Hepatitis Virus

Stefanus Gunawan

Bagian Ilmu Kesehatan Anak

Fakultas Kedokteran Universitas Sam Ratulangi
Rumah Sakit Umum Prof.Dr. RD Kandou
Manado
 Hepatitis Virus - Sejarah

“ Infeksius” A Transmisi
E
Enterik

Hepatitis NANB
Virus

Transmisi
“ Serum” B D C Parenteral

F, G, TTV
? lain2
 Hepatitis
proses radang/inflamasi hati
• Berbagai penyebab:
– Obat-obatan
– Toksin
– Alkohol
– Infeksi virus (A, B, C, D, E, dll)
– Infeksi lain2 (parasit, bakteri)
– Faktor fisik
Virus Hepatitis A
 Virus Hepatitis A

• Picornavirus (RNA)  Heparnavirus

• Hospes alami: hanya Manusia
• Stabil pada pH rendah
• Inaktivasi oleh suhu tinggi,formalin,
klorin
 Epidemiologi Hepatitis A
• Reservoir Manusia. Endemik

• Transmisi Fekal-oral

• Pola musiman Tidak ada

• Masa tular 2 minggu sebelum s/d

1 minggu pasca awitan
 Transmisi Virus Hepatitis A
• Kontak personal erat
(e.g., kontak serumah, kontak sex, tempat
penitipan anak)
• Kontamisasi makanan & minuman
(e.g., pesaji sakit, kerang2an tak masak)
• Blood exposure (rare)
(e.g., injecting drug use, transfusion)
 Global Patterns of
Hepatitis A Virus Transmission

Disease Peak Age

Endemicity Rate of Infection Transmission Patterns

High Low to Early Person to person;

High childhood outbreaks uncommon
Moderate High Late Person to person;
childhood/ food and waterborne
young adults outbreaks
Low Low Young adults Person to person;
food and waterborne
outbreaks
Very low Very low Adults Travelers; outbreaks
uncommon
 Patogenesis Hepatitis A
• Masuk melalui mulut
• Replikasi virus di hati
• Virus pada darah & feses 10-12 hari
pasca infeksi
• Ekskresi Virus sampai > 3 minggu setelah
awitan gejala
 Gambaran Klinis Hepatitis A
• Masa inkubasi 28 hari (rentang 15-50 hari)
• Gejala tidak khas/spesifik hepatitis A
• Gejala klinis berhubungan dengan usia
• Anak umumnya asimtomatis, dewasa
simtomatis
 Gambaran Klinis Hepatitis A

 Ikterus menurut usia <6 th: <10%

6-14 th: 40%-50%
>14 th: 70%-80%

 Komplikasi: Hepatitis Fulminan

Hepatitis Kolestatik
Relapsing hepatitis
 Sekuele kronis: Tidak ada
 Hepatitis A Infection
Typical Serological Course

Symptom Total anti-

s HAV

Titre ALT

Fecal
HAV
IgM anti-HAV

0 1 2 3 4 5 6 1 2
2 4
Months after exposure
 Diagnosis Laboratorik

• Diagnosis Infeksi Akut : deteksi HAV-IgM

dalam serum secara EIA.
• Infeksi lama / imunitas: deteksi HAV-IgG
secara EIA.
 Strategi Vaksinasi Hepatitis A
Pertimbangan Epidemiologis

• Banyak kasus outbreak di masyarakat

– Sebagian besar kasus tidak diketahui faktor

risiko
– Tersering pada usia 5-14 tahun

– Anak-2 : reservoir infeksi

• Orang berisiko tinggi infeksi

– Travelers
– Lelaki homosexual
– Pesalah guna obat/injeksi
 Vaksin Hepatitis A

• Inactivated whole virus

• HAVRIX (GlaxoSmithKline)
• AVAXIM (AventisPasteur)
• Formula Pediatrik & Dewasa
• Dianjurkan untuk usia >2 tahun
 Vaksin Hepatitis A

Anak & Remaja

– 1 dosis
– Booster 6-12 bulan setelah dosis
pertama
– Imunogenitas
• >97% seropositif setelah dosis I
• 100% seropositif setelah dosis 2
 Vaksin Hepatitis A
Efek Simpang

• Nyeri pada lokasi injeksi

• Reaksi sistemik jarang
• Tidak ada laporan efek simpang berat
 Vaksin Hepatitis A
Kontraindikasi & Peringatan

• Reaksi alergi berat terhadap komponen

vaksin atau setelah dosis pertama
• Sakit akut sedang atau berat
Hepatitis B Virus
 Virus Hepatitis B
• Famili Hepadnaviridae (DNA)
• Terdiri banyak komponen antigenik
• Manusia  satu-2nya hospes
• Infeksius selama + 1 bulan pada suhu
kamar
 Virus Hepatitis B
HBsAg

HBcAg

HBeAg
 Infeksi Virus Hepatitis B

• >200 juta karier di dunia

• Penyebab hepatitis kronis & sirosis
• Human carcinogen— penyebab
80% karsinoma hepatoselular
 Epidemiologi Hepatitis B

• Reservoir Manusia, Endemik

• Transmisi Bloodborne
Subclinical cases transmit

• Communicability 1-2 bulan sebelum

& setelah awitan gejala
Karier kronik
 Global Patterns of Chronic
HBV Infection
• High (>8%): 45% of global population
– lifetime risk of infection >60%
– early childhood infections common
• Intermediate (2%-7%): 43% of global population
– lifetime risk of infection 20%-60%
– infections occur in all age groups
• Low (<2%): 12% of global population
– lifetime risk of infection <20%
– most infections occur in adult risk groups
 Kadar Virus Hepatitis B dalam
berbagai cairan tubuh

Rendah/
Tinggi Moderat Tak terdeteksi
darah semen urin
serum cairan vagina feses
eksudat luka saliva keringat
air mata
ASI
Transmisi Hepatitis B Perinatal*

• Jika ibu positif HBsAg & HBeAg

– 70%-90% bayi terinfeksi
– 90% dari bayi terinfeksi menjadi karier kronik
• Jika ibu hanya positif HBsAg
– 20% bayi terinfeksi
– 90% dari bayi terinfeksi menjadi karier kronik

*pada kasus tanpa profilaksis pasca pajanan

 Cara Penularan Virus Hepatitis
B

 Seksual – pekerja seksual & homoseksual paling

berisiko.
 Parenteral - IVDA, Petugas Kesehatan berisiko
tinggi.
 Perinatal – Ibu dengan HBeAg positif lebih
berisiko menularkan penyakit ke anaknya
dibanding yang HBe negatif. Transmisi perinatal
berperan penting pada populasi dengan
prevalensi tinggi.
 Gambaran Klinis Hepatitis B
• Masa inkubasi: 6 minggu - 6 bulan (rerata
120 hari)
• Prodromal nonspesifik: demam, malaise,
sakit kepala, mialgia
• Gejala sakit tidak spesifik untuk hepatitis
B
• + 50% infeksi asimtomatik
 Gambaran Klinis
Hepatitis B
 Clinical illness (ikterus): <5 yrs: <10%
5 yrs: 30%-50%
 Acute case-fatality rate: 0.5%-1%
 Infeksi kronis: <5 yrs: 30%-90%
5 yrs: 2%-10%
 Mortalitas dini karena
penyakit hati kronis: 15%-25%
 Spektrum Hepatitis B Kronik

1. Hepatitis Kronik Persisten -

asimtomatik
2. Hepatitis Kronik Aktif – simtomatik,
eksaserbasi hepatitis
3. Sirosis Hepatis
4. Karsinoma Hepatoselular
Komplikasi Hepatitis B

• Hepatitis Fulminan
• Sirosis Hepatis
• Karsinoma Hepatoselular
• Kematian
 Acute Hepatitis B Virus Infection with
Typical Recovery
Serologic Course
Symptoms
HBeAg anti-HBe

Total anti-HBc
Titre

HBsAg IgM anti-HBc anti-HBs

0 4 8 12 16 20 24 28 32 36 52 100

Weeks after
 Progression to Chronic Hepatitis B Virus
Infection Course
Typical Serologic
Acute Chronic
(6 months) (Years)
HBeAg anti-HBe
HBsAg
Total anti-HBc
Titr
e

IgM anti-HBc

0 4 8 12 16 20 24 28 32 36 52 Years
Weeks after Exposure
 Outcome of Hepatitis B Virus
100 Infection 100
by Age at Infection
80
Chronic Infection (%)

80

Symptomatic Infection (%)

60 60
Chronic Infection

40 Chronic Infection (%) 40

20 20

Symptomatic Infection
0 0
Birth 1-6 months 7-12 months 1-4 years Older Children
and Adults
Age at Infection
 Diagnosis

• HBsAg – petanda umum infeksi.

• HBsAb – petanda kesembuhan dan/atau imunitas terhadap
infeksi HBV.
• anti-HBc IgM – petanda infeksi akut.
• anti-HBcIgG – infeksi lampau atau kronis.
• HBeAg – petanda replikasi aktif virus & daya infeksi.
• Anti-Hbe - virus tidak lagi bereplikasi. Tetapi pasien dapat
tetap positif HBsAg (yang diproduksi oleh HBV utuh).
• HBV-DNA – petanda replikasi aktif virus, lebih akurat
daripada HBeAg terutama pada kasus escape mutants.
Digunakan untuk monitor respon terhadap terapi.
 Pengobatan (kronis)

• Interferon - pada karier HBeAg +ve hepatitis

kronik aktif. Response rate: 30 to 40%.
• Lamivudine - nucleoside analogue reverse
transcriptase inhibitor. Toleransi & respons cukup
baik. Cenderung relaps saat henti obat. Resistensi
obat cepat timbul.
• Keberhasilan pengobatan: hilangnya HBsAg,
HBV-DNA, dan serokonversi ke HBeAg.
 Pencegahan

• Vaksinasi - vaksin rekombinan

• Hepatitis B Immunoglobulin - proteksi
orang yang terpajan hepatitis B. Efektif
diberi dalam 48 jam. Diberikan ke
neonatus dengan ibu HBsAg dan/atau
HBeAg positif.
• Lain-2 – skrining donor darah, hati-2
pemakaian darah & cairan tubuh.
 Vaksin Hepatitis B

• Komposisi Recombinant HBsAg

• Efektivitas 95% (Rentang 80%-100%)

• Durasi imunitas >15 tahun

• Jadwal 3 Dosis

• Booster doses not routinely recommended

 Proteksi* menurut umur & dosis

Dosis Bayi** Remaja & Dewasa***

1 16%-40% 20%-30%
2 80%-95% 75%-80%
3 98%-100% 90%-95%

* Titer antibodi Anti-HBs > 10 mIU/mL

** Bayi Prematur <2 kg berspon kurang terhadap vaksinasi
*** Faktor-2 yang menurunkan respon vaksin : usia >40
tahun, lelaki, merokok, obesitas, dan defisiensi immun
 Recomendasi Dosis
Vaksin Hepatitis B

Dosis (mcg)
Bayi & 0.5 mL (10)
anak <11 tahun

Remaja 11-19 tahun 0.5 mL (10)

Dewasa >20 tahun 1.0 mL (20)

Efektivitas Jangka Panjang
Vaksin Hepatitis B

• Memori Imunologis terbentuk setelah

vaksinasi
• Paparan terhadap VHB membangkitkan
reaksi anamnestik anti-HBs
• Infeksi kronis jarang dijumpai pada
responder pasca-vaksinasi
 Hepatitis B Vaccine

Routine booster doses

are NOT routinely
recommended for any
group
 Vaksinasi Hepatitis B
Jadwal Rutin pada Bayi

Dosis Interval
Usia lazim
Minimum
Primer 1
Primer 2 0-2 bulan --
Primer 3 1- 4 bulan 4 minggu
6-18 bulan 8 minggu*

*dan minimal 16 minggu setelah dosis pertama

 Bayi Berat Lahir Sangat Rendah
• Bayi <2000 gram berespon buruk
terhadap vaksin
• Tunda dosis pertama sampai usia
kronologis 1 bulan jika ibu HBsAg negatif
• Dosis pertama segera setelah lahir +
HBIG jika ibu HBsAg positif
 Prevensi Infeksi
Virus Hepatitis B Perinatal
• Mulai pengobatan dalam 12 jam pasca
lahir
• Vaksin Hepatitis B (dosis pertama) dan
HBIG pada lokasi yang berlainan
• Lengkapi jadwal vaksinasi pada usia 6
bulan
• Tes respon pada usia 9-15 bulan
 Vaksin Hepatitis B
Reaksi Simpang
Bayi &
Dewasa Anak
Nyeri pada lokasi suntikan 13%-29% 3%-9%
Keluhan sistemik ringan 11%-17% 0%-20%
(fatigue, nyeri kepala)

Temperatur >99.9°F (37.7°C) 1% 0.4%-6%

Reaksi sistemik berat jarang jarang

 Vaksin Hepatitis B
Kontraindikasi & Peringatan

• Reaksi alergi berat terhadap

komponen vaksin atau setelah dosis
sebelumnya
• Sakit akut moderat atau berat
 Hepatitis C Virus

capsid envelop protease/helica RNA- RNA

e se dependent polymerase
protein
c2 33c c-
2 100
5’ 3’

cor E1 E2 NS NS NS NS
e 2 3 4 5

hypervariable
region
 Hepatitis C - Clinical
Features
Incubation period: Average 6-7 wks
Range 2-26 wks
Clinical illness (jaundice): 30-40% (20-30%)
Chronic hepatitis: 70%
Persistent infection: 85-100%
Immunity: No protective
antibody
response identified
 Chronic Hepatitis C Infection

• The spectrum of chronic hepatitis C infection is

essentially the same as chronic hepatitis B
infection.
• All the manifestations of chronic hepatitis B
infection may be seen, albeit with a lower
frequency i.e. chronic persistent hepatitis, chronic
active hepatitis, cirrhosis, and hepatocellular
carcinoma.
 Hepatitis C Virus Infection
Typical Serologic Course
anti-
HCV
Symptom
s

Titr
e

ALT

Norma
l
0 1 2 3 4 5 6 1 2 3 4
Mont Years
hsTime
after
Exposure
 Risk Factors Associated
with Transmission of
HCV
 Transfusion or transplant from infected donor
 Injecting drug use
 Hemodialysis (yrs on treatment)
 Accidental injuries with needles/sharps
 Sexual/household exposure to anti-HCV-positive
contact
 Multiple sex partners
 Birth to HCV-infected mother
 Laboratory Diagnosis

• HCV antibody - generally used to diagnose hepatitis C

infection. Not useful in the acute phase as it takes at least 4
weeks after infection before antibody appears.
• HCV-RNA - various techniques are available e.g. PCR and
branched DNA. May be used to diagnose HCV infection in
the acute phase. However, its main use is in monitoring the
response to antiviral therapy.
• HCV-antigen - an EIA for HCV antigen is available. It is
used in the same capacity as HCV-RNA tests but is much
easier to carry out.
 Prevention of
Hepatitis C
 Screening of blood, organ, tissue donors

 High-risk behavior modification

 Blood and body fluid precautions

 Treatment

• Interferon - may be considered for patients with

chronic active hepatitis. The response rate is
around 50% but 50% of responders will relapse
upon withdrawal of treatment.
• Ribavirin - there is less experience with ribavirin
than interferon. However, recent studies suggest
that a combination of interferon and ribavirin is
more effective than interferon alone.
 Hepatitis D (Delta)
 antigenVirus HBsAg

RNA
 Hepatitis D - Clinical
Features
 Coinfection
– severe acute disease.
– low risk of chronic infection.
 Superinfection
– usually develop chronic HDV infection.
– high risk of severe chronic liver disease.
– may present as an acute hepatitis.
 Hepatitis D Virus
Modes of
Transmission
 Percutanous exposures
 injecting drug use
 Permucosal exposures
 sex contact
 HBV - HDV Coinfection
Typical Serologic Course
Symptoms

ALT
Elevated

Titre
anti-HBs
IgM anti-
HDV

HDV RNA

HBsAg
Total anti-HDV

Time after
 HBV - HDV Coinfection
Typical Serologic Course
Symptoms

ALT
Elevated
Titre
anti-
IgM anti- HBs
HDV

HDV RNA

HBsAg
Total anti-
HDV

Time after
 HBV - HDV
Superinfection
Typical Serologic
Course
Jaundice

Symptoms

Total anti-HDV
ALT
Titre

HDV RNA
HBsAg

IgM anti-HDV

Time after Exposure

 Hepatitis D -
Prevention
 HBV-HDV Coinfection
Pre or postexposure prophylaxis to prevent
HBV infection.
 HBV-HDV Superinfection
Education to reduce risk behaviors among
persons with chronic HBV infection.
Hepatitis E Virus
 Hepatitis E - Clinical Features

 Incubation period: Average 40 days

Range 15-60 days
 Case-fatality rate: Overall, 1%-3%
Pregnant women,
15%-25%
 Illness severity: Increased with age
 Chronic sequelae: None identified
 Hepatitis E Virus
Infection
Typical Serologic Course
Symptom
s

ALT IgG anti-HEV

Titer IgM anti-HEV

Virus in stool

0 1 2 3 4 5 6 7 8 9 1 1 1 1
0 1 2 3
Weeks after
 Hepatitis E Virus
Infection
Typical Serologic Course
Symptom
s

ALT IgG anti-HEV

Titer IgM anti-HEV

Virus in stool

0 1 2 3 4 5 6 7 8 9 1 1 1 1
0 1 2 3
Weeks after
 Hepatitis E -
Epidemiologic
Features
 Most outbreaks associated with faecally contaminated drinking
water.
 Several other large epidemics have occurred since in the Indian
subcontinent and the USSR, China, Africa and Mexico.
 In the United States and other nonendemic areas, where
outbreaks of hepatitis E have not been documented to occur, a
low prevalence of anti-HEV (<2%) has been found in healthy
populations. The source of infection for these persons is
unknown.
 Minimal person-to-person transmission.
 Prevention and Control Measures
for Travelers to HEV-Endemic
Regions
 Avoid drinking water (and beverages with ice) of
unknown purity, uncooked shellfish, and uncooked
fruit/vegetables not peeled or prepared by traveler.
 IG prepared from donors in Western countries
does not prevent infection.
 Unknown efficacy of IG prepared from donors in
endemic areas.
 Vaccine?
 Type of Viral Hepatitis
A B C D E

Source of feces blood/ blood/ blood/ feces

virus blood-derived blood-derived blood-derived
body fluids body fluids body fluids

Route of fecal-oral percutaneous percutaneous percutaneous fecal-oral

transmission permucosal permucosal permucosal

Chronic no yes yes yes no

infection

Prevention pre/post- pre/post- blood donor pre/post- ensure safe

exposure exposure screening; exposure drinking
immunization immunization risk behavior immunization; water
modification risk behavior
modification
Thank You