Etiology and Complication of Liver Cirrhosis in Children :

Report of a Single Center from Southern Iran

Sayed Mohsen Dehghani, Mohammad Hadi Imanieh, Mahmood haghihat,
Abdorrasoul Malekpour, Zeinab Falizkar
Middle East Journal of Digestive Disease.2013;5:41-6
Dipresentasikan oleh :
Roro Rukmi Windi Perdani

Pembimbing :
Dr. I. Hartantyo, SpAK
Dr. Ninung Rose DK, M.Si.Med., SpAK

Introduction
Cirrhosis in children

is a diffuse process characterized by progressive

hepatic fibrosis, distortion of the hepatic architecture
and formation of regenerative nodules
uncommon in the pediatric age group
Chronic cholestasis, inborn errors of metabolism and
chronic hepatitis are the main causes
83 children:
biliary atresia
(27.7%), cryptogenic
cirrhosis (24.1%)

cryptogenic cirrhosis
and autoimmune
hepatitis

Introduction ...(2)
Complication of
cirrhosis hepatis

asci
tes

jaund
ice

GI
varic
eal
bleed
ing
spontan
eous
bacterial
peritonit
is

hepatic
encephalo
pathy

ede
m

ed
em

Hepatopulmo
nary and
hepatorenal
syndrome

Material and Method

All cirrhotic
children aged less
than 18 years who
referred to an
outpatient
pediatric
gastroenterology
clinic affiliated
with Shiraz
University of
Medical Sciences
between March
2009 and
September 2010

Clinical
examination
Data form
contain :
demographic,
clinical and
paraclinical data

Laboratory test :
serum
ceruloplasmin,
24-hour urine
for copper,
anti-nuclear,
anti-smooth
muscle,
anti-liver kidney
microsomal type
1 antibodies,
HBs antigen,
ANTI-HBC
antibody,
ANTI-HCV
antibody,
sweat chloride
test,
alfa-1
antitrypsin
genotyping,
serum
succinylacetone

Radiographic :
ultrasonography
or computed
tomography scan;
hepatobiliary
scintigraphy;
Histopathologic :
liver biopsy

Material and Method...(2)

Cirrhosis with unknown etiology :

cryptogenic
Cirrhosis diagnosed by USG findings :
heterogeneous liver with coarse
echo with or without nodule
formation and irregular borders

acute hepatitis and cirrhotic livers

were not definitively established
were excluded from the study

106 children with documented liver

cirrhosis for etiologies and
complications of cirrhosis

106

94

12

liver biopsyproven
cirrhosis

liver biopsy-not
done due to
coagulopathy

Material and Method...(3)

Severity of liver disease
Child-Pugh classification, Pediatric End-stage Liver
Disease (PELD) score : < 12 years
Model for End-stage Liver Disease (MELD) : > 12
years

Material and Method...(4)

Complications of cirrhosis
Jaundice was diagnosed clinically as yellowish discoloration of sclera and skin
Ascites was diagnosed according to physical findings such as abdominal flank bulge with
fluid, fluid wave, shifting dullness, a ballotable liver and spleen, umbilical and inguinal
hernia and ultrasonographic evidence of ascites
Hepatic encephalopathy was diagnosed clinically as irritability, lethargy, acute change in
mental status, neurodevelopmental delay, school problems, sleep reversal, ataxia, and
tremors
Esophageal varices were diagnosed endoscopically
Abdominal paracentesis with polymorphonuclear cells more than 250/mm3 was considered to
be diagnostic of spontaneous bacterial peritonitis
Hepatopulmonary syndrome was diagnosed as arterial oxygen pressure of <70 mmHg in
air with alveolar/arterial gradient of >20 mmHg

Analisis
ANOVA , students t-test
SPSS

room

Result
106 subjects
a mean age of 8.24 6.12
years (range: 5 months to 18
years)
60 cases were boys (56.6%)
and 46 were girls (43.4%)
mean PELD/MELD scores were
14.2 11.9 (range: 6-48)
mean Child-Pugh score was
8.1 2.2 (range: 5-13)
27% : grade A
44% : grade B
29% : grade C

Most common causes cof irrhosis hepatis

Wilson disease (n=22; 20.7%)
biliary atresia (n=19; 17.9%)
cryptogenic cirrhosis (n=14; 13.2%)
Other causes were autoimmune hepatitis (n=12;
11.3%)
idiopathic neonatal hepatitis (n=10; 9.4%)
Hepatorenal tyrosinemia (n=9; 8.5%)
glycogen storage disease (n=6; 5.7%)
progressive familial intrahepatic cholestasis (n=4;
3.8%)
paucity of bile ducts (n=3; 2.8%)
cardiac cirrhosis, choledocal cyst and primary
sclerosing cholangitis (2 cases for each one; 1.9%)
Carolis disease in one child (0.9%)
infection (n=0; 0%)

Most common complication of cirrhosis hepatis

jaundice (n=72; 67.9%)
ascites (n=47 ; 44.3%)
Non-bleeding esophageal varices (n=
32 children; 30.2%)
gastrointestinal variceal bleeding (n=
17 ; 16.1%)
hepatic encephalopathy (n=13; 12.7%)
edema (n=8; 7.5%)
spontaneous bacterial peritonitis (n=5;
4.7%)
hepatopulmonary syndrome (n=5;
4.7%)
Hepatorenal syndrome was not present
in any children with liver cirrhosis
no complication (n=19 ;17.9%)

Result...(2)

Result...(3)

Discussion...(3)

The most common causes of liver cirrhosis in this study were

Wilson disease (20.7%), biliary atresia (17.9%), cryptogenic cirrhosis
(13.2%), and autoimmune hepatitis (11.3%)
might be because it has become an active pediatric liver transplant
center in the Middle East region with more than 70 pediatric liver
transplants her parts of the country
In a recent study from Iran the most common hepatic diseases among
inpatients were hepatitis B virus (HBV) and cryptogenic or
nonalcoholic fatty liver disease induced cirrhosis
In another study from Southern Iran HBV infection was the major
cause for cirrhosis and ascites was the most common complication in
adult patients

 Other study :Tunisian study (36 girls and 35 boys): most

frequent clinical signs : jaundice and hepatomegaly
Most etiology : biliary causes (biliary atresia, choledocal
cysts, progressive familial intrahepatic cholestasis) (40%)
Other etiology : hepatorenal tyrosinemia, Wilson disease
(17%) and post-hepatitis cirrhosis (17%)
No definite etiology : 27% of cases
because of the lack of availability of some specific tests

In Iran : main indications for liver

transplantation in children :
Wilson disease (20.3%),
cryptogenic cirrhosis (16.7%),
autoimmune cirrhosis
(14.5%)
agreed with the results of this
study.

Bernard: chronic cholestasis starting in early infancy,

chronic hepatitis, and metabolic disorders : main causes of
cirrhosis in children
recommend :
precise identification of the cause for effective therapy
close follow-up is necessary for prolonging life and to
prevent
diagnose and manage complication on time if liver
transplantation is not effective

Discussion ...
Northern India

Brazil

235 children with hepatobiliary disorders:

acute hepatitis (28%), chronic liver
disease (36%), neonatal cholestasis
syndrome (26%),

Most common causes of

cirrhosis hepatis :

Chronic liver diseases : post-hepatitic

cirrhosis (13%), Wilson disease (21%),
autoimmune (4%), and non-Wilsonian
metabolic diseases (16%)

biliary atresia (50%),

autoimmune disorders (20.5%)
and cryptogenic (17.6%)

Other study

Most common cause of

chirrhosis hepatis
metabolic disorders,
most common causes of
cholestatic
syndrom,
liver cirrhosis :
most common indications for liver
autoimmune hepatitis

transplantation : biliary atresia

(30%), fulminant hepatic failure
( 27%) and autoimmune cirrhosis
(16%)

Argentina

progressive familial intrahepatic

cholestasis (30), fibrocystic
diseases of the liver and kidneys
(21%)

Oman

Japan : (33379 patients with liver cirrhosis at 58 hospitals) :

most common causes : hepatitis B virus (13.9%), hepatitis C virus (60.9%),
alcohol (13.6%), primary biliary cirrhosis (2.4%) and autoimmune hepatitis
(1.9%)
In this center : (Saberifiroozi et al.): 480 adult patients (mean age: 39 13years;
68.1% men) on the liver transplantation, most common causes : cryptogenic
(143; 29.9%) and hepatitis B virus (127; 26.5%)
These studies : different causes of liver cirrhosis in children and adults
as the most common cause of liver cirrhosis in adults : viral hepatitis.
in the current study : no cases of viral hepatitis

Complication

Conclusion
This study concluded that metabolic disorders (Wilson disease, hepatorenal
tyrosinemia), cholestatic syndromes (biliary atresia, idiopathic neonatal
hepatitis, progressive familial intrahepatic cholestasis), and autoimmune
hepatitis : most common causes of cirrhosis in children
Early diagnosis and determining the common causes of cirrhosis
effective treatment and decreasing the rate of complications and mortality

EVIDENCE BASED MEDICINE

RESEARCH QUESTION
to report the causes of liver cirrhosis and evaluate its
complications in children

P
I
C
O

Seberapa jauh penelitian yang sudah dilakukan?

Sudah ada penelitian tentang diagnosis sirosis hepatis
Penelitian di beberapa negara menunjukkan :
Penyebab utama sirosis hepatis :
Argentina : biliary atresia (30%), fulminant hepatic failure (
27%) and autoimmune cirrhosis (16%)
Brazil : biliary atresia (50%), autoimmune disorders
(20.5%) and cryptogenic (17.6%)
Oman : progressive familial intrahepatic cholestasis (30),
fibrocystic diseases of the liver and kidneys (21%)

Penelitian ini : penyebab utama sirosis hepatis :

Wilson disease (20.7%), biliary atresia (17.9%),
cryptogenic cirrhosis (13.2%), and autoimmune
hepatitis (11.3%)

Apa hasil penelitian?

Simpulan

Penyebab utama sirosis hepatis : kelainan metabolik (Wilson disease,

hepatorenal tyrosinemia), cholestatic syndromes (biliary atresia, idiopathic
neonatal epatitis, progressive familial intrahepatic cholestasis), dan
autoimmune hepatitis
Deteksi dini dan penentuan penyebab utama sirosis : untuk tatalaksana
efektif dan menurunkan komplikasi dan kematian

VALIDITY, IMPORTANCE, APPLICABILITY

VALIDITY
Siapakah sampelnya dan bagaimana metode samplingnya?

Pasien rawat jalan berusia kurang dari 18 tahun di klinik raw

at jalan gastroenterologi yang berafiliasi dengan Fakultas Ke
dokteran Universitas Shiraz Maret 2009-September 2010
Metode sampling : consecutive sampling
Apakah pasien bisa dideteksi dan dimulai pengamatan pada saat
yang sama/seragam dalam perjalanan penyakitnya?
tidak

VALIDITY(2)
3.

Apakah kriteria diagnosis, derajat penyakit, morbiditas, keadaan

demografi yang digunakan untuk inklusi dijabarkan dengan j
elas?
Tidak dijabarkan dengan jelas

4. Apakah kriteria keluaran telah ditetapkan dan digunakan denga

n baik? ya
5. Apakah kriteria dapat digunakan/diterapkan pada pelayanan kes
ehatan kita dengan akurat?
Tidak, karena alat laboratorium di RS ini belum lengkap

IMPORTANCE
Seberapa besar efek dan kepentingan klinis dar
i
penelitian ini ?
Penelitian ini memberi referensi tentang pen
yebab utama, gejala klinis, dan komplikasi si
rosis hepatis
pada anak
Apakah hasil penelitian ini dapat menjawab
permasalahan di lingkungan saya?
ya

APPLICABILITY
Apakah keadaan pasien saya sangat berbeda dengan
penelitian tersebut ?
Untuk usia dapat diterapkan pada pasien di RSDK
Hasil penelitian belum dapat diterapkan karena keterbatasan
pemeriksaan laboratorium

Apakah ada halangan dalam penerapan hasil

penelitian tersebut?
iya ada halangan, di RSDK belum ada alat laboratorium

Apakah hasil penelitian dapat diterapkan dengan

mudah di lingkungan saya?
tidak

TERIMA KASIH

MOHON MASUKAN