VIRAL HEPATITIS

Nining Sri Wuryaningsih

Bagian Patologi Klinik FK UNS
 Largest Organ Spleen Old
Erythrocytes

Main functions: Unconj Small amount

1. Metabolite bilirubin entero-hepatic
regulation circulation

in blood Conj.
2. Detoxication bilirubin

Urobi-
Regenerate if linogen
damaged

HEPATITIS
Inflammation &
necrosis Stercobiline
Infection & non
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 50-160 1-5 ? 2 weeks

days days months
Onset Acute 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
> 8% - High
2-7%: Moderate
Early Infection HBsAg prevalence
< 2% - Low

chronic - 95%
 Transfusion Newborn of
Transplantation,dial HBV mothers --
lysis,accupuncture (2,1-6,7%)

Intravenous
Medics/
paramedics Drug users,
Family members Tattoo,ear
HBV carriers piercing
Multiple
sexual Prone to
partners/h PARENTERALLY injury:army;Pris
omosexual oners,
s
TRANSMITTED
institutional,
 MATERNAL TRANSMISSION
Major route - in endemic area

TIMING ACUTE HVB CHRONIC HVB

1st Trimester 10% 10%
3rd Trimester 60-70% 31 90%
At birth 80-85%
1st five years 50%
Risk: HBeAg (-) 22 76%: Anti HBe (+)
fulminant !!!
 HORIZONTAL TRANSMISSION vs
BODY FLUID
HBV HBsAg Infectivity
Faeces (-) Bile, (-),
pancreas replicate (+)
Saliva (+) (+) Percutan

Semen- (+) (+) IV

vaginal fluid
Collostrum Low Low No
 HBV SERODIAGNOSIS

Acute HBV infection with recovery Progression to Chronic HBV infection

Serologic course Serologic course
Acute Chronic
symptoms (6 months) (years)

HBsAg
Total anti HBc

IgM anti Anti

IgM anti
HBsAg HBc HBs
HBc
HBV DNA
HBV DNA
Window p

Weeks after exposure 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
 Drugs, toxin
Superinfection (acetaminophen
HVA, HVC, etc etc)

HBsAg (+)
Acute hepatitis

Acute HBV Reactivation Exacerbation

HBsAg, IgM chronic chronic HBV,
antiHBc 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)

Resolved Chronic

Stable Cirrhosis

Slowly HCC
progressive Transplant
Death
Perinatal transmission: major-mild in first decade.
others :aggressive(cirrhosis)
Three generation anti-HCV antibody ELISA test
HCV genome
Structural Non Structural

C E1 E2 NS2 NS3 NS4 NS5

ELISA antibody test Coding region for

antigen peptides used
1st generation NS4 in ELISA

2nd generation C NS3, NS4

3rd generation C NS3, NS4 NS5

 SEROLOGY SEROLOGY
ACUTE HCV - RESOLVED CHRONIC HCV
Anti Anti
symptom HVC symptom HVC

HVC RNA HVC RNA

SGPT SGPT

Normal Normal

Months 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 VERTICAL
TRANSMISSION TRANSMISSION
Screening donor Screening mother
Sterilization Multi discipline
instruments management
Gloves medical
staff
Availability HBV
vaccine/HBIg
Contact
microlesion !!
 HBV VACCINATION
Cutting chain of transmission
Newborn, adolescent High risk adults
In endemic area -
maternal infection
Dialysis, transfused
Early infection chronic IVDU, homosex,
reservoir active heterosexuals
HCC at any age
Provide protection
Household contacts of
adolescent - risk HBV carriers
Health care worker

Eliminating HBV, decreasing HCC

The only vaccine against CANCER
HBV PREVENTION
SPECIFIC MEASURES
HORIZONTAL VERTICAL
TRANSMISSION TRANSMISSION
* Pre-exposure * Passive & Active
Active immunization immunization
* Post-exposure 12 hours - birth
Passive & Active
immunizations
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 POST-
Consider : VACCINATION
Infants - HBsAg (+)
High risk population
mothers
Adolescents
High risk newborns
endemic area
Immunodeficient
Family members
Dialysis patients
HBV carriers
Health care
Health care staff
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
Screening:
SPECIFIC
Identify new
Donor, children
carrier mother, cases
PREVENTION: important!!!
IVDU, close contact, baby HCV mom,
Vaccine (-) High rate of mutation , no identified antigen
sexual behavior,
peptide- chronic
that produces adequate immunehep, HCC,
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 (+) 2. Refer at age 12 months

(-) HCV RNA at (+) HCV RNA and anti HCV

2-3 months

(+)
Repeat Refer HCV RNA (-) HCV RNA(-)
6-12 months anti HCV (-) anti HCV(+ )

(-) 2X HCV RNA (+) resolved/

maternal Ab if
Anti HCV Follow-up annually < 18 morepeat
(+)
at12 -18mo after 6 mo ---(-)
until negative Refer

(-)
* 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