KULIAH HEPAOTOLOGI ANAK Debora S. Liana, dr., Sp.

SEMESTER V FK UNDANA 17-12-2015

1
PEMBAHASAN KULIAH HEPATOLOGI ANAK
1. Neonatal cholestasis

2. Neonatal hyperbilirubinemia

3. Hepatitis virus

2
 NEONATAL CHOLESTASIS
DEFINITION:
as conjugated hyperbilirubinemia developing
within the first 90 days of extrauterine life.
Conjugated bilirubin exceeds 1.5 to 2.0
mg/dl, OR
Conjugated bilirubin generally exceeds 20%
of the total bilirubin.

3
METABOLISME BILIRUBIN

( T. Lissauer& A. Fanaroff, Neonatology at a glance. Ed. 1, 2006)

4
NEONATAL CHOLESTASIS
Intra-hepatic Ekstra-hepatic

Hepatocyte Bile duct

Bile duct injury or obstruction

Metabolic Viral Idiopatic

neonatal
hepatitis - Extrahepatic billiary atresia
- Choledocal cyst

Intra hepatic bile duct hypoplasia or paucity

5
A. Extrahepatic bile duct
 Biliary atresia
 Choledochal cyst dan chioledohocele
 Biliary hipoplasia
 Choledocholithiasis
 Bile duct perforation
 Neonatal sclerosing cholangitis
B. Intrahepatic bile duct
 Syndromic paucity
 Nonsyndromic paucity
• Hypothyroidism
• Bile duct dysgenesis
 Congenital hepatic fibrosis
• Ductal plate malformation
• Polycystic kidney disease
• Caroli’s disease
• Hepatic cyst
 Cystic fibrosis
 Langerhans’ cell histiocytiosis
 Hyper-IgM syndrome
C. Hepatocytes
 Sepsis-associated cholestasis
 Neonatal hepatitis
Viral inf : Hepatitis B, CMV, Herpes viruses, Adenovirus, Enterovirus
 Syphilis
 Toxoplasmosis
 Progressive familial intrahepatic cholestasis syndromes
 Bile acid synthetic defects
 Urea cycle defects
 Fatty acid oxidation disorders
 Mithocondrial enzymopathies
 Peroxisomal disorders(zellweger syndrome)
 Carbohydrate disorders
• Galactosemia
• Hereditary fructose intolerance
• Glycogen storage disease
 Lipid storage disorders
• Niemann-Pick cell disease
• Gaucher’s disease
• Wolman’s disease
 1-Antitrypsin deficiency
 Neonatal hemochromatosis
 Total parenteral nutrition-associated cholestasis
6
 Kolestasis Neonatal

Anamnesis : BBLR, riwayat penyakit keluarga, tinja kuning

Klinis : tampak sakit

YA TIDAK
Kolestasis intrahepatik Kolestasis ekstrahepatik

Pemeriksaan penyaring: USG

• TORCH
Nondiagnostik Diagnostik
• Infeksi bakteri
• Metabolik
Skintigrafi Pembedahan
Ekskresi (+) (Tumor, kista, striktur)
Diagnostik
TIDAK YA
Neonatal hepatitis
Biopsi hati Reevaluasi penyebab
(Proliferasi duktuli) Kolestasis intrahepatik

Kolangiografi operatif

Operasi Kasai
7
 COMMON ETIOLOGIES CLINICAL PRESENTATION
 Premature infants  Jaundice
 Sepsis/Acidosis
 Scleral icterus
 TPN-associated
 Drug-induced  Hepatomegaly

 Idiopathic neonatal hepatitis  Acholic stools

 Extrahepatic biliary atresia  Dark urine

 Alpha-1-antitrypsin deficiency  Other signs and symptoms

depend on specific disease
 Intrahepatic cholestasis syndromes process

8
TREATMENT
1. Medical management 2. Surgical management
1. Nutritional support 1. Kasai procedure for biliary atresia

2. Treatment of pruritus 2. Limited bile duct resection and re-

3. Choleretics and bile acid-binders anastomosis

4. Management of portal 3. Choledochal cyst excision

hypertension and its consequences 4. Cholecystectomy

5. Liver transplantation

9
TREATMENT Management of portal hypertension and
its consequences
Nutritional support 1. Variceal bleeding
 Supplemental calcium and phosphate when bone  Fluid rescuscitation
disease is present
 Blood products
 Prophylaxis for zinc deficiency
 Sclerotherapy
 Low-copper diet as poorly excreted
 Balloon tamponade
 Sodium restriction when ascites present
 Portovenous shunting
 Propanolol
Treatment of pruritus 2. Ascites
 Bile acid-binders: cholestyramine, cholestipol  Sodium restriction
 Ursodeoxycholic acid  Diuretics: spironolactone, furosemide
 Phenobarbital as a choleretic  Albumin
 Naloxone  Paracentesis
 Rifampin 3. Thrombocytopoenia
 managed with platelet infusions when
clinically indicated

10
EXTRAHEPATIC BILIARY ATRESIA
 Generally acholic stools with onset at about 2 weeks-old
 Average birth weight
 Hepatomegaly with firm to hard consistency
 Female predominance
 No well-documented familial cases
 Normal uptake on radionucleotide scan with absent excretion
 Biopsy shows bile duct proliferation, bile plugs, portal or perilobular fibrosis and
edema, and intact lobular structure

11
KASAI PROCEDURE
1. Performed for biliary atresia that is not surgically correctable with excision
of a distal atretic segment.
2. Roux-en-Y portoenterostomy
3. Bile flow re-established in 80-90% if performed prior to 8 weeks-old.
4. Bile flow re-established in less than 20% if performed after 12 weeks-old
5. Success of the operation is dependent on the presence and size of ductal
remnants, the extent of the intrahepatic disease, and the experience of the
surgeon.
6. Complications are ascending cholangitis and reobstruction as well as failure
to re-establish bile flow.

12
LIVER TRANSPLANTATION
1. Survival rates approach 80% at 1 year and 70% at 5 years.

2. Biliary atresia is the most common indication for transplant and may be the
initial treatment when detected late or may be used as a salvage
procedure for a failed Kasai.

3. Used early in cases of tyrosinemia.

13
NEOATAL HYPERBILIRUBINEMIA
14
 Ikterus : akumulasi bilirubin  kulit & atau sklera kuning
 Dewasa : serum bilirubin > 2 mg/dl (> 17 mol/L)
 Neonatus : serum bilirubin > 5 mg/dl (> 86 mol/L)
 Ikterus Patologis :
 Timbul dalam 24 jam I
 Bilirubin ↑ > 5 mg/dL dalam 24 jam
 ’Cut off levels’
 > 15 mg/dL pada bayi cukup bulan
 > 7 mg/dL pada bayi kurang bulan
 Ikterus menetap
 > 8 hari pada bayi cukup bulan
 > 14 hari pada bayi kurang bulan

15
Normogram Bhutani untuk Hiperbilirubinemia

(Roberton, Manual of neonatal intensive care, 4th, 2002)

16
 Bilirubin  ensefalopati bilirubin
1. Derajat 1 : letargis, hipotonia, mengisap lemah
2. Derajat 2 : febris, hipertonia, opistotonus
3. Derajat 3 : gejala/tanda derajat 2 makin 
 Gejala sisa :
1. gangguan pendengaran sensorineural
2. palsi serebral koreoathetoid
3. ’gaze abnormalities’

17
KADAR BILIRUBIN DARAH
’ Unconjugated’ ’ Conjugated ’
Bilirubin Indirek Direk

Larut dalam air (-) (+)

Larut dalam lemak (+) (-)
Bersenyawa dengan (+) (-)
albumin
Bilirubin bebas Toksik di otak Tidak

18
COMMON CAUSES

( T. Lissauer& A. Fanaroff, Neonatology at a glance. Ed. 1, 2006)

19
 Tanya dan Lihat Tanda / Gejala Klasifikasi

Mulai kapan ikterus? Ikterus segera setelah lahir

Ikterus pada hari pertama
Ikterus pada usia ≥ 14 hari
IKTERUS PATOLOGIS
Daerah mana yang Ikterus lutut/siku/lebih
ikterus?
Bayi kurang bulan
Bayi kurang bulan?
Tinja pucat
Warna tinja?
Ikterus usia 3-13 hari IKTERUS FISIOLOGIS

Tanda patologis (-)

(Buku Bagan MTBM, Depkes RI, 2001) 20
 DIAGNOSIS TATALAKSANA
Anamnesis Terapi sinar
Pemeriksaan Fisik  Status hidrasi dan pemberian minum
Laboratorium
 Monitoring kadar bilirubin
• bilirubin total, direk, indirek
 Transfusi Tukar
• golongan darah dan rhesus ibu dan bayi
• darah lengkap dan hapusan darah  Obat-obatan

• hitung retikulosit • Phenobarbital

• tes Coombs direk • Intra venous immunoglobulin
• skrining G6PD • Mettaloporphyrins
• kadar albumin • Cholestyramin
21
MANAGEMENT OF HYPERBILIRUBINEMIA
Terapi sinar Transfusi Tukar

Bayi sehat Faktor Risiko* Bayi sehat Faktor Risiko*

Usia mg/dL  mol/L mg/dL mol/L mg/dL  mol/L mg/dL mol/L

Hari 1 Setiap ikterus yang terlihat 15 260 13 220
Hari 2 15 260 13 220 25 425 15 260
Hari 3 18 310 16 270 30 510 20 340
Hari 4 20 340 17 290 30 510 20 340
dst
* American Academy of Pediatrics, Subcommittee on hyperbilirubinemia, Management of hyperbil in NB, 2004)

22
 TERAPI SINAR
 Penghentian terapi sinar :
 Bayi cukup bulan bilirubin ≤ 12 mg/dL (205 mol/dL)
 Bayi kurang bulan bilirubin ≤ 10 mg/dL (171 mol/dL)
 Bila timbul efek samping
• Efek samping terapi sinar :
 Enteritis
 Hipertermia
 Dehidrasi
 Kelainan kulit
 Gangguan minum
 Bronze baby syndrome
 Kerusakan retina

23
 TRANFUSI TUKAR
Berat Bayi (gram) Tidak Komplikasi Rasio Bili/Alb Ada Komplikasi Rasio Bili/Alb
(mg/dL) (mg/dL)
< 1250 13 5.2 10 4

1250 – 1499 15 6 13 5.2

1500 – 1999 17 6.8 15 6

2000 – 2499 18 7.2 17 6.8

≥ 2500 20 8 18 7.2

* American Academy of Pediatrics, Subcommittee on hyperbilirubinemia, Management of hyperbil in NB, 2004)

24
HEPATITIS VIRUS
25
HEPATITIS
• Bacteria, Virus, Parasite
• Chemical agents: drugs, poison
INFLAMATION
• Auto-immune NECROSIS
• Systemic proses: ischemic, SIRS
• etc

26
VARIATION OF STAGING
 Lack of resolution of symptoms (WL,
fatigue, anorexia, hepatomegaly)
 Failure of Bilirubin , LFT, Glucose to
normal (Within 6-12m)
 Persistence HBs Ag beyond 6 mo or
HBe Ag beyond 3 mo
CHRONIC  Presence of bridging or multilobular
FULMINANT necrosis

ANICTERIC

ASIMPTOMATIK
27
CLINICAL LABORATORY
Very mild, asymptomatic
 Serum bilirubin: 5-20 mg/dl
Anicteric:
 Direct bil  indirect bil
 GIT symptoms
 Influenza like symptoms
 AST/SGOT, ALT/SGPT increase 5-10X

 Usually remains undiagnosed  Alk. phosphatase : mild elevation (3x)

Icteric  PT is usually normal: in severe hepatitis,
 Prodromal period PT is prolonged
 Jaundice 1-4 weeks  Hypoglycemia
 Recovery

28
HEPATITIS A (HAV)
 Age: 5-15 years
 Communicability: 2 weeks before illness until 1 week after appearance of jaundice
 Prognosis: excellent “no chronicity”
 Viral Transmission:
• Close personal contact (e.g., household contact, sex contact, child day care
centers)
• Contaminated food, water (e.g., infected food handlers, raw shellfish)
• Blood exposure (rare) (e.g., injecting drug use, transfusion)
 Diagnosis:
 HAV Ab IgM persists for 2-6 months
 IgG Ab means immunity
29
  Incubation period: Average 30 days
Range 15-50 days
 Jaundice by age group:
• <6 yrs  <10%
• 6-14 yrs  40%-50%
• >14 yrs  70%-80%
 Complications:
 Fulminant hepatitis
 Cholestatic hepatitis
 Relapsing hepatitis
 Chronic sequelae:None

Group Age No Doses Dose Months

HEPATITIS A VACCINE
2-18y 2 im 0.5ml 0,6-12
Children & adolescent

Adults
>18y 2 im 1 ml 0,6-12

30
HEPATITIS B VIRUS
Incubation period: Average 60-90 days (45-180 days)
MODE OF TRANSMISSION
 Sexual - sex workers and homosexuals
 Parenteral - IVDA, Health Workers
 Perinatal - Mothers who are HBeAg positive >> transmit to their offspring 
Perinatal transmission is the main means of transmission in high prevalence populations
Clinical illness (jaundice):
 <5 yrs  <10%
 5 yrs  30%-50%

Acute case-fatality rate: 0.5%-1%

Chronic infection:
 <5 yrs  30%-90%
 5 yrs  2%-10%
31
 Hepatocellular Carcinoma

Cirrhosis of Liver

Chronic Active Hepatitis - symptomatic

exacerbations of hepatitis

Chronic Persistent Hepatitis -

asymptomatic

From Murray et. al., Medical Microbiology 5th edition, 2005, Chapter 62, published by Mosby Philadelphia

32
DIAGNOSIS MARKER HBV
HBsAg - general marker of infection
HBsAb - document recovery and/or
immunity
Anti-HBc IgM - acute infection
Anti-HBcIgG - past or chronic infection
HBeAg - replication of virus and
therefore infectiveness
Anti-Hbe - no longer replicating
HBV-DNA - active replication, accurate
than HBeAg monitoring response to
therapy

33
 Mother-to-child transmission by HBeAg status
in HBsAg-positive Mother

Number of % of
Number
Status tested positive positive
tested
babies babies

HBsAg-positive mothers 120 25 21

HBeAg-positive mothers (100%) 15 94
HBeAg-negative 16 (13%) 10 10
mothers 104 (87%)

http://www.cdc.gov/ncidod/diseases/hepatitis
 Hepatitis B Vaccination Schedule

Infant whose mother is Infant whose mother is not Older child,

infected with Hepatitis B infected with Hepatitis B adolescent or
virus virus adult

within 12 hours Birth-2 months

First dose any time
of birth of age

1-2 months 1-4 months of age (at least 1-2 months

Second dose
of age 1 month after first dose) after first dose

6 months 6-13 months 4-6 months

Third dose
of age of age after first dose

http://www.cdc.gov/ncidod/diseases/hepatitis
HEPATITIS B IMMUNOPROPHYILAXIS TO PREVENT PERINATAL TRANSMISSION

 Infant born to mother known to be HBsAg positive , OR

Infant born to mother not screened for HBsAg
Vaccine dose Age of infant
First Birth (within 12 hours)
HBIG If mother is found to be HBsAgpositive, administer dose to
Infant as soon as possible, not later than 1 week
after birth
Second 1-2 months
Third 6 months

36
ACUTE ABDOMEN
37
ACUTE ABDOMEN
Life-Threatening Causes:
Trauma
Appendicitis
Intussusception
Marotation with midgut volvulus
Ectopic pregnancy
Uncommon life-threatening causes:
Incacerted inguinal hernia
Adhesions with intestinal obstruction
Necrotizing enterocolitis
Peptic ulcer disease
Common Causes
Gastrointestinal infection
Constipation
Colic
Foreign body ingestion
Rupture ovarian cyst
Other infections ( UTI, Streptococcal pharyngitis,
pneumonia, viral illnesses, PID, mesenteric
lymphadenitis)

38
 • The cause of visceral pain :
tension in the muscle fibers
(stretching of the wall, spasm
of the muscle or stretching of
Viceral pain the capsule of the organ).
(Splanchnic pain)
• Pain associated with
obstruction is severe and
cramping, intermittent (colic).
• Ischemia of visceral muscle :
pain because the gut loses
Parietal pain motility and becomes
(Somatic pain )
Referred pain ) distended.
• Visceral pain of ischemic
origin is caused most often by
strangulation of the bowel in
hernia or volvulus.
39
PATTERNS OF PAIN IN ACUTE ABDOMINAL CONDITIONS

40
CLINICAL EVALUATION
History
Age
Trauma ?
Symptoms (vomiting / greenish,
fecal, diarrhea, fever )
Flatus
Psychology ?

41
DANGER SIGNS
Abdominal distension. Arthritis, perirectal disease
Persistent vomiting – greenish-fecal. Failure to thrive
Gastrointestinal bleeding Disuria – hematuria
Hepatomegali, splenomegali Respiratory problem
Trauma history
Abdominal pain, cause?
FUO

PKB IKA X , Bali 2010 42

TERIMAKASIH
43