$). <or t'i+ rea+on t'e de e op,ent o +i,p er

and ea+ier ini a and a orator* indi e+ or ,edi a pra ti eare needed to identi * ad an ed i ro+i+ in patient+ 8it' " 7< . &'e a+partate a,inotran+ era+e ( !&)-to-p ate et ratioindex ( PB ) 'a+ een propo+ed a+ a +i,p e and nonin a+i e predi tor to e a ate 'epati i ro+i+ in +e era i er di+ea+e+

9).

&'e a++e++,ent predi tor+ o io ogi a i er n tion in de+i,p e ood para,eter+ + ' a+ !& and p ate et+ are ea+* to

+e and e+ti,ate. &'ere ore PB o d e a good a ternati ediagno+ti ,et'od to <i ro! an or i er iop+*

$). &'e p rpo+e

o t'i+ +t d* i+ to a idate t'e e i a * o PB or a++e++ing'epati i ro+i+ in 'i d'ood " ! a+ed on <i ro! an.

Materials and methods

1. PatientsCe e a ated t'e ini a and a orator* data o 23 pediatri

" ! patient+ (,a e/ e,a e 22/1) 8'o nder8ent <i ro! anat !e eran e ?'i drenD+ o+pita in !eo Korea et8een

ar ' 200$ and <e r ar* 2011. &'e diagno+i+ o( " !8a+ a+ed on: 1) a orator* radio ogi a or 'i+topat'o ogi

'ara teri+ti + o +teato'epatiti+ 2) no 'i+tor* o a o'oon+ ,ption and 3) no ot'er nder ine i er di+ea+e+

10).

2. Clinical, laboratory and radiological evaluationCeig't 'eig't and od* ,a++ index 8ere a ated.

E ood te+t re+ t+ 8ere o tained a ter o ernig't a+ting or ,ea+ re,ent o +er , !& a anine a,inotran+ era+e ( 7&)a ,in tota i ir in p ate et o nt prot'ro, in ti,einternationa nor,a i>ed ratio 'o e+tero trig * eride (&F)

g o+e o agen G '*a roni a id and !&/ 7& ratio( B). = tra+onograp'* (=!) and at ,agneti re+onan ei,aging ( B ) A anti i ation o t'e i er 8ere per or,ed.

3. APRIPB HI( !&/ pper i,it o nor,a )/p ate et o nt (10

9/7)

10011)

4. Liver stiffness measurement (LSM, FibroScan)&'e te 'ni a in+tr tion+ o <i ro+ an ( o+en+ Pari+

<ran e) 'a e een de+ ri ed in detai in o r pre io + report+12)

.Erie( * an tra+o nd tran+d er pro e 8it' an externadia,eter o 9 ,, i+ ,o nted on t'e axi+ o a i rator.Gi ration+ o o8 a,p it de and o8 reA en * (50 >) aretran+,itted * t'e tran+d er 8'i ' ind e an e a+ti +'ear 8a e t'at propagate+ t'ro g' t'e nder *ing ti++ e+. P +e-e 'o tra+o nd a A i+ition i+ +ed to o o8 t'e propagationo t'e +'ear 8a e and to ,ea+ re it+ e o it* 8'i ' i+ dire t *

re ated to ti++ e +ti ne++ (t'e e a+ti ,od + expre++ed a+/H3LG2 8'ere G i+ t'e +'ear e o it* and L i+ t'e ,a++ den+it*I on+tant or ti++ e+ ): t'e +ti er t'e ti++ e t'e a+ter t'e +'ear 8a e propagate+

13). &ran+ient e a+tograp'* ,ea+ re+ i er +ti -

ne++ et8een 25 ,, and 65 ,, e o8 t'e +kin + r a e in ao ,e t'at approxi,ate+ a * inder t'at i+ 1 , 8ide and 4, ong. &'i+ o ,e i+ at ea+t 100 ti,e+ arger t'an a iop+*

+a,p e and i+ t'ere ore ar ,ore repre+entati e o t'e 'epati paren '*,a

14). Ce ,ea+ red t'e i er +ti ne++ o t'e 'i dren

in o r +t d* a+ reported pre io + *6)

. n rie i er +ti ne++8a+ ,ea+ red A antitati e * on t'e rig't o e o i er t'ro g't'e inter o+ta +pa e+ 8it' t'e 'i d in t'e + pine po+ition

8it' ,axi,a a d tion o t'e rig't ar, nti 10 + e++,ea+ re,ent+ 8ere o tained. &'e ,edian a e o t'e 10 ,ea-+ re,ent+ o i er +ti ne++ 8a+ a ated a to,ati a * *+o t8are on a ,i ro o,p ter in+ta ed in t'e <i ro! an. &'e+ ore 8a+ expre++ed a+ t'e i er +ti ne++ + ore in ki opa+ a +(kPa). + e++ rate or ,ea+ re,ent o at ea+t 60M 'a+ een

on+idered re ia e14 15)

. o8e er in o r +t d* patient+ 8it' a+ e++ rate e++ t'an 90M 8ere ex ded ro, t'e ana *+e+ inan e ort to ,ake t'e data e en ,ore re ia e

6 16).

5. Liver biopsy7i er iop+* 8it' ore iop+* gadget (1$-F need e 150 ,,

engt'; Eiopin e ,edi !o ent na !8eden) 8a+ ond tedto o tain i er ti++ e+ * o r pre io + +t d*

12). !pe i,en+ on-

taining at ea+t 10 porta tra t+ and o at ea+t 15 ,, engt'8ere +ed and +t died * a pat'o ogi+t. Eiop+* +pe i,en+ 8ere

ixed in or,a in and e, edded in para in. <o r-,i ro,eter-t'i k +e tion+ 8ere +tained 8it' 'e,atox* in-eo+in-+a ran

a++on tri 'ro,e and Gi toria e. +pe i,en+ 8ere an-a *>ed t8i e * an experien ed i er pat'o ogi+t inded to

20 ttp://dx.doi.org/10.3345/kjp.2013.56.1.19

t'e ini a data. <o o8ing t'e ,et'od+ o "o i i et a .

5)

t'e,ain 'i+to ogi a eat re+ o,,on * de+ ri ed in " 7< /



" ! (+teato+i+ in a,,ation Iporta and o ar 'epato *te a ooning and i ro+i+) 8ere + ored a ording to t'e ! oring!*+te, or " <7 re ent * de e oped * t'e "ationa n+tit te+o ea t'-+pon+ored " ! ? ini a Be+ear ' "et8ork and,ean " <7 a ti it* + ore (" !) 8a+ a ated. &'e degreeo i ro+i+ 8a+ A anti ied on a 4-point + a e: 0 a +en e o

i ro+i+; 1 peri+in +oida or porta i ro+i+; 2 peri+in +oidaand porta /periporta i ro+i+; 3 +epta or ridging i ro+i+; 4

irr'o+i+. 7i er iop+* 8a+ per or,ed in 6 patient+.

6. Ethical clearance&'i+ +t d* 8a+ appro ed * t'e n+tit tiona Be ie8 Eoard

o on+ei =ni er+it* ?o ege o edi ine !e eran e o+pitaand arried o t in a ordan e 8it' t'e e +inki e aration(a+ re i+ed in din rg' 2000). n or,ed 8ritten on+ent 8a+o tained ro, a patient+ or appropriate + rrogate+ prior to+t d* enro ,ent.

Korean J Pediatr 2013;5 !1"#1$%25

7. Statistical analysisna *+i+ o t'e data 8a+ per or,ed 8it' P !C er. 1$.0

( E ?o. r,onk " =! ). =ni ariate ana *+i+ 8a+ on-d ted to e a ate t'e +igni(i an e o( gro p di((eren e+.7ogi+ti regre++ion ,ode + 8ere per or,ed or , ti ariateana *+i+ to identi * t'e ,o+t +igni i ant orre ation a,ongt'e aria e+. aria e+ in ni ariate ana *+e+ 8it' PN0.058ere introd ed into t'e , ti ariate ana *+i+. &'e diagno+ti per or,an e o t'e PB 8a+ a++e++ed +ing re ei er opera-ting 'ara teri+ti + (B ?) r e+. to a e+ are a++o-

iated 8it' t'e pro a i it* o a tr e po+iti e (+en+iti it*)and a tr e negati e (+pe i i it*). &'e B ? r e i+ a p ot o +en+iti it* er+ + 1-+pe i i it* or a po++i e to a e+.&'e ,o+t o,,on * +ed a ra * index i+ t'e area nder t'eB ? r e; a e+ near 1.0 indi ate 'ig' diagno+ti a ra *.B ? r e+ 8ere on+tr ted or deter,ination o 'epati

i ro+i+ in patient 8it' " <71#)

. =+ing B ? r e+ t'e

opti,a

to

a e

or

PB 8a+

'o+en

to

+'o8

a 95M

+en+i-ti it* or to o tain a 95M +pe i i it*. < rt'er,ore to opti,i>e

t'e diagno+ti per or,an e t'e + , o tr e po+iti e+ and tr enegati e+ o er t'e tota n , er o patient+ 8ere a ated to

Table 1. &ni'ariate analy(i( for factor( a((ociated )ith he*atic +,ro(i( in childhood nonalcoholic (teatohe*atiti(

Characteristic Total

Age(yr) 12.7±2.4 12.9±2.2 12.1±3.0 0.521

Male 22(96) 15(94) 7(100) 0.696Height(cm) 159.8±12.7 161.4±13.0 156.1±12.2 0.371Weight(kg) 70.2±15.5 72.8±14.9 64.3±16.1 0.233

Bodymassindex(kg/m2

) 27.3±3.32 27.5±2.84 26.7±4.46 0.079Cholesterol(mg/dL) 179.7±27.7 180.6±28.9 177.7±26.9 0.827Triglyceride(mg/dL) 136.8±60.6 157.3±56.6 85.5±35.9 0.011FBS(mg/dL) 93.2±10.5 94.2±12.6 91.0±3.1 0.521AST(IU/L) 80.9±69.2 98.8±76.5 40.0±10.8 0.049ALT(IU/L) 134.4±105.4 159.5±116.2 76.9±37.3 0.033Albumin(g/dL) 4.7±0.3 4.7±0.3 4.6±0.2 0.572T.bil(mg/dL) 0.5±0.1 0.5±0.1 0.5±0.2 0.851Plateletcount(10

3 /μL) 312.0±62.5 290.1±47.0 362.0±67.9 0.008

PTINR 0.96±0.04 0.96±0.03 0.98±0.06 0.281AAR 0.56±0.15 0.56±0.13 0.56±0.19 0.972APRI 0.82±0.77 1.04±0.83 0.33±0.08 0.015Hyaluronicacid(ng/dL) 15.8±5.0 15.4±6.1 16.8±3.2 0.582CollagenIV(ng/dL) 165.0±67.9 190.0±56.2 90.0±36.4 0.045fatMRIdualecho(%) 34.05±9.48 32.87±9.30 36.24±10.16 0.463fatMRItripleecho(%) 22.76±7.80 21.52±7.02 25.07±9.21 0.345Liverstiffness(kPa) 7.45±2.89 8.44±2.95 5.12±0.59 0.009FibroScansuccessrate(%) 99.1±1.9 98.8±2.2 100±0Valuesarepresentedasmean±standarddeviationornumber(%).FBS,fastingbloodsugar;AST,aspartateaminotransferase;ALT,alanineaminotransferase;T.bil,totalbilirubin;PTINR,prothrombintimeinternationalnormalizedratio;AAR,AST/ALTratio;APRI,ASTtoplateletratioindex;MRI,magneticresonanceimaging.

ttp://dx.doi.org/10.3345/kjp.2013.56.1.19 21


(n=23) -i,ro(i((stiffness>5.9kPa)(n=16) Non+,ro(i((stiffness ≤5.9kPa)(n=7) P value

! e n +

i t i :

i t *

Plateletcount(10/μL) 2.80(0.85–9.21) 0.051



,axi,i>e t'e + , o +en+iti it* and +pe i i it*.

Results

1. Factors associated with hepatic brosis tota o 23 'i d'ood " <7 patient+ 8ere in ded in

t'e in e+tigation. &'e ini a 'ara teri+ti + o a patient+are pre+ented in &a e 1. Ea+ed on re ent +t die+

#) t'e opti,a

to a e o 'epati i ro+i+ 8a+ +et a+ 5.9 kPa. !ixteen peop e 8ere in t'e i ro+i+ gro p 8it' i er +ti ne++ greater

Table2. ./lti'ariate analy(i( or actor( a((ociated )ith he*atic +,ro(i( inchildhood nonalcoholic (teatohe*atiti(

VariableHepatic

brosis

(stiffness>5.9

kPa)

OR(95% CI) P valueTriglyceride(mg/dL) 0.35(0.18–0.70) 0.243AST(IU/L) 2.97(1.27–6.93) 0.045ALT(IU/L) 0.69(0.30–1.58) 0.069

3

APRI 3.68(1.66–8.17) 0.035

CollagenIV(ng/dL) 0.96(0.362.54) 0.067OR,oddsratio;CI,condenceinterval;AST,aspartateaminotransferase;ALT,alanineaminotransferase;APRI,ASTtoplateletratioindex.

1.0

0.$

0.6

0.4

0.2

t'an 5.9 kPa and # peop e 8ere in t'e non i ro+i+ gro p 8it'+ti ne++ e++er t'an 5.9 kPa. &'ere 8a+ no gender di eren ein i er +ti ne++ a e+. &F !& 7& p ate et o nt PBand o agen G 'ad +igni(i ant +tati+ti a di((eren e+.

, ti ariate ana *+i+ 8a+ done +ing t'e aria e gi en *t'e ni ariate ana *+i+. !& and PB 8ere orre ated 8it''epati i ro+i+ (+ti ne++ greater t'an 5.9 kPa). &F 7& p ate et o nt and o agen G 'ad no re ation+'ip 8it' 'e- pati i ro+i+ (&a e 2).

2. Accuracy of APRI<ig. 1 +'o8+ a B ? r e ine repre+ented * PB a e+

o 'epati exi i it* and diagno+ti a ra * a o t 'epatii ro+i+ and irr'o+i+. &'e area+ nder B ? a e a ording

to PB 8a+ 0.$#5 8'i ' +'o8 'ig' diagno+ti a ra * ini er i ro+i+ and irr'o+i+. &o deter,ine t'e predi ting a i it*

o PB or 'epati i ro+i+ an opti,a to a e 8a+ +etand +en+iti it* +pe i i it* po+iti e predi ti e a e (PPG)

and negati e predi ti e a e ("PG) 8ere a ated (&a e 3).&'ree peop e (34.$M) 8ere in t'e gro p o PB O0.4669 and 15 peop e (65.2M) 8ere in t'e gro p 8it' PB 0.4669. &'e PB

a e o ,eaning i ro+i+ 8'en t'e to a e 8a+ +et at0.4669 pre+ented +en+iti it* o 94M +pe i i it* o 66M PPGo 94M and "PG o 64M.

3. Relations between hepatic brosis and biopsy result usingAPRI&a e 4 +'o8+ o,pared a e+ o PB o t'e 6 " <7

patient+ 8'o 8ere + je ted to i er iop+* te+t+. <or a 6 patient+ t'e <i ro! an a e+ 8ere o er $.1 kPa 8'i ' 8a+

a o e i ro+i+ +tage one and PB a e 8ere t'e +a,e or greater t'an 0.6531.

Discussion

0.00.0 0.2 0.4 0.6 0.$ 1.0

er t'e pa+t e8 de ade+ t'e pre a en e and in iden e o o e+it* in 'i dren 'a e in rea+ed +igni i ant *. ong 8it'

1-!pe i(i it*

Fig. 1. Recei'er o*eratin characteri(tic( !R " c/r'e for

a(*artate

a3inotran( era(e to *latelet ratio inde45 6he area /nder the R12 c/r'e()a( 0 785 for the deter ination of he*atic +,ro(i( !(ti9ne((:5$ Pa"

t'i+ in rea+e " <7 'a+ e o,e t'e ,o+t o,,on a +eo 'roni i er di+ea+e in 'i dren. en t'o g' t'e nat ra'i+tor* o 'i d'ood " <7 i+ n ertain it i+ + gge+tedt'at +i,p e +teato+i+ 'a+ a enign progno+i+ 8'i e " !

Table3. Acc/racy o APRI c/to9 'al/e( in *redictin0 (i0ni+cant he*atic +,ro(i( and cirrho(i(

APRI Total(n=23)FibroScan

Stiffness ≤5.9kPa Stiffness>5.9kPaSensitivity Specicity PPV NPV

≤0.4669 8(34.8) 6(85.7) 2(12.5) 94 66 94 64>0.4669 15(65.2) 1(14.3) 14(87.5)Valuesarepresentedasnumber(%).APRI,aspartateaminotransferasetoplateletratioindex;PPV,positivepredictivevalue;NPV,negativepredictivevalue.

22 ttp://dx.doi.org/10.3345/kjp.2013.56.1.19



Table 4. -indin0( Related to A((e((3ent .ethod( o He*atic -i,

ro(i( in <i'er =io*(y a(e(

CaseAge(yr) SexAST/ALT

1 13 M 225/372 2 18.7 2.1986

2 12 M 238/480 2 15.7 1.82883 10 M 131/326 2 11.8 1.34254 12 F 72/146 2 8.1 0.83715 11 M 90/140 2 8.2 0.76066 15 M 74/156 1 8.1 0.6531AST,aspartateaminotransferase;ALT,alanineaminotransferase;APRI,ASTtoplateletratioindex;Fibrosisstage,brosisstageusingliverbiopsy.

and i ro+i+ an de e op into r*ptogeni irr'o+i+ and

'epato e ar ar ino,a1 2)

. &'ere(ore ear * identi(i ationo i er i ro+i+ in " <7 an aid in progno+i+ and in de-ter,ining a t'erape ti p an and it an pre ent rt'er de-

e op,ent o i er di+ea+e1# 1$). a ation o t'e progre++iono( di+ea+e in " <7 patient+ depend+ on +ero ogi te+t+=! o,p ted to,ograp'* B and ot'er radioa ti e te+t,et'od+. o8e er i ro+i+ progre++ion e+pe ia * in t'e ear *+tage i+ 'ard to predi t and i+ o ten ina rate.

=nti no8 i er iop+* 'a+ een t'e e+t option or e a -ating i er i ro+i+. t i+ t'e e+t and ,o+t o je ti e ,et'odo te+ting t it i+ a +o an in a+i e ,et'od 8'i ' an ringa o t a pain and o,p i ation+ e+pe ia * in 'i dren. &'ere-

ore t'i+ ,et'od annot e app ied to a 'i dren. +o i eno g' ti++ e i+ not pro ided 'epati paren '*,a annot

a e repre+ented. n addition a patientD+ n8i ingne++ totake t'e ,edi ation and t'e inan ia pre++ re ,ake t'i+,et'od 'a enging or repetiti e ,edi ation and rt'er in e+tigation o t'e patientD+ ondition

1# 1$). ; ording *

re+ear ' to ind a nonin a+i e and a rate ,et'od 'a+ eenin rea+ing and ne8 te 'niA e+ are no8 eing in ented

19 20).

=n ort nate * ,o+t o t'e ne8er ,et'od+ are expen+i e or are o,p i ated and are t'ere ore not appropriate or on-

enient (or o,,on +age 21 22)

. +o 'roni 'epatiti+ ?(? ?) patient+ 8ere +ed in t'e+e in e+tigation+ and it i+

n ertain t'at t'e* an e +ed 'i d'ood " <7 patient+.&'e re ent * de e oped <i ro! an i+ a nonin a+i e ,et'od to

,ea+ re t'e i er +ti ne++14 23)

. <i ro! an 'a+ +o,e po+iti eA a itie+ in ding a pain e++ pro ed re rapid te+t ti,e ( e++t'an 5 ,in te+) and +i,p e per or,an e. t a +o o er+ ande a ate+ a arger part o t'e i er and i+ +en+iti e o,paredto t'e +ero ogi a ,arker+

2). 7! and i ro+i+ +tage in " <7

patient+ 'a e a +igni i ant orre ation a+ on ir,ed * i er iop+* re+ t+

#). +o 7! i+ ea+i e and re ated to i er

i ro+i+ in 'i dren 8it' 'roni i er di+ea+e+6)

. &'ere ore7! i+ a nonin a+i e and +e ,oda it* or identi *ingt'e +e erit* o 'epati i ro+i+ in 'i d'ood " ! patient+

#).


<i ro! an deter,ine+ t'e degree o i er i ro+i+ 8it' 'ig'a ra *. o8e er t'e eA ip,ent i+ expen+i e and not pra ti a or ro tine te+ting in ,o+t ini a nit 8or d8ide

24).

7i er ti++ e in e+tigation 8o d e , ' ,ore on enient andinan ia * + pporta e i a ne8 and +i,p e +ero ogi i er i ro+i+ ,et'od 8ere de e oped to rep a e i er iop+* and

<i ro! an. n idea +ero ogi i ro+i+ index 8'i ' o d app *and at*pi a organ + ' a+ i er , +t 'a e good repeata i it*and o8 o+t. Be ent * +e era +t die+ 'a e atte,pted to +e+ero ogi te+t+ to predi t i er i ro+i+ and irr'o+i+

25). o+t

'i d'ood " ! patient+ t'at are a+*,pto,ati and 'a e a,i d degree o e e ated i er en>*,e + ' a+ !& and 7&are o o8ed p 8it'o t an* noti i ation+ o t'e +igni i ant'epati i ro+i+ in ,edi a pra ti e. &'ere ore it i+ i,portantto introd e +i,p e and predi ti e +ero ogi a ,arker+ o 'epati i ro+i+ t'at an e +ed in 'i dren 8it' " ! at an*ti,e.

n t'i+ +t d* <i ro! an 8a+ +ed to ,ea+ re i er +ti ne++and to o er o,e t'e di i t* i,itation+ and o,p i ation+o i er iop+* in 'i dren a+ a a+e ine +t d* o 'epati i ro+i+.&'e +i,p e and rea i+ti ,et'od o PB a+ a pro,i+ing pre-di tor 8a+ e a ated or +e ne++ in ,ea+ ring i er i ro-+i+

$ 26 2#). =nti no8 ,an* in e+tigation+ 'a e atte,pted to

predi t i er i ro+i+ and irr'o+i+ t'ro g' +er , ,arker+.o8e er it i+ i,ited d e to o,p ex ,at' eA ation+

10). ?o,-

pared to t'i+ PB i+ a+ed on t8o ro tine a orator* te+t+and i+ t'ere ore a pro,i+ing too 8it' i,ited expen+e and8ide+pread a ai a i it*

$). PB 'a+ een +ed in t'e e a ation

o patient+ 8it' a o'o i i er i ro+i+ ? E and ? ? 8it''ig' a ra ie+9). t'o g' t'e +t d* 8a+ per or,ed or ? ?t'e 'ig' diagno+ti po8er o PB or predi ting +igni i ant

i ro+i+ 'a+ een reported2$)

. +o re ati e * 'ig' a ra * o PB or predi ting +igni i ant i ro+i+ 'a+ een de,on+trated

e en in 'i dren 8it' ? E29 30)

. o8e er t'ere are e8 report+ +ing PB a+ a nonin a+i e and +e ,et'od or t'eidenti i ation o 'epati i ro+i+ and irr'o+i+ in 'i d'ood " <7 . r +t d* deter,ined t'e +e ne++ and re ia i it* o t'e PB in a++e++ing i ro+i+ in 'i dren 8it' " <7 . onedaet a .

#) +ed <i ro! an and +et t'e i er +ti ne++ to a e

(kPa) to 5.9. &'e* predi ted +en+iti it* o $6.1M +pe i i it* o

$6.1M PPG o 9#.1M and "PG o 59.3M (8'i ' 8a+ rea+ona *i,portant). n t'i+ +t d* data ro, a pre io + in e+tigation8a+ +ed and <i ro! an 8a+ +ed to ,ea+ re t'e i er exi- i it* o " <7 patient. &'en +ero ogi te+t+ 8ere done todeter,ine t'e orre ation et8een !& and PB . Ea+ed ont'e a o e to a e o 5.9 8'en i ro+i+ (Q<1) 8a+ predi tedit 8a+ +'o8n t'at PB 'ad po+iti e orre ation Iodd+ ratio3.6$; 95M on iden e inter a 1.66 to $.1#; PH0.035 8it' 'e- pati i ro+i+ (+ti ne++ 5.9kPa). ?o,,on * e a +e o t'e pro e,+ and i,it+ o i er iop+ie+ in predi ting i er i ro+i+

ttp://dx.doi.org/10.3345/kjp.2013.56.1.19 23

(IU/L) Fibrosis stage

FibroScan(kPa) APRI




it i+ e e ti e to +e nonin a+i e +ero ogi ,arker+ 8'en areander t'e B ? ( =B ?) a e+ are o er 0.$0

1#). =B ? a e+ o

PB a +o on+idera * and a rate * diagno+ed i er i ro+i+to t'o+e o 0.$#5. &'i+ on e*ed + periorit* in diagno+ti

+e( ne++. &'i+ did not di((er +igni(i ant * (ro, =B ?a e+ targeted to ? ? patient+: 0.$0 0.$1

25 31). &'i+ re+ t

+ pported t'e a idne++ o t'e re ent +t d*. n ot'er +t die+PB 'a+ 'ig' re ation+'ip 8it' i er i ro+i+9 26) and one re-

ported 'ig' diagno+ti a ra * ( =B ? 0.$$ I< 2 ) 0.94I<H4 )

2$). o,e+ti a * PB 'ad a etter re+ t a+ a +ero ogi

te+t indi ating i er i ro+i+ t'an B or ? E patient+32)

.n t'i+ +t d* PB predi ta i it* o i ro+i+ a+ed on PB

to(( a e o( 0.4669 8ere e+ti,ated a ording to B ?r e re+ t+. + a re+ t 'ig' predi ted + ore+ (+en+iti it*

o 94M +pe i i it* o 66M PPG o 94M and "PG o 64M)'a e +'o8n t'at it o d e +ed or predi ting i er i ro+i+.C'en 6 " <7 patient+ 8'o 'a e a read* done i er iop+*8ere te+ted 8it' <i ro! an and ;PB a e+ indi id a

<i ro! an a e+ 8ere t'e +a,e or greater t'an $.1 kPa PBa e+ 8ere t'e +a,e or greater t'an 0.6531 and a t'e patient+

8ere a o e i ro+i+ +tage 1. C'en an PB to o 0.46698a+ app ied it 8a+ app i a e in inding o t t'e exi+ten eo i ro+i+. &'ere ore PB an e +ed to A i k * predi t

i er i ro+i+ 8'en i er iop+* i+ i,po++i e to per or, or inapp i a e. t'o g' t'ere are +e era i,itation+ in dingt'e +,a n , er o patient+ and t'e +'ort o o8- p PB+'o8+ a po++i i it* a+ a nonin a+i e ,et'od to a++e++ 'epati

i ro+i+ progre++ion. r re+ t+ +'o8ed t'at PB + ore+ or-re ate +igni i ant * to i ro+i+ in patient+ 8it' " <7 . n t'e

t re i o je t patient+ in rea+e and o o++a o'ort +t d*

operate and diagno+ti a ra * on i er (i ro+i+ i+ rai+ed * o, ining +ero ogi te+t and <i ro! an PB o d e a

+e ,et'od or predi ting i er i ro+i+ in t'e ear * +tage,onitoring t'e pro e++ ontin o + * and deter,ining a t'erape ti re.

n on +ion t'i+ +t d* de,on+trated t'at PB o d ean ea+* nonin a+i e +i,p e and readi * a ai a e ,et'od

or t'e predi tion o +igni i ant 'epati i ro+i+ in 'i d'ood " <7 . <o o8- p e a ation or 'epati i ro+i+ +'o d e per or,ed * a pediatri 'epato ogi+t.

References

1. Ear+'op "J <ran i+ ?! ! '8i,,er JE 7a ine J . "ona o'o iatt* i er di+ea+e a+ a o,or idit* o 'i d'ood o e+it*. Pedea t' 2009;3:2#1-$1.

2. <ier intean -Erati e i i ? ina Petri+or &ri + 7 "egrean7 ?ar+toi ?. "onin a+i e in e+tigation+ or non a o'o i

att* i er di+ea+e and i er i ro+i+. Cor d J Fa+troentero2010;16:4#$4-91.

3. "o i i G i+i Gania &iri e i ? Pietro atti+ta Eedogni F.&'e pediatri " <7 i ro+i+ index: a predi tor o i er i ro+i+in 'i dren 8it' non-a o'o i att* i er di+ea+e. E ? ed2009;#:21.

4. P'er+on ! !te8art !< ender+on / E rt a* ?P. !i,p enon-in a+i e i ro+i+ + oring +*+te,+ an re ia * ex dead an ed i ro+i+ in patient+ 8it' non-a o'o i att* i er di+ea+e. F t 2010;59:1265-9.

5. "o i i G Bea e i+i orino F &renta Pi+ani et a ./ e ated +er , 7& in 'i dren pre+enting to t'e e,ergen * nit:re ation+'ip 8it' " <7 . ig 7i er i+ 2009;41:#49-52.

6. de 7eding'en G 7e Eai E Be o i++o x 7 <o rnier ? <o 'er J iette G et a . 7i er +ti ne++ ,ea+ re,ent in 'i dren +ing<i ro! an: (ea+i i it* +t d* and o,pari+on 8it' <i rote+ta+partate tran+a,ina+e to p ate et+ ratio index and i er iop+*. JPediatr Fa+troentero " tr 200#;45:443-50.

#. oneda oneda a8atari < jita K /ndo ida eta . "onin a+i e a++e++,ent o i er i ro+i+ * ,ea+ re,ent o +ti ne++ in patient+ 8it' nona o'o i att* i er di+ea+e (" <7 ).

ig 7i er i+ 200$;40:3#1-$.$. 7oae>a-de -?a+ti o ; Pa>-Pineda < iedo-?ardena+

!an 'e>- i a < Garga+-Gora ko a <. !& to p ate et ratio index( PB ) or t'e nonin a+i e e a ation o i er i ro+i+. nn

epato 200$;#:350-#.9. 7in ?! ?'ang ?! ang !! e' R 7in ?C. Betro+pe ti e

e a ation o +er , ,arker+ PB and !&/ 7& or a++e++ingi er i ro+i+ and irr'o+i+ in 'roni 'epatiti+ E and ? patient+

8it' 'epato e ar ar ino,a. ntern ed 200$;4#:569-#5.10. < jii /no,oto < k +'i,a C ' ji ! ori Ko a*a+'i

! et a . "onin a+i e a orator* te+t+ propo+ed or predi tingirr'o+i+ in patient+ 8it' 'roni 'epatiti+ ? are a +o +e in

patient+ 8it' non-a o'o i +teato'epatiti+. J Fa+troentero2009;44:60$-14.

11. Pa ,eri 7 Cang Bo >e "? de ,a ek < F * ?o+er E et a . "onin a+i e e a ation o 'epati i ro+i+ +ing

a o +ti radiation or e- a+ed +'ear +ti ne++ in patient+ 8it'nona o'o i att* i er di+ea+e. J epato 2011;55:666-#2.

12. ?'ang K Park J Ko' Ki, ! ?' ng K! ' J& et a .epati i ro+i+ + an or i er +ti ne++ + ore ,ea+ re,ent: a+e preendo+ opi + reening te+t or t'e dete tion o ari e+ in

po+toperati e patient+ 8it' i iar* atre+ia. J Pediatr Fa+troentero " tr 2009;49:323-$.

13. ?a+tera 7 <orn+ S erti . "on-in a+i e e a ation o i er i ro+i+ +ing tran+ient e a+tograp'*. J epato 200$;4$:$35-4#.

14. ?a+tera 7 Gergnio J <o 'er J 7e Eai E ?'ante o p / aa+er et a . Pro+pe ti e o,pari+on o( tran+ient e a+tograp'*

<i rote+t PB and i er iop+* or t'e a++e++,ent o i ro+i+ in'roni 'epatiti+ ?. Fa+troentero og* 2005;12$:343-50.

15. Gi>> tti < rena = Bo,ane i BF Bega 7 <o+ 'i ?o agrande! et a . 7i er +ti((ne++ ,ea+ re,ent predi t+ +e ere porta'*perten+ion in patient+ 8it' ?G-re ated irr'o+i+. epato og*200#;45:1290-#.

16. "g *en-K'a / ?'ate ain &ra,ier E e ro, e A e ? Bo ertE Jo * JP et a . ++e++,ent o a+*,pto,ati i er i ro+i+ ina o'o i patient+ +ing i ro+ an: pro+pe ti e o,pari+on 8it'+e en non-in a+i e a orator* te+t+. i,ent P'ar,a o &'er 200$;2$:11$$-9$.

1#. Ki, ! !eok J an !J Ko' . ++e++,ent o i er i ro+i+ andirr'o+i+ * a+partate a,inotran+ era+e-to-p ate et ratio index

in 'i dren 8it' i iar* atre+ia. J Pediatr Fa+troentero " tr 2010;51:19$-202.

1$. Kaneda a+'i,oto at+ ji ! &ok +'ige K !'iratori K.

24 ttp://dx.doi.org/10.3345/kjp.2013.56.1.19

*a roni a id e e + an predi t +e ere i ro+i+ and p ate eto nt+ an predi t irr'o+i+ in patient+ 8it' nona o'o i att*



i er di+ea+e. J Fa+troentero epato 2006;21:1459-65.19. *er+ BP Bat>i G , ert-Ei+, t < ?'ar otte < Po*nard &;

=7& G B? Fro p. Fro pe dT t de tidi+ ip inaire + r e+Pat'o ogie+ 7iUe+ a Gir + ?. Eio 'e,i a ,arker+ o i er i ro+i+:a o,pari+on 8it' 'i+tori a eat re+ in patient+ 8it' 'roni'epatiti+ ?. , J Fa+troentero 2002;9#:2419-25.

20. , ert-Ei+, t < Bat>i G Pieroni 7 ?'ar otte < Een'a,o Po*nard & et a . Eio 'e,i a ,arker+ o i er i ro+i+ in patient+8it' 'epatiti+ ? ir + in e tion: a pro+pe ti e +t d*. 7an et 2001;35#:1069-#5.

21. d'a " " ne+ . a ation o i er i ro+i+: a on i+ere ie8. , J Fa+troentero 2004;99:1160-#4.

22. Po*nard & , ert-Ei+, t < ntean e++o + *er+ BP&'a t et a . er ie8 o t'e diagno+ti a e o io 'e,i a,arker+ o i er i ro+i+ (<i ro&e+t ?G <i ro! re) and ne ro+i+( ti&e+t) in patient+ 8it' 'roni 'epatiti+ ?. ?o,p epato2004;3:$.

23. !'a'een Can < *er+ BP. <i ro&e+t and <i ro! an or t'e predi tion o 'epatiti+ ?-re ated i ro+i+: a +*+te,ati re ie8 o diagno+ti te+t a ra *. , J Fa+troentero 200#;102:25$9-600.

24. R'o K Fao ?< R'ao P 7i 7 R'eng B Sian J? et a .!i,p er + ore o ro tine a orator* te+t+ predi t+ i er i ro+i+in patient+ 8it' 'roni 'epatiti+ E. J Fa+troentero epato2010;25:1569-##.


25. 7ero* G i eret " !t r, " &ro ,e ? Ben er+e> J? <a reP et a . Pro+pe ti e o,pari+on o +ix non-in a+i e + ore+ or t'e diagno+i+ o i er i ro+i+ in 'roni 'epatiti+ ?. J epato200#;46:##5-$2.

26. !'in CF Park ! Jang K a'n & Ki, JE 7ee ! et a .+partate a,inotran+ era+e to p ate et ratio index ( PB ) an

predi t i er i ro+i+ in 'roni 'epatiti+ E. ig 7i er i+ 200$;

40:26#-#4.2#. Eor+oi Giana ! &akei K ?o ari e a,ag ti ? F > E !tra ++/. =+e o !& p ate et ratio index ( PB ! ore) a+ an a ternati eto i er iop+* or treat,ent indi ation in 'roni 'epatiti+ ?.

nn epato 2009;$:26-31.2$. Cai ?& Freen+on JK <ontana BJ Ka ei+ ' J arrero J

?onjee ara, ! et a . +i,p e nonin a+i e index an predi t ot' +igni i ant i ro+i+ and irr'o+i+ in patient+ 8it' 'roni'epatiti+ ?. epato og* 2003;3$:51$-26.

29. Cai ?& ?'eng ?7 Cee an ?'an / ?' a C et a . "on-in a+i e ,ode + or predi ting 'i+to og* in patient+ 8it' 'roni'epatiti+ E. 7i er nt 2006;26:666-#2.

30. 7e en+>tejn !ki a !o anie -7oto8+ka Ka >,ar+ki. ; +i,p e nonin a+i e index (;PB ) predi t+ ad an edi er i ro+i+ in 'i dren 8it' 'roni 'epatiti+ E. epato og*

2005;41:1434-5.31. 7a kner ? !tr er F 7ieg E 7ei ! ner P Eank ti ? et

a . ?o,pari+on and a idation o +i,p e nonin a+i e te+t+or predi tion o i ro+i+ in 'roni 'epatiti+ ?. epato og*

2005;41:13#6-$2.32. !i, !J ?'eong J ?'o !C Ki, J! 7i, & !'in et a .

/ i a * o !& to p ate et ratio index in predi ting +e ere 'epati(i ro+i+ and irr'o+i+ in 'roni 'epatiti+ E ir + in(e tion.Korean J Fa+troentero 2005;45:340-#.

ttp://dx.doi.org/10.3345/kjp.2013.56.1.19 25

the efficacy of aspartate aminotransferase-to-(1)

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