VIRAL HEPATITIS

Nining Sri WuryaningsihBagian Patologi Klinik FK UNS

• Largest Organ

• Main functions: 1. Metabolite regulation in blood 2. Detoxication

• RegenerateRegenerate if if damageddamaged

Old Old ErythrocytesErythrocytesSpleen

Urobi-Urobi-linogelinogenn

Small amount –entero-hepatic circulation

StercobiliStercobilinene

HEPATITISHEPATITIS• Inflammation & Inflammation & necrosisnecrosis• Infection & nonInfection & non

Conj. Conj. bilirubibilirubinn

Unconj Unconj bilirubinbilirubin

PROBLEMSPROBLEMS Medico-psycho-sosio-economicsMedico-psycho-sosio-economics

Morbidity - mortality Epidemiology – endemic area

carrier rate - transmission rate Therapeutics ? Quality of life?

PreventionPrevention - !!! - !!!

OBJECTIVES:OBJECTIVES:

PRINCIPLES - MANAGEMENTPRINCIPLES - MANAGEMENT

Epidemiology, virology, patophysiology: Early DiagnosisEarly Diagnosis Supportive & monitoring Early detection: fulminant, chronicity Prevention of spreadingPrevention of spreading Antivirus treatment

HEPATITIS A - GHEPATITIS A - G

HAVHAV HBVHBV HCVHCV HGVHGVVirusVirus Picorna Hepadn

aFlavi Flavi

IncubatioIncubationn

15-40 days

50-160days

1-5 months

? 2 weeks

OnsetOnset Acute Subclinic Subclinic Acute/subOral-fecalOral-fecalParenteraParenterall

(++)Rare

(-)(++)

(-)(++)

(-)(++)

ChronicitChronicityy

(-) (+) (+) (+)

HBV Carriers > 350 jutaHBV Carriers > 350 juta 78% in 78% in AsiaAsia Indonesia: Moderate – high endemic Indonesia: Moderate – high endemic (3-(3-20%)20%)

HBsAg prevalence> 8% - High2-7%: Moderate< 2% - Low

Transmission

Early Infection chronicchronic - -

95%95% HCC – HCC –

childrenchildren

! Prevention: ! Prevention: Infection control & immunization Infection control & immunization ASAPASAP

Maternal screeningMaternal screening

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

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

Newborn of – HBV mothers --(2,1-6,7%)

Transfusion Transplantation,diallysis,accupunctu

reIntravenousDrug users,Tattoo,ear

piercing

Medics/ paramedics

Family members HBV carriers

Multiplesexual

partners/homosex

uals

Prone to injury:army;P

risoners, institutional,

PARENTERALLYPARENTERALLYTRANSMITTEDTRANSMITTED

MATERNAL TRANSMISSION MATERNAL TRANSMISSION Major route - in endemic areaMajor route - in endemic area

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

TIMINGTIMING ACUTE HVBACUTE HVB CHRONIC HVBCHRONIC HVB1st Trimester 3rd Trimester At birthAt birth11stst five years five years

10%60-70%

10%31 – 90%31 – 90%80-85%

50%

HORIZONTAL TRANSMISSION vsHORIZONTAL TRANSMISSION vsBODY FLUID BODY FLUID

HBVHBV HBsAgHBsAg InfectivityInfectivityFaeces (-) Bile,

pancreas(-),

replicate (+)

Saliva (+) (+) PercutanSemen-vaginal fluid

(+) (+) IV

Collostrum

Low Low No

HBV SERODIAGNOSIS HBV SERODIAGNOSIS

Acute HBV infection with recovery Serologic course

Progression to Chronic HBV infectionSerologic course

Weeks after exposure Weeks after exposure

IgM anti HBc

AntiAntiHBsHBsHBsAgHBsAg

HBV DNAHBV DNA

IgM IgM anti anti HBcHBc

symptoms

Acute(6 months)

Chronic(years)

HBsAgHBsAgTotal anti HBcTotal anti HBc

Window pWindow pHBV DNAHBV DNA

DIAGNOSISDIAGNOSIS ACUTE HBV ACUTE HBV

HBsHBsAgAg

HBeHBeAgAg

IgMIgMHBcHBc

IgGIgGHBcHBc

AntiAntiHBsHBs

AntiAntiHBeHBe

DNADNA

Initial ++ ++ ++ -- ++

Window

-- ++ +/-+/-

Resolved

-- ++ ++ ++ --

DIAGNOSISDIAGNOSIS CHRONIC HBV CHRONIC HBV

HBsHBsAgAg

HBeHBeAgAg

IgMIgMHBcHBc

IgGIgGHBcHBc

AntiAntiHBsHBs

AntiAntiHBeHBe

DNADNA

ReplicatReplicatee

++ ++ ++ -- ++

Non ReplNon Repl ++ ++ ++ --

Flare upFlare up ++ +/-+/- ++ ++ -- ++

PreCorePreCoremutantmutant

++ -- ++ -- ++ ++

Differential diagnosis HBVDifferential diagnosis HBV

Superinfection HVA, HVC, etc

Drugs, toxin (acetaminoph

enetc)

HBsAg (+) HBsAg (+) Acute Acute

hepatitishepatitis

Acute HBVAcute HBVHBsAg, IgM

antiHBc

Reactivation chronic

HBV

Exacerbation chronic HBV,

eAg conversion

HEPATITIS C VIRUS (HCV)HEPATITIS C VIRUS (HCV)The silent killerThe 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 childrenUSA (Rosenthal P,2006). < 12 years : 0,2%. 12-19 years : 0,4% -- ± 240.000 children anti HCV (+)

----- perinatal transmission !! -- prevention !!!-- education !!!

PATHOPHYSIOLOGYPATHOPHYSIOLOGY

Liver injury : non cytopathicimmune response

Chronicity 85% - Th2 > Th1 Slow onset – cirrhosis decade 3 – 4

ResolvResolveded

StableStable

Slowly Slowly progressiveprogressive

HCCHCCTransplantTransplantDeathDeath

ExposureExposure(acute phase)(acute phase)

ChronChronicic

CirrhosisCirrhosis

In children:fewIn children:few

Perinatal transmission: major-mild in first decade.Perinatal transmission: major-mild in first decade.

others :aggressive(cirrhosis)others :aggressive(cirrhosis)

ELISA antibody ELISA antibody testtest

11stst generationgeneration2nd 2nd generationgeneration33rdrd generationgeneration

Coding region for Coding region for antigen peptides antigen peptides used in ELISAused in ELISA

HCV HCV genomegenomeStructuralStructural Non StructuralNon Structural

NS2NS2 NS3 NS3 NS4NS4 NS5NS5CC E1E1 E2E2

NS4NS4

CC NS3, NS4NS3, NS4

CC NS3, NS4NS3, NS4 NS5NS5

Three generation anti-HCV antibody ELISA Three generation anti-HCV antibody ELISA testtest

SEROLOGY SEROLOGY ACUTE HCV - RESOLVEDACUTE HCV - RESOLVED

Anti HVC

SGPSGPTT

HVC HVC RNARNA

symptomsymptom

Normal

Months

Years

MonthMonthss

YearsYears

SGPT

SEROLOGY SEROLOGY CHRONIC HCVCHRONIC HCVsymptosymptommHVC RNAHVC RNA

Anti HVC

Normal

HEPATITIS B VIRUSHEPATITIS B VIRUS(HBV)(HBV) Major health – social problems

Transmission at early age Carrier rate Complications Quality of life at productive age -

Cutting chain of transmissionPrevention - Treatment

HBVPREVENTIVE MEASURES

PREVENTION

Horizontal Verticaltransmission transmission

General measures Specific measures

HBVHBV PREVENTION PREVENTIONGENERAL MEASURESGENERAL MEASURES

HORIZONTAL TRANSMISSION

Screening – donor Sterilization –

instruments Gloves – medical

staff Contact –

microlesion !!

VERTICAL TRANSMISSION

Screening mother Multi discipline

management Availability – HBV

vaccine/HBIg

HBV VACCINATIONHBV VACCINATION Cutting chain of Cutting chain of transmissiontransmission

Newborn, adolescentNewborn, adolescent In endemic area -

maternal infection Early infection chronic

– reservoir HCC at any age Provide protection –

adolescent - risk

High risk adultsHigh risk adults Dialysis, transfused IVDU, homosex,

active heterosexuals Household contacts

of HBV carriers Health care worker

Eliminating HBVEliminating HBV, decreasing HCC, decreasing HCC The “only” vaccine against The “only” vaccine against CANCERCANCER

HBV HBV PREVENTIONPREVENTION SPECIFICSPECIFIC MEASURESMEASURES

HORIZONTAL TRANSMISSION* Pre-exposure

Active immunization* Post-exposure

Passive & Active immunizations

VERTICAL TRANSMISSION

* Passive & Active immunization 12 hours - birth

RECOMBINANT RECOMBINANT HBV - VACCINEHBV - 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

PREVACCINATIONPREVACCINATIONConsider :High risk population◘ Adolescents –

endemic area◘ Family members –

HBV carriers◘ Health care staff

POST-POST-VACCINATIONVACCINATION

Infants - HBsAg (+) mothers

High risk newborns Immunodeficient Dialysis patients Health care

workers

INFANTS BORN TO INFANTS BORN TO HBsAg (+) MOTHERSHBsAg (+) MOTHERS■ Vertical transmission

In uteroAt labor Perinatal

■ Serologic testing – age: 9 months■ If Anti HBs (+), HBsAg (-) Anti

HBs testing aged 3, 5, 10 years

VACCINE NONRESPONDERSVACCINE NONRESPONDERS < 5% vaccinees – persistent non-< 5% vaccinees – persistent non-respondersresponders

◘ 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 CHEPATITIS C■ Complicated

Mutation rate No vaccinationAsymptomaticAntiviral response : small study

size!!

■ Screening !!!

HCV VACCINEHCV VACCINEStill far from completionStill far from completion

Failure to develop a vaccineFailure to develop a vaccine Which is the neutralizing antibody E2, CAP, NS3 peptide? E2 – highly mutational No identified antigen peptide – that No identified antigen peptide – that

produces adequate immune responseproduces adequate immune responsePREVENTION is important

PREVENTIONPREVENTION: important!!!: important!!! Vaccine (-)Vaccine (-) High rate of mutation , no identified High rate of mutation , no identified antigen antigen peptide- that produces adequate peptide- that produces adequate immune response–immune response–

General HBVScreening:Donor, children carrier mother,IVDU, close contact,sexual behavior, multi-transfused, medical staff , LTx recipient

SPECIFICSPECIFIC Identify new cases baby – HCV mom,

chronic hep, HCC, cirrhosis, ALT – ?

HCV POST TRANSFUSSIONHCV POST TRANSFUSSIONAll donors

HBsAgHBsAg

Anti HVC

SGPT/Anti HBcAnti HIV

Screening Screening donordonor

HIV - riskHIV - risk

YearsYears

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 mo—

repeat (+) at12 -18mo after 6 mo ---(-) until negative Refer (-)

* Say no to* Say no to alcohol – smoke – narcotics * Avoid sharing needles, use gloves* Avoid consuming any drugs if possible* Avoid consuming any drugs if possible * Be cautious in using several drugs* Avoid contact with chemicals* Healthy & balanced diet, avoid obesityavoid obesity* Safe sex* Safe sex

FINAL MESSAGEFINAL MESSAGE Get yourself vaccinated Get your family vaccinated Get your patients vaccinated Get your community vaccinated Spread the knowledge

Let’s work – hand in hand to overcome the problem

Thank you