VIRAL HEPATITIS

Nining Sri Wuryaningsih

Bagian Patologi Klinik FK UNS

 Largest Organ
Main functions:
1. Metabolite
regulation
in blood
2. Detoxication

Spleen

Unconj
bilirubin

Old
Erythrocytes
Small amount
entero-hepatic
circulation

Conj.
bilirubin
Urobilinogen

Regenerate if
damaged
HEPATITIS
Inflammation &
necrosis
Infection & non

Stercobiline

PROBLEMS
Medico-psycho-sosio-economics

Morbidity - mortality
Epidemiology endemic area
carrier rate - transmission rate
Therapeutics ?
Quality of life?
Prevention - !!!

OBJECTIVES:
PRINCIPLES - MANAGEMENT
Epidemiology, virology, patophysiology:

Early Diagnosis

Supportive & monitoring

Early detection:

fulminant, chronicity

Prevention of spreading

Antivirus treatment

HEPATITIS A - G
HAV

HBV

HCV

HGV

Virus

Picorna

Hepadna

Flavi

Flavi

Incubation

15-40
days

50-160

1-5
months

? 2 weeks

Onset

Acute

days
Subclinic Subclinic Acute/sub

Oral-fecal

(++)

(-)

(-)

(-)

Parenteral

Rare

(++)

(++)

(++)

Chronicity

(-)

(+)

(+)

(+)

HBV Carriers > 350 juta 78% in Asia

Indonesia: Moderate high endemic (3-20%)
! Prevention: Infection control & immunization ASAP
Maternal screening

Amirudin et al, 1991 Ujung Pandang: 7,1%

Sulaiman et al 1995: prevalence 8,8%
Van Hattum et al, 2003, Riau: 1,9%

Transmission
Early Infection
chronic - 95%

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

Newborn of
HBV mothers --

Transfusion
Transplantation,dial
lysis,accupuncture

(2,1-6,7%)

Intravenous
Drug users,
Tattoo,ear
piercing

Medics/
paramedics
Family members
HBV carriers

Multiple
sexual
partners/h
omosexual
s

PARENTERALLY
TRANSMITTED

Prone to
injury:army;Pris
oners,
institutional,

MATERNAL TRANSMISSION
Major route - in endemic area
TIMING
1st Trimester
3rd Trimester
At birth

ACUTE HVB CHRONIC HVB

10%
10%
60-70%

31 90%
80-85%

1st five years

50%
Risk: HBeAg (-) 22 76%: Anti HBe (+)
fulminant !!!

HORIZONTAL TRANSMISSION vs
BODY FLUID
Faeces

HBV

HBsAg

Infectivity

(-)

Bile,
pancreas

(-),

Saliva

(+)

(+)

replicate (+)
Percutan

Semen-

(+)

(+)

IV

Low

Low

No

vaginal fluid

Collostrum

HBV SERODIAGNOSIS
Acute HBV infection with recovery
Serologic course

Acute

symptoms

(6 months)

Total anti HBc

HBsAg

Progression to Chronic HBV infection

Serologic course

IgM anti
HBc

HBV DNA
Window p

Weeks after exposure

Anti
HBs

Chronic
(years)

HBsAg

IgM anti
HBc
HBV DNA

Weeks after exposure

DIAGNOSIS
ACUTE HBV
HBs HBe IgM IgG Anti Anti DNA
Ag Ag
HBc HBc HBs HBe
Initial

Window

Resolved

+/+

DIAGNOSIS
CHRONIC HBV
HBs HBe IgM IgG Anti Anti DNA
Ag
Ag
HBc HBc HBs HBe
Replicate
+
+
+
+
Non Repl

Flare up

+/-

PreCore

mutant

+
+

Superinfection
HVA, HVC, etc

Drugs, toxin
(acetaminophen
etc)

HBsAg (+)

Acute hepatitis

Acute HBV
HBsAg, IgM
antiHBc

Reactivation

chronic
HBV

Exacerbation
chronic HBV,

eAg conversion

Differential diagnosis HBV

HEPATITIS C VIRUS (HCV)

The silent killer

Intrafamilial 4.3%; sexual 5%

Vertical transmission 6% (2-11%)
Risk factors:
* maternal RNA titer, obstetric factor:
RNA (13 vs 6%),
* viremia
+/(8 vs 3%),
* Pervaginam/SC
(6 vs 0%)

Seroprevalence HCV in children

USA (Rosenthal P,2006)
. < 12 years : 0,2%
. 12-19 years : 0,4%
-- 240.000 children anti HCV (+)
----- perinatal transmission !!
-- prevention !!!-- education !!!

PATHOPHYSIOLOGY

Liver injury :
non cytopathic
immune response
Chronicity 85% - Th2 > Th1
Slow onset cirrhosis decade 3 4

In children:few

Exposure

(acute phase)

Chronic

Resolved
Stable

Cirrhosis

Slowly
progressive
Perinatal transmission: major-mild in first decade.
others :aggressive(cirrhosis)

HCC
Transplant
Death

Three generation anti-HCV antibody ELISA test

HCV genome
Structural

E1

E2

Non Structural

NS2

NS3

ELISA antibody test

NS4

NS5

Coding region for

antigen peptides used
in ELISA

1st generation

NS4

2nd generation

NS3, NS4

3rd generation

NS3, NS4

NS5

SEROLOGY
ACUTE HCV - RESOLVED
Anti
HVC

symptom

SEROLOGY
CHRONIC HCV
symptom
HVC RNA

HVC RNA

SGPT

SGPT
Normal
Months

Anti
HVC

Normal
Years

Months

Years

HEPATITIS B VIRUS
(HBV)

Major health social problems

Transmission at early age
Carrier rate
Complications
Quality of life at productive age -
Cutting chain of transmission
Prevention - Treatment

HBV

PREVENTIVE MEASURES
PREVENTION

Horizontal
Vertical
transmission
transmission

General measures
Specific measures

HBV PREVENTION

GENERAL MEASURES

HORIZONTAL
TRANSMISSION
Screening donor
Sterilization
instruments
Gloves medical
staff
Contact
microlesion !!

VERTICAL
TRANSMISSION
Screening mother
Multi discipline
management
Availability HBV
vaccine/HBIg

HBV VACCINATION
Cutting chain of transmission

Newborn, adolescent

In endemic area -
maternal infection
Early infection chronic
reservoir
HCC at any age
Provide protection
adolescent - risk

High risk adults

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

Eliminating HBV, decreasing HCC

The only vaccine against CANCER

HBV PREVENTION

SPECIFIC MEASURES
HORIZONTAL
TRANSMISSION
* Pre-exposure
Active immunization
* Post-exposure
Passive & Active
immunizations

VERTICAL
TRANSMISSION
* Passive & Active
immunization
12 hours - birth

RECOMBINANT
HBV - VACCINE
SCHEDULE:

3 x, intervals:
min 1 month (1st-2nd), min 2 months (2nd-3rd)
deltoid, antero-lateral thigh
PROTECTION ( 10 mIU/ml): min 12 ys
SEROLOGIC TEST: (-)
LAPSED IMMUNIZATION: proceed,
repetition (-)
BOOSTER (-)

SEROLOGIC TESTING

Not recommended for infants - children

PREVACCINATION
Consider :
High risk population
Adolescents
endemic area
Family members
HBV carriers
Health care staff

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

INFANTS BORN TO
HBsAg (+) MOTHERS

Vertical transmission
In utero
At labor
Perinatal
Serologic testing age: 9 months
If Anti HBs (+), HBsAg (-) Anti
HBs testing aged 3, 5, 10 years

VACCINE NONRESPONDERS

< 5% vaccinees persistent non-responders

Complete the 2nd series of 3 doses

Usual schedule
Retest 1 2 months after completion
Check HBsAg & HBeAg status
If exposed, treat as nonresponder
with postexposure prophylaxis

HEPATITIS C

Complicated
Mutation rate
No vaccination
Asymptomatic
Antiviral response : small study size!!
Screening !!!

HCV VACCINE
Still far from completion

Failure to develop a vaccine

Which is the neutralizing antibody

E2, CAP, NS3 peptide?

E2 highly mutational
No identified antigen peptide that
produces adequate immune response
PREVENTION is important

General HBV
SPECIFIC
Screening:
Identify new
Donor, children
cases
carrier mother,
PREVENTION: important!!!
baby HCV mom,
IVDU, close contact,
Vaccine (-) High rate of mutation , no identified antigen
sexual
behavior,
chronic
HCC,
peptidethat produces adequate
immunehep,
response
multi-transfused,
cirrhosis, ALT
medical staff ,
?
LTx recipient

HCV POST TRANSFUSSION

All donors

HBsAg
Screening
donor

HIV - risk

Anti HIV
SGPT/Anti HBc

Anti HVC
Years

Algorithm for diagnosis HCV in

infants at risk of perinatal infection
1. Mother:anti HCV and/or HCV RNA (+)
(-)

HCV RNA at (+)

2-3 months

Repeat
6-12 months

(+)

Refer

(-) 2X
Anti HCV
at12 -18mo
(-)

2. Refer at age 12 months

HCV RNA and anti HCV

HCV RNA (-)

anti HCV (-)
HCV RNA (+)

(+)

Follow-up annually
until negative

Refer

HCV RNA(-)
anti HCV(+ )
resolved/
maternal Ab if
< 18 morepeat
after 6 mo ---(-)

* Say no to alcohol smoke narcotics

* Avoid sharing needles, use gloves
* Avoid consuming any drugs if possible
* Be cautious in using several drugs
* Avoid contact with chemicals
* Healthy & balanced diet, avoid obesity
* Safe sex

FINAL MESSAGE

Get yourself vaccinated

Get your family vaccinated
Get your patients vaccinated
Get your community vaccinated
Spread the knowledge

Lets work hand in hand

to overcome the problem

Thank you