Dipresentasikan oleh :Roro Rukmi Windi Perdani

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

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 cir-rhosis (24.1%)

cryptogenic cirrhosis and

autoimmune hepatitis

Introduction ...(2)

jaundice

ascites

GI variceal bleedin

g

hepatic encephalopat

hy

edemspontaneo

us bacterial

peritonitis

edem

Hepatopulmonary and

hepatorenal syndrome

Complication of cirrhosis

hepatis

Material and Method

All cirrhotic children aged less than 18

years who re-ferred to an outpatient

pediatric gas-troenterology clinic affiliated

with Shiraz University of Medical Sci-ences be-

tween March 2009 and Sep-tember 2010

● Clinical examination● Data form contain : de-mographic, 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 : ▪ultrasonogra-phy or com-

puted tomogra-phy scan; ▪ hep-

atobiliary scintigraphy;

Histopathologic : ▪ liver biopsy

• Cirrhosis with unknown etiology : cryptogenic

• Cirrhosis diagnosed by USG find-ings : heterogeneous liver with coarse echo with or without nodule formation and ir-regular borders

• acute hepatitis and cirrhotic livers were not definitively es-tablished were excluded from the study

• 106 children with documented liver cirrhosis for etiologies and complications of cirrhosis

Material and Method...(2)

106

94 12

liver biopsy-not done due to coagulopathy

liver biopsy-proven cirrhosis

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

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 room air with alveolar/arterial gradient of >20 mmHg

Complications of cirrhosis

Material and Method...(4)

Analisis

ANOVA , student’s t-test SPSS

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 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%)

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%)▪ Caroli’s disease in one child (0.9%)▪ infection (n=0; 0%)

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%), cryp-togenic 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 non-alcoholic fatty liver disease induced cirrho-sisIn another study from Southern Iran HBV infection was the ma-jor 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 hep-atomegaly

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 spe-cific tests

In Iran : main indications for liver transplantation in chil-dren : 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

235 children with hepatobiliary disor-ders:

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

Chronic liver diseases : post-hep-atitic cirrhosis (13%), Wilson dis-ease (21%), autoimmune (4%), and non-Wilsonian metabolic dis-eases (16%)

Northern India

Argentina

Brazil

Oman

Other studyMost common cause of chirrhosis hepatis metabolic disorders,

cholestatic syndrom, autoim-

mune hepatitis

most common indications for liver transplantation : biliary atresia (30%), fulminant he-patic failure ( 27%) and au-toimmune cirrhosis (16%)

Most common causes of cirrhosis hepatis :

biliary atresia (50%), autoimmune disorders (20.5%) and cryptogenic (17.6%)

most common causes of liver cirrhosis :

progressive familial intrahep-atic cholestasis (30), fibrocys-tic diseases of the liver and kidneys (21%)

Discussion ...

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

Cirrhosis hepatis

GI bleeding

Jaundice

Hepatic encephalopathy

Ascites

Bacterial infections

Complication

Conclusion

This study concluded that metabolic disorders (Wilson disease, hepa-torenal tyrosinemia), cholestatic syndromes (biliary atresia, idio-pathic 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

POPULATION : seluruh penderita sirosis hepatiis pada anak berusia kurang dari 18 tahun yang dirujuk ke klinik rawat jalan gastroenterologi yang berafiliasi dengan Fakultas Kedokteran Universitas Shiraz pada Maret 2009 hingga September 2010

INTERVENTION : tidak dilakukan

COMPARISON : tidak ada

OUTCOME : karakteristik pasiien sirosis hepatis, penyebab utama, gejala klinis dan komplikasi sirosis hepatis

P

I

C

O

Apakah desain penelitian sudah menjawab pertanyaan penelitian

• Sudah

Ke mana penelitian ditujukan?

• Penderita anak dengan sirosis hepatis

Apakah PICO sudah cukup?

• Sudah

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?

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 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%)

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%)▪ Caroli’s disease in one child (0.9%)▪ infection (n=0; 0%)

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, APPLICABIL-ITY

VALIDITY

• Siapakah sampelnya dan bagaimana metode samplingnya?

Pasien rawat jalan berusia kurang dari 18 tahun di klinik rawat

jalan gastroenterologi yang berafiliasi dengan Fakultas

Kedokteran 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, morbidi-

tas, keadaan demografi yang digunakan untuk

inklusi dijabarkan dengan jelas?

Tidak dijabarkan dengan jelas

4. Apakah kriteria keluaran telah ditetapkan dan

digunakan dengan baik? ya

5. Apakah kriteria dapat digunakan/diterapkan pada

pelayanan kesehatan kita dengan akurat?

Tidak, karena alat laboratorium di RS ini belum lengkap

IMPORTANCE

Seberapa besar efek dan kepentingan klinis dari penelitian ini ?

• Penelitian ini memberi referensi tentang penyebab utama, gejala klinis, dan komplikasi sirosis hepatis pada anak

Apakah hasil penelitian ini dapat men-jawab 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

MOHON MASUKANTERIMA KASIH