jurnal kolestasis 1

7/21/2019 jurnal kolestasis 1

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Original Article

Diagnostic Evaluation Of Cholestasis In

Infants And Young Children In

AlexandriaA Abdel Moniem Deghady, M Abdel-Fattah, M Abdel-Kader, M Naguib, E Madina, M Abd El Gawad

Keywords

atresia, cholestasis, hepatitisCitation

A Abdel Moniem Deghady, M Abdel-Fattah, M Abdel-Kader, M Naguib, E Madina, M Abd El

Gawad.Diagnostic Evaluation O !holestasis "n "nants And #oung !hildren "n Ale$andria. he

!nternet "ournal o# $ediatrics and Neonatology. %&&' (olume ) Number *.Abstract

+holestasis includes retention o# conugated bilirubin, bile salts and other components o# thebile. !t is not a disease rather, it is a symptom o# many diseases. his study aimed at #inding out

the etiological diagnosis o# chronic cholestatic lier diseases among cases o# cholestasis admitted

to El-/hatby +hildren 0ospital-1niersity o# Ale2andria, Egypt during a % years period./eenty in#ants and children with their ages ranging #rom * to 3) months were included in the

study. (arious diagnostic modalities were used to establish their diagnosis.

$atients were diagnosed as neonatal hepatitis 4n5%6, 7*.789, biliary atresia 4n5*:, %7.389, and amiscellaneous group 4n5%7, 37.389.

he conclusion is that in Ale2andria neonatal hepatitis is the commonest cause o# in#antile

cholestasis and biliary atresia is the second common cause.

Introduction

+holestasis includes retention o# conugated bilirubin, bile salts and other components o# the

bile. !t is not a disease rather, it is a symptom o# many diseases there#ore, it is a signal that

disease e2ists. he mechanisms by which diseases produce cholestasis can be classi#ied as eitherhepatocellular or obstructie cholestasis. 4*9

he #irst diagnostic concern o# cholestatic disorders should be the di##erentiation o#

hepatocellular #rom obstructie cholestasis, because it represents the di##erentiation betweenmedical ersus surgical disorders. All disorders that desere interention in the #irst #ew months

o# li#e are obstructie disorders, and their timely identi#ication can improe outcome.4%9

;ecause o# the #re


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Patients and Methods

/eenty patients 43) #emales and 37 males9 with their ages ranging #rom * to 3) months wereenrolled in the study hey were #ul#illing the clinical and laboratory criteria o# chronic

cholestasis, that is cholestasis persisting beyond two wee=s o# age in neonates, cholestasis which

is e2pected to persist in in#ants, or cholestasis lasting #or #our wee=s or more in children. 4 79 An

in#ormed consent was ta=en #rom the parents o# all patients included in the study. $atients withthe classical clinical picture o# acute hepatitis and those with cholestasis showing signs o# end

stage lier #ailure were e2cluded #rom the study.

Eery patient was subected to a #ull history ta=ing stressing on the age , se2, birth weight ,onsetand duration o# aundice, colour o# urine and stool as well as serological eidence o# maternal

in#ectious diseases . Also eery patient was subected to thorough clinical e2amination,

laboratory inestigations including total and direct serum bilirubin, serum bile salts 4'9, thecholestatic en>ymes al=aline phosphatase 4A?$9 and gamma glutamyle transpeptidase 4GG9

4),:9, aspartate transaminase 4A/9, alanine transaminase 4A?9, prothrombin time and actiity,

serum albumin, #asting blood glucose ,urine e2amination #or bilirubin,bile salts and reducing

substances.

/erological tests #or hepatitis ; sur#ace antigen, hepatitis + irus !gG antibodies , o2oplasma,@ubella, +ytomegaloirus 4+M(9 and herpes irus40/(9 i,e@+0 !gM antibodies were done

using E?!/A techni


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Figure 2

Figure * he 3 maor groups o# cholestatic patients in the study

Among the clinical parameters used in this study only birth weight, age o# onset o# aundice and

presence o# splenomegaly were #ound to be use#ul. !n#ants with neonatal hepatitis were #ound to

hae low birth weight and later onset o# aundice than those haing biliary atresia table 4!9.Moreoer splenomegaly was #ound in higher percentage in in#ants with neonatal hepatitis

compared to biliary atresia cases able 4! 9 Anthropometric data and onset o# aundice.


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Figure 3

able % +linical #indings in the studied groups

All cases had eleated serum leels o# total bilirubin 4*&.B3.)mgdl9 with eleated direct#raction 46.7 3.7 mgdl9.!n )' in#ants, eleated leels o# serum transaminases 4re#erence alue is up to 7& u?9were

#ound, o# those : patients had mar=edly eleated leel 4%&& u?9,'B had moderate eleation

between :& and %&& 1?. he remaining ' patients had normal transaminases leel./erum al=aline phosphatase leel 4re#erence alue 3-*3 KHA9was high in all in#ants with a mean

o# 6&3& =HA. Gamma glutamyl transpeptidase leel was normal in 3 in#ants 4*&-7& 1?9, low

in % 4I*& 1?9 and high in )' in#ants 4 7& 1?9. !n those with eleated leels, *B had GGgreater than #ie #old eleation 4%&& 1?9 and 7: had GG less than #ie #old eleation 4I %&&

1?9.

!n patients who had normal and low GG 4' cases9,7 had eleated serum bile salts leel, while

the 'thhad normal serum bile salts 4I 6.B Cmol?9 as well as normal GG, A?$, A/ and A?leels.

!mpaired synthetic lier #unction 4re#lected by serum albumin and prothrombin actiity9 were

detected in the maority o# cases. Fasting blood glucose leel was normal in all cases e2cept twowho had hypoglyceamia.

1rine tests #or conugated bilirubin and bile salts were done #or all cases and reealed positie

results. n the other hand ,urine samples were negatie #or reducing substances .;y abdominal ultrasound e2mination , two patients were proed

to hae choledochal cysts.

able 4!!! 9 show the etiological diagnosis o# neonatal hepatitis cases, while table 4!(9 show the#inal diagnosis o# all cholestatic patients included in the study .

Figure 4

able 3 Etiology o# neonatal hepatitis in group *


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Figure 5

able 7 Final diagnosis o# all studied cases

+ytomegaloirus was the commonest congenital in#ection reported. !t constituted '%.%8 o#

in#ants with congenital in#ection while herpes simple2 irus constituted *38 , and combinedin#ection o# both occurred in %).*8 while congenital to2oplasmosis constituted B.:8 o#

congenital in#ectious agents.he miscellaneous group included %% 43*.789 patients who were diagnosed as Neimann-$ic=

disease 4*.7389, Glycogen storage disease4%.B)89 JFigure %, +ongenital hepatic

#ibrosis4*.7389, tyrosinemia 4*.7389, alpha-*- antitrypsin de#iciency 4*.7389,recurrent benign

intrahepatic cholestasis 4*.7389 ,;ylerLs disease47.%689 JFigure 3, non syndromic intrahepaticbile duct paucity4'.:*89, ;iliary cirrhosis4'.:*89 ,and !diopathic J with e


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e compared di##erent diagnostic modalities in the diagnosis o# neonatal hepatitis and biliary

atresia.4able (H(! 9.Figure 8

able ' Diagnostic per#ormance o# the (arious diagnostic tools regarding neonatal hepatitis

Figure 9

able ) Diagnostic per#ormance o# the arious diagnostic tools regarding biliary atresia


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he clinical tool was more speci#ic in diagnosing biliary atresia than in diagnosing neonatal

hepatitis 4B).B8 ersus %6.389, also more accurate 4B*.78 ersus '&89 but less sensitie4)7.:8

ersus :6.389.ransamiases were speci#ic in di##erentiating biliary atresia #rom neonatal hepatitis or other

causes o# cholestasis 4B'.78 ersus 3).*89, also more accurate 4B&8 ersus ':89 but less

sensitie 4)78 ersus B%.B89. /erum GG leel is the only biochemical test #ound to be o#discriminating alue. GG alues less than %&& 1? correlated with the diagnosis o#

hepatocellular cholestasis while GG alues more than %&& 1? #aored the diagnosis o# biliary

atresia 4table (!!9. 0oweer, low or normal GG leel was #ound in patients with ;ylerLs diseaseand benign recurrent intrahepatic cholestasis

Figure 10

able (!! he alue o# GG leels in di##erentiating the cholestatic groups

/erologic tests were speci#ic #or congenital in#ection. they should be done with histopathological

diagnosis o# neonatal hepatitis to con#irm diagnosis. !n this study the presence o# +M(- !gM in

the serum o# cholestatic in#ants didnLt e2clude biliary atresia .

Abdominal ultrasonography is an e2cellent test in e2cluding choledochal cyst as a cause o#in#antile cholestasis. !n this study abdominal ultrasound was #ound to be more speci#ic #or the

diagnosis o# biliary atresia 4B).%8 ersus 3&.689 and more accurate 4B%.38 ersus '%.689 but

less speci#ic 4)7.:88 ersus B%.B89. n the other hand hepatobiliary scintigraphy is a sensitiebut less speci#ic test in di##erentiating biliary atresia #rom intrahepatic cholestasis.

Discussion

+holestasis deelops in response to a wide ariety o# causes. !rrespectie o# the etiology, itspathophysiological conse


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Dan=s et al4*6::9 4*'9 and Dic= et al4*6B'9, 4*39 suggested idiopathic hepatitis as the main cause

o# neonatal hepatitis, but their studies antedate the descriptions o# recently recogni>ed metabolic

causes o# cholestasis. n the other hand adances in preentie medicine may result in the lowerincidence o# congenital in#ections compared to idiopathic hepatitis in some recent studies. 4*)9

;iliary atresia was the second common cause o# cholestasis in the present study 4%78 o# cases9,

this agrees with studies made by Dic= et al 4*39 %&.78 ,while Dan=s et al 4*'9 #ound e2trahepaticbiliary atresia in 3%.%8 o# cholestatic cases .wo recent !ndian studies 4**,*:9 reported biliary

atresia in 378 and *6.78 in in#ants with cholestatic syndrome respectiely. Early diagnosis and

surgical correction is o# at most bene#it #or such patients.he low incidence o# choledochal cyst in the present study 4%.689 coincides with reports o#

0oward et al 4*)9, and achha et al 4*:9 38 and 78 respectiely o# their cholestatic cases.

Metabolic lier diseases in the #orm o# tyrosinemia, O* anti-trypsin de#iciency, Niemann $ic=

disease, congenital hepatic #ibrosis and glycogen storage disease were diagnosed in B.':8 o# ourcholestatic cases. /eeral reports o# ariable incidence and types o# metabolic lier diseases in

cases o# cholestasis are present. An !ndian study 4*B9 reported it to cause *3.B8 o# cases in the

#orm o# tyrosinemia, O* anti-trypsin de#iciency, hereditary #ructose intolerance and

hemochromatosis. achha4*69,reported 78 o# cases while 0oward et al 4*)9 diagnosed O* anti-trypsin de#iciency in *:.78 o# cases with in#antile cholestasis. ther studies conducted in

?ondon4*39,slo4%&9 and Australia4*'9 reported O* anti-trypsin de#iciency as an etiological cause in*38,).'8 and 7.:8 o# cases with in#antile cholestasis respectiely. he ariable incidence o#

metabolic lier diseases reported in di##erent studies may be attributed to underlying genetic

#actors.;ylerLs syndrome has a world wide distribution and occurs most commonly in societies with high

rate o# consanguinity. wo out o# three patients with ;ylerLs disease in this study had

consanguinity between their parents. 0igh incidence o# the disease was reported in the 1nited

/tates among descendants o# "acob ;yler 4Amish community9 4%*9. !n !ndia, achha4*:9 reportedrelatiely low incidence o# ;ylerLs disease among in#ants with cholestasis P B.38 Q.

he incidence o# non-syndromic bile duct paucity in this study was %.B8 while the syndromic

bile duct paucity 4AlagilleLs syndrome9 was not #ound. hese #indings agree with the results o#the "ohnLs study 4**9 but others reported higher incidence o# AllagilleLs syndrome 4*',

%%9 might be

due to di##erent genetic bac=ground.

Conclusion

From the present study we can conclude that

Neonatal hepatitis is the commonest cause o# in#antile cholestasis and biliary atresia is the

second common cause.@outine laboratory tests as well as tests #or speci#ic hepatic disorders are important #or the

diagnosis and ealuation o# cholestasis in pediatric age.

0istological study is a aluable tool in etiological diagnosis o# cholestasis proided that it is

done by an e2pert hands and lead to no complications.Metabolic lier diseases are clinically e2cellent simulators to the common pediatric illnesses and

should be considered and searched #or during the wor= up o# cholestatic disease diagnosis in

pediatrics.

Correspondence to

$ro#. A=ram Deghady , +linical pathology Dept, Faculty o# Medicine , 1niersity o# Ale2andria,

+hamplion street,A>arita, Ale2andria, Egypt . E-mail a=ram)*Ryahoo.com

References


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*. hitington $F. +hronic +holestasis o# !n#ancy. $ediatr +linic North Am *66) 73 4*9 *-%)

%. @omer> @, /o=ol @". Medical management o# cholestasis. !n ?ier disease in children.

Mosby /t ?ouis, *667 3')-B%3. Fit>gerald "F. +holestatic disorders in in#ancy. $ediatr +lin North America *6BB 3'4%9 3':-

:3

7. ;alistreri F. +holestasis. !n ;ehrman @E, Kliegman @M, Arin AM, eds. Nelson e2tboo=o# pediatrics, *)th ed. $hiladelphia ; /aunders +ompany, %&&& **33-'.

'. /treet "M,ra##ord D"0,Ma=in 0?".he

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jurnal kolestasis 1