HEPATITIS

Diagnosis & pengobatan

Dr.WAN NEDRA Sp.A
Child Health Dept.
School of Medicine
University of YARSI

 organ paling
besar
Fungsi utama:
1. Regulasi
Metabolite
dalam dara
2.Detoxikasi

Spleen

Unconj
bilirubin

Old
Erythrocytes
Small amount
entero-hepatic
circulation

Conj.
bilirubin
Urobilinogen

Regenerate jk
terjadi kerusakan
HEPATITIS
Inflammasi &
necrosis
Infeksi & non Inf

Stercobiline

MASALAH:
Medico-psycho-sosio-economics
Morbidity - mortality
Epidemiology endemic area
carrier rate - transmission rate
Therapeutics ?
Quality of life?
Prevention - !!!

OBJECTIVES:
PRINCIPLES - MANAGEMENT
Epidemiology, virology, patophysiology:
Diagnosis DINI
Supportive & monitoring
Detection dini:
fulminant, chronicity
Prevention of spreading
Pengobatan Antivirus

HEPATITIS A - G
HAV

HBV

HCV

Virus

Picorna

Hepadna Flavi

Inkubasi

15-40 hr 50-160hr 1-5 bln

Onset

Akut

HGV
Flavi
? 2 mg

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

CTL

Hepatocyte

Receptor

Excretion in stool

HAV Pathogenesis

Excretion in
bile

HAV infection
Asymptomatic

Non icteric

Complication -

Relapsing

Icteric
Cholestatic

Resolved
Transplantation
Death

OUTCOME
HAV infection

Liver failure

SEROLOGIC DIAGNOSIS

Symptoms

Anti HAV total

ALT

HVA
stool

IgM-Anti HVA

Months of exposure

EPIDEMIOLOGI HEPATITIS A
Heat stable virus
Endemic - reservoir
Fecal-oral, kontak erat
High risk: children, CLD cases, etc
Susceptible: High sosio-economic
population

PENCEGAHAN HEPATITIS A
Hygiene - sanitation
Proper cooking, hand washing, septic
tank,diapers, etc
Isolate index case
Immunization
Pre-post exposure
(activepassive)

IgM anti HAV (+)

PT/INR
INR < 2
Repeat LFTs 57 d

INR > 2
Not improved
(clinic-laboratory)

Improved

Repeat LFT 6wk

Normal
No follow up

Abnormal

Refer

PENCEGAHAN
VAKSIN HVA
Inactivated, safe

Long immunity
Simultaneous other vaccine
Interchangeable
Serologic test:
pre- likely exposed
post- vaccination: (-)

Individual risk: Children,

CLD cases, IVDU,
homosexuals
multitransfused,
household contact,
traveler - low endemic
Professional risk: food
sector, health, sewage,
waste water, in contact
with children, labmilitary staff

Routine vs Post-exposure
PROPHYLAXIS
Age
ys
<2

Routine immunization

Individual Community
protection
Vaccine (-)

2 18 Havrix 720 EU, Avaxim 160

AU/ml, 2x (0, 6 12)
> 18

Havrix 1440 EU, Avaxim

160 AU/ml, 2x (0, 6 12)

Post-exposure
immunization
NHIG household
contact
Vaccine or
Vaccine & NHIG#
None or Vaccine or
Vaccine & NHIG#

Protective anti HAV 20 mIU/ml

PRE-EXPOSURE PROPHYLAXIS
(Travelers to endemic area)

AGE
(ys)
<2

DURATION
protection

RECOMMENDATION

< 3 months

NHIG 0.02 ml/kg, 1x

3-5 months

NHIG 0.02 ml/kg, 1x

Long term
< 3 months

NHIG 0.06 ml/kg, repeat 5/12

Vaccine or NHIG (0.02 ml/kg)

3-5 months

Vaccine or NHIG (0.06 ml/kg)

Long term

Vaccine

Initial consultation:
consultation
- LFTs
- Anti HAV-IgM
- HBsAg

Bilirubin
> 6 mg/dl

Bilirubin
> 6 mg/dl

GGT cholestatic or
obstruction

Alanine transaminase
IgM HAV
(+)

Treat as
HAV

Refer

IgM HAV
()

Refer

Refer

HEPATITIS B VIRUS
Diagnosis & Pengobatan

PENDAHULUAN
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
chronic - 95%
HCC children

HBsAg prevalence
> 8% - High
2-7%: Moderate
< 2% - Low

UI: HBV-HCC
8/16 (3 ys old)

Transfusion
Transplantation

Vertikal,
ibubayi
Intravenous
drug users

Medics/
paramedics
Multiple
sexual
partners

PARENTERALLY
TRANSMITTED

Prisoners,
institutional

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
1st Trimester
3rd Trimester

ACUTE HVB CHRONIC HVB

10%
10%
60-70%

At birth
1st five years
Risiko:
HBeAg (-) 22 76% :
DNA fulminan ?!
HBsAg (+) cord, siblings

31 90%
80-85%
50%

TRANSMISSION HORIZONTAL vs
CAIRAN TUBUH

Faeces

HBV

HBsAg

Infectivity

(-)

Bile,
pancreas

(-),

Saliva

(+)

(+)

replicate (+)
Percutan

Semen-

(+)

(+)

IV

Low

Low

No

vaginal fluid

Collustrum

SERODIAGNOSIS VHB
Acute HBV infection with recovery
Serologic course

Acute

symptoms

HBsAg

Progression to Chronic HBV infection

Serologic course
(6 months)

Total anti HBc

IgM anti
HBc

Anti
HBs

Weeks after exposure

Chronic
(years)

HBsAg

IgM anti
HBc

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

Initial

HBs HBe IgM IgG Anti Anti DNA

Ag Ag
HBc HBc HBs HBe
+
+
+
+

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
HVA, HVC,
lain2

Drugs, toxin
(acetaminophen
etc)

HBsAg (+)

Acute hepatitis

Acute HBV
HBsAg, IgM
antiHBc

Reactivation

chronic
HBV

Exacerbation
chronic
HBV,
ch

eAg conversion

Differential diagnosis HBV

VAKSINASI VHB
Cutting chain of transmission
Bayi, Remaja

Pd daerah endemic -
infeksi maternal
Infeksi dini chronic
reservoir
HCC pd semua umur
Provide protection
adolescent - risk

Dewasa High risk

Dialysis, transfused
IVDU, homosex, active
heterosexuals
Household contacts of
HBV carriers
Health care worker

Eliminasi VHB, menurunkan HCC

The only vaccine against CANCER

HBV particle
S
domain

Anti HBs
neutralizing
antibody
(HBIG)
PASSIVE

HBV virion

Quick-short immunity
Segera, IM, safe
Acute exposure:
Newborn HBV mother
Occupational
Sexual contact
Household contact

HBsAg
immuno
genic
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

PEMERIKSAAN SEROLOGIC

Not recommended for infants - children

PREVACCINATION
Kemungkinan :
Populasi High risk
Remaja
Daerah endemic
Anggota keluarga
HBV carriers
Health care staff

POSTVACCINATION
Infants - HBsAg (+)
mothers
High risk newborns
Immunodeficient
Dialysis patients
Health care workers

Dosis yg di-Rekomendasikan

Booster not recommended for any group

GROUP
(yrs)

VACCINE
HBvax-II Engerix-B Uniject
5 g/

10 g/

HepavacGene
10 g/ 0.5 ml

Adults > 20 ys

0.5 ml
10 g/

0.5 ml
20 g/

Dialysis

1 ml
40 g/

1 ml
40 g

Infant, children,
adolescents

2 ml

IMMUNISASI VHB
PD BAYI
HBsAg
Mother

Immunization
Active

(+)
(-)

Passive
Active

Active*

Dose

Schedule

Engerix-B,Uniject 10 g

12 hours,

HBVax-II 5 g

month 1,6

HBIg 100 U -0.5 ml

Engerix-B,Uniject 10 g

SEGERA

HBVax-II 2.5 g

BW 2kg

Engerix-B,Uniject 10 g

Age 2 mo
12 hours,

HBVax-II 5 g

month 1,6

POST-EXPOSURE
Sexual contact acute or HBV carrier
EXPOSED
SOURCE:
CONTACT
ACUTE HBV
Unvaccinated/ HBIG 0.06 ml/kg or
Anti HBs (-)

HBIG & vaccine or

Vaccinated

test if high risk

None

Unknown
anti HBs test

Anti HBs (-):

HBIG & vaccine

SOURCE:
CARRIER
HBIG &
vaccine
Or test
None
Similar
application

POST-EXPOSURE to BLOOD
HBsAg-HBeAg (+)
clinical hepatitis 22 31%
sero-evidence HBV 37 61%

Exposed

Treatment if

Vaccine, AB

HBsAg +

HBsAg ??

Unvaccinated/
AB response ?

HBIG-vaccine or
test if high risk

Vaccine or
Test if high risk

None

None

Responder

source is

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
Th/

N
IFN ()

other antivirus ?!

IFN

N
IFN

Observed

INFEKSI KRONIK VHB

(HBsAg positive > 6 months)

HBeAg

DNA +

+ -

LFT N

Th/ IFN ()

IFN

other antivirus

IFN Observ?! 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

(acute phase)
Resolved

HIV and
alcohol

Chronic
Stable

Slowly
progressive

Cirrhosis

HCC
Transplant
Death

SEROLOGI
HVC AKUT - RESOLVED
Anti
VHC

symptom

SEROLOGI
HVC KRONIK
symptom
VHC RNA

VHC RNA

SGPT

SGPT
Normal

Months

Anti
HVC

Normal

Years

Months

Years

PENCEGAHAN
High rate of mutation vaccine (-)

Umum VHB
Screening:
Donor, ANAK
IBU CARRIER,
IVDU, close contact,
sexual behavior,
multi-transfused,
medical staff ,
LTx recipient

SPESIFIK
Identifikasi kasus baru:
ibu hamil, ibu yg VHC +,
hepatitis kronik, HCC,
cirrhosis, ALT ?
SC ?!
Immunisasi (-) ?

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
Offer th/

Moderate-severe
Th/ 3/12

Mild
Observed
Repeat biopsy

Refused

Follow-up

Prefer Th/ Repeat PCR

(+)
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