Penyakit Hati pada Anak

Wan Nedra
Child Health Dept.School of
Medicine
University of YARSI
 Objective:

• Hepatitis Virus: A, B, C
• Kolestasis
• Latihan Penyelesaian Kasus
 Hepar
• Organ paling besar
Fungsi utama:
1. Regulasi Metabolite dalam
darah
2.Detoxikasi
Regenerate jk terjadi kerusakan
HEPATITIS:
Inflammasi & necrosis
 Infeksi & non Inf
MASALAH: Medico-psycho-sosio-economics
 HEPATITIS A - G

HAV HBV HCV HGV

Virus Picorna Hepadna Flavi Flavi

Inkubasi 15-40 hr 50-160hr 1-5 bln ? 2 mg

Onset Akut Subklinik Subklinik Akut/sub

Oral-fekal (++) (-) (-) (-)
Parenteral Jarang (++) (++) (++)
Kronisitas (-) (+) (+) (+)
HEPATITIS A (HAV)
Heat stable virus
 HEPATITIS A (HAV)
Prolong, relapsing, liver failure (0.1%)

Complication in chronic liver disease – 8x

Self
limiting
disease

Single
exposure

Long life
immunity Endemic - young children – reservoir
 Morbidity – mortality at older age
 Excretion in
bile

HAV Pathogenesis
 HAV infection

Asymptomatic Non icteric Icteric

Complication - Relapsing Cholestatic Liver failure

Resolved

Transplantation

Death

OUTCOME
HAV infection
SEROLOGIC DIAGNOSIS

Symptoms
Anti HAV total
ALT

HVA
stool IgM-Anti HVA

Months of exposure
 PENCEGAHAN HEPATITIS A

 Hygiene - sanitation
• Proper cooking, hand washing, septic
tank,diapers, etc
• Isolate index case
• Immunization:
Pre-post exposure (active–passive)
IgM anti HAV (+)

PT/INR

INR < 2 INR > 2 Refer

Repeat LFTs 5–7 d Not improved

(clinic-laboratory)

Improved

Repeat LFT 6wk Abnormal

Normal –
No follow up
 PENCEGAHAN
VAKSIN HVA
• Individual risk: Children,
CLD cases, IVDU,
Inactivated, safe homosexuals
multitransfused,
household contact,
• Long immunity traveler - low endemic
• Simultaneous - • Professional risk: food
other vaccine sector, health, sewage,
• Interchangeable waste water, in contact
with children, lab-
• Serologic test: military staff
pre- likely exposed
post- vaccination: (-)
 Routine vs Post-exposure
PROPHYLAXIS

Age Routine immunization Post-exposure

ys Individual  Community immunization
protection
<2 Vaccine (-) NHIG – household
contact
2 – 18 Havrix 720 EU, Avaxim 160 Vaccine or
AU/ml, 2x (0, 6 – 12) Vaccine & NHIG#
> 18 Havrix 1440 EU, Avaxim None or Vaccine or
160 AU/ml, 2x (0, 6 – 12) Vaccine & NHIG#

Protective – anti HAV  20 mIU/ml

 PRE-EXPOSURE PROPHYLAXIS
(Travelers to endemic area)

AGE DURATION RECOMMENDATION

(ys) protection
<2 < 3 months NHIG 0.02 ml/kg, 1x
3-5 months NHIG 0.02 ml/kg, 1x
Long term NHIG 0.06 ml/kg, repeat 5/12
2 < 3 months Vaccine or NHIG (0.02 ml/kg)
3-5 months Vaccine or NHIG (0.06 ml/kg)
Long term Vaccine
Initial consultation:
consultation Bilirubin Refer
- LFTs > 6 mg/dl
- Anti HAV-IgM
- HBsAg

Bilirubin  GGT – cholestatic or

> 6 mg/dl
obstruction

 Alanine transaminase
Refer

IgM HAV IgM HAV

(+) (–)

Treat as Refer
HAV
 HEPATITIS B & C VIRUS
Diagnosis & Pengobatan
• Virus Hepatitis B (VHB) telah meng infeksi 350 Juta
orang di dunia
• HBV salah satu penyebab utama hepatitis kronis &
karsinoma hepatoseluler (KHS), menyebabkan 1 juta
kematian / th
• Risiko kronis jauh lebih besar bila infeksi terjadi pd awal
kehidupan dibanding dg dewasa, pd bayi risiko kronisitas
90%, 25-30 % akan sirosis hep atau ca.hepatoseluler.
Pd keadaan ini tanpa gejala (asimtomatis)
• Cara yg paling efektif mengontrol VHB:Imunisasi
• Diperlukan pemahaman strategi pemakaian vaksin yg
efektif
 Karrier HBV di Asia > 350.000  78%
Indonesia: Moderate – high endemic
! Prevention: Kontrol Infeksi, immunisasi &
skreening ibu hamil

Transmisi 
Early Infection
HBsAg prevalence
chronic - 95% > 8% - High
UI: HBV-HCC
2-7%: Moderate
HCC – children < 2% - Low 8/16 (3 ys old)
 Transfusion Vertikal,
Transplantation ibubayi
Intravenous
drug users
Medics/
paramedics

Multiple Prisoners,
sexual institutional
partners PARENTERALLY
TRANSMITTED
 KEMUNGKINAN CARA
PENULARAN YG LAIN: kelompok

• Anggota keluarga – Carrier HBV

• Homosexuals, prostitutes – customers
• Prone to injury e.g. Personel ABRI
• Pengobatan – accupunctur, dialysis
• Tattoo, tindik
 Transmisi MATERNAL
Major route – pd daerah endemic

TIMING ACUTE HVB CHRONIC HVB

1st Trimester 10% 10%
3rd Trimester 60-70% 31 – 90%
At birth 80-85%
1st five years 50%
Risiko: HBeAg (-) 22 – 76% :
DNA  – fulminan ?!
HBsAg (+) cord, siblings
 TRANSMISSION HORIZONTAL vs
CAIRAN TUBUH

HBV HBsAg Infectivity

Faeces (-) Bile, (-),
pancreas replicate (+)
Saliva (+) (+) Percutan

Semen- (+) (+) IV

vaginal fluid
Collustrum Low Low No
 SERODIAGNOSIS VHB
Acute HBV infection with recovery Progression to Chronic HBV infection
Serologic course Serologic course
Acute Chronic
symptoms (6 months) (years)

HBsAg
HBsAg Total anti HBc

IgM anti Anti

HBc HBs
IgM anti
HBc

Weeks after exposure Weeks after exposure

HBsAg TES YG PLG SERING UNTUK DETEKSI INF
VHB AKUT/PEJAMU KRONIS. BILA ANTIGENMIA LBH
DARI 6 BLN PASN DIKATAKAN PENGIDAP KRONIS
 DIAGNOSIS
AKUT VHB

HBs HBe IgM IgG Anti Anti DNA

Ag Ag HBc HBc HBs HBe
Initial + + + - +

Window - + +/-

Resolved - + + + -
 DIAGNOSIS
KRONIK VHB

HBs HBe IgM IgG Anti Anti DNA

Ag Ag HBc HBc HBs HBe
Replicate + + + - +

Non Repl + + + -

Flare up + +/- + + - +

PreCore + - + - + +
mutant
 Superinfection Drugs, toxin
HVA, HVC, (acetaminophen
lain2 etc)

HBsAg (+)
Acute hepatitis

Acute HBV Reactivation Exacerbation

HBsAg, IgM chronic chronic
ch HBV,
antiHBc HBV eAg conversion

Differential diagnosis HBV

 VAKSINASI VHB
Cutting chain of transmission

Bayi, Remaja Dewasa High risk

• Pd daerah endemic -  • Dialysis, transfused
infeksi maternal • IVDU, homosex, active
• Infeksi dini  chronic – heterosexuals
reservoir • Household contacts of
• HCC pd semua umur HBV carriers
• Provide protection – • Health care worker
adolescent - risk

 Eliminasi VHB, menurunkan HCC

 The only vaccine against CANCER
Anti HBs – HBsAg
HBV particle
neutralizing immuno
S
antibody domain genic
(HBIG)

HBV virion

PASSIVE
• Quick-short immunity
• Segera, IM, safe
• Acute exposure:
Newborn HBV mother
Occupational
Sexual contact
Household contact
ACTIVE
• Long term immunity
• Deep IM (deltoid,
thigh); safe
• Seroconvert 95%
• Protects (10 mIU/ml)
min 12 ys – booster (-)
• Lapsed: proceed
• Can be – other vaccine
 IMMUNISASI VHB PD BAYI

HBsAg Immuni- Dose Schedule

Mother zation
Active Engerix-B,Uniject 10 g 12 hours,
(+) HBVax-II 5 g month 1,6
Passive HBIg 100 U -0.5 ml
(-) Active Engerix-B,Uniject 10 g SEGERA
HBVax-II 2.5 g BW  2kg
Age  2 mo
? Active* Engerix-B,Uniject 10 g 12 hours,
HBVax-II 5 g month 1,6
 POST-EXPOSURE
Sexual contact – acute or HBV carrier

EXPOSED SOURCE: SOURCE:

CONTACT ACUTE HBV CARRIER
Unvaccinated/ HBIG 0.06 ml/kg or HBIG &
Anti HBs (-) HBIG & vaccine or vaccine
test if high risk Or test
Vaccinated None None
Unknown – Anti HBs (-): Similar
anti HBs test HBIG & vaccine application
 POST-EXPOSURE to BLOOD
HBsAg-HBeAg (+)
 clinical hepatitis 22 – 31%
sero-evidence HBV 37 – 61%

Exposed Treatment if source is

Vaccine, AB HBsAg + HBsAg ??
Unvaccinated/ HBIG-vaccine or Vaccine or
AB response ? test if high risk Test if high risk
Responder None None
Non HBIG x2 or High risk source:
responder HBIG-vaccine As in HBsAg (+)
 VACCINE NONRESPONDERS
< 5% vaccinees – persistent non-responders

• Complete the 2nd series of 3 doses

• Usual schedule
• Retest 1 – 2 months after completion
• CEK STATUS HBsAg & HBeAg
• If exposed, treat as nonresponder with
postexposure prophylaxis
 DECISION MAKING

HBeAg + -

DNA + + -

LFT N   N

Th/ IFN (–) IFN IFN Observ-

other antivirus ?! ed
 INFEKSI KRONIK VHB
(HBsAg positive > 6 months)

HBeAg + -

DNA + + -

LFT N   N

Th/ IFN (–) IFN IFN Observ-

other antivirus ?! ed
 INTERFERON – LAMIVUDINE
Anti replication, immune modulator,
anti proliferation

  DNA (-), HBsAg (-)

Normalization ALT - histology
Infection – symptoms – progressivity -
HCC 
 Risk transmission , survival 
• Indication:
ALT > 1.5x N, hep injury, HBsAg- DNA (+)
• Predictors: low DNA, non cirrhotic, short
duration, non vertical trans., female
 HEPATITIS Virus C
Diagnosis & pengobatan
VIRUS HEPATITIS C (VHC)
The silent killer
• Intrafamilial 4.3%; sexual 5%
• Transmisi VERTIKAL 6% (2-11%)
FAKTOR RISIKO: TITER RNA IBU,
FAKTOR obstetric: RNA  (13 vs 6%),
viremia +/- (8 vs 3%), Pervaginam/SC (6
vs 0%)
• BAYI - ANTI VHC – SETELAH LAHIR 
7/12
 VHC PASCA TRANFUSI
All donors
HBsAg
Screening
donor
HIV - risk
Anti HIV
SGPT/Anti HBc

Anti VHC

Years
PATHOPHYSIOLOGY
• Liver injury :
cytopathic
respon IMUN
• Chronicity 85% - Th2 > Th1
• Slow onset – cirrhosis decade 3 – 4
• HCC – menyebabkan cirrhosis
 Exposure HIV and
(acute phase) alcohol

Resolved Chronic

Stable Cirrhosis

Slowly HCC
progressive Transplant
Death
 SEROLOGI SEROLOGI
HVC AKUT - RESOLVED HVC KRONIK
Anti Anti
symptom VHC symptom HVC

VHC RNA VHC RNA

SGPT SGPT

Normal Normal

Months Years Months Years

 PENCEGAHAN
High rate of mutation – vaccine (-)
Umum  VHB • SPESIFIK
Screening: • Identifikasi kasus baru:
Donor, ANAK ibu hamil, ibu yg VHC +,
IBU CARRIER, hepatitis kronik, HCC,
IVDU, close contact, cirrhosis, ALT – ?
sexual behavior, • SC ?!
multi-transfused, • Immunisasi (-) ?
medical staff ,
LTx recipient
 VAKSIN VHC
MASIH BELUM DITEMUKAN

Kegagalan penemuan vaksin

• Which is the neutralizing antibody
• E2, CAP, NS3 peptide?
• E2 – highly mutational
Tidak dapat meng-identifikasi antigen peptide
– yg mem-produksi respon imun yg adekuat

!!
Prevention
 VHC – RNA
biopsi Hati

Cirrhosis Moderate-severe Mild

Offer th/ Th/ 3/12 Observed

Repeat biopsy
Refused Prefer Th/ Repeat PCR

Follow-up (+) (-)

Stop Th/ Th/ 1 yr
 ANTIVIRUS
INTERFERON - RIBAVIRINE
• Mekanisme - Indikasi  VHB
• Response: Poor  25% -  mutation
• Predictor:
hepatitis (ALT ) > asymptomatic
durasi pendek > durasi panjang -
akut?!
viremia rendah, HIV (-), Fe hati 
FINAL MESSAGE

• Get yourself vaccinated

• Get your family vaccinated
• Get your patients vaccinated
• Get your community vaccinated
• Spread the knowledge
Let’s work – hand in hand
to overcome the problem

TERIMA KASIH-SELAMAT BELAJAR