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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 E
Transmisi
Enterik

Hepatitis Virus NANB

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
Symptoms Total anti-
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 Recovery
Typical 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 Exposure


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

IgM anti-HBc

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

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 >99.9F (37.7C) 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 envelope protease/helicase RNA- RNA polymerase


protein dependent

c22 33c c-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
Symptoms

Titre

ALT

Normal
0 1 2 3 4 5 6 1 2 3 4
Month Years
s Time 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) Virus
antigen 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 Exposure


HBV - HDV Coinfection
Typical Serologic Course
Symptoms

ALT Elevated

Titre
anti-HBs
IgM anti-HDV

HDV RNA

HBsAg
Total anti-HDV

Time after Exposure


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
Symptoms

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 Exposure
Hepatitis E Virus Infection
Typical Serologic Course
Symptoms

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 Exposure
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