HEPATITIS

DRHARIFFADILLAHSpPD

Manycausesofhepatitis
Infectious

Bacterial

Parasitic

Viral

Noninfectious

Leptospirosis
Syphillis
Tuberculosis
Toxoplasmosis
Amebiasis
EpsteinBarr
HerpesSimplex
VaricellaZoster
Coxsackievirus
Rubella
YellowFever
Alcohol
Drugs

Viralagentsthatprimarilyor
exclusivelyinfecttheliver
HepatitisAvirus

Infectioushepatitis

HepatitisBvirus

Serumhepatitis

HepatitisCvirus

Parenterallytransmitted

HepatitisEvirus

Entericallytransmitted

HepatitisDvirus

CoinfectionwithHBV

HepatitisGvirus

Parenterallytransmitted

Viral Hepatitis - Historical

Perspective
Enterically
E
transmitted

Infectious A
Viral
hepatitis

NANB

Serum B D

Parenterally
C transmitted

F, G,
? other

Viral Hepatitis Overview

Type of Hepatitis

A
Source of
virus
Route of
transmission
Chronic
infection
Prevention

feces

fecal-oral
no

blood/
blood/
blood/
blood-derivedblood-derived blood-derived
body fluids body fluids body fluids

E
feces

percutaneouspercutaneous percutaneous fecal-oral

permucosal permucosal permucosal
yes

yes

yes

no

pre/postpre/post- blood donor

pre/post- ensure safe
exposure
exposure
screening;
exposure
drinking
immunization immunization risk behavior immunization;
water
modification risk behavior
modification

Initiallaboratoryevaluationof
jaundicedpatient
TESTPERFORMED

MEASUREMENT

Urinebilirubin

Conjugatedbilirubin

Serumbilirubin

Conjugatedandunconjugatedbilirubin

Alanineaminotransferase(ALT)

Hepatocellulardamage

Aspartateaminotransferase(AST)

Heptocellulardamage

Alkalinephosphatase

Intrahepaticorextrahepaticobstruction

Prothrombintime,partial
thromboplastintime,plateletcount,
bleeding

Clottingmechanism

Bloodcountwithbloodsmearexam

Redbloodcellmorphology,parasites,
atypicallymphocytes

HEPATITIS A VIRUS
RNAPicornavirus
Singleserotypeworldwide
Acutediseaseandasymptomaticinfection

Nochronicinfection
Protectiveantibodiesdevelopinresponseto
infectionconferslifelongimmunity

ACUTE HEPATITIS A CASE

DEFINITION FOR SURVEILLANCE
Clinicalcriteria
Anacuteillnesswith:
discreteonsetofsymptoms(e.g.fatigue,abdominalpain,lossof
appetite,intermittentnausea,vomiting),and
jaundiceorelevatedserumaminotransferaselevels
Laboratorycriteria
IgMantibodytohepatitisAvirus(antiHAV)positive
CaseClassification

Confirmed.Acasethatmeetstheclinicalcasedefinitionandislaboratory
confirmedoracasethatmeetstheclinicalcasedefinitionandoccursina
personwhohasanepidemiologiclinkwithapersonwhohaslaboratory
confirmedhepatitisA(i.e.,householdorsexualcontactwithaninfected
personduringthe1550daysbeforetheonsetofsymptoms).

HEPATITIS A - CLINICAL
FEATURES
Jaundice by

age group:
Rare complications:

<6 yrs
6-14 yrs
>14 yrs

<10%
40%-50%
70%-80%

Fulminant hepatitis
Cholestatic hepatitis
Relapsing hepatitis

Incubation period:

Average 30 days
Range 15-50 days

EVENTS IN HEPATITIS A VIRUS INFECTION

Clinical illness

Infection

ALT

Response

IgM

IgG

Viremia

HAV in stool

Week

10

11

12

13

CONCENTRATION OF HEPATITIS A VIRUS

IN VARIOUS BODY FLUIDS
Body Fluids

Feces
Serum
Saliva
Urine

100

102

104

106

Infectious Doses per mL

Source:

Viral Hepatitis and Liver Disease 1984;9-22

J Infect Dis 1989;160:887-890

108

1010

GLOBAL PATTERNS OF
HEPATITIS A VIRUS TRANSMISSION
Disease
Rate

Peak Age
of
Infection

High

Low to high

Early childhood

Person to person;
outbreaks uncommon

Moderate

High

Late childhood/
young adults

Person to person;
food and waterborne
outbreaks

Low

Young adults

Person to person;
food and waterborne
outbreaks
Travelers; outbreaks
uncommon

Endemicity

Low
Very low

Very low

Adults

Transmission
Patterns

GEOGRAPHIC DISTRIBUTION OF
HEPATITIS A VIRUS INFECTION

HEPATITIS A VIRUS TRANSMISSION

Closepersonalcontact
(e.g.,householdcontact,sexcontact,child
daycarecenters)
Contaminatedfood,water
(e.g.,infectedfoodhandlers)
Bloodexposure(rare)
(e.g.,injectiondruguse,rarelyby
transfusion)

PREVENTING HEPATITIS A
Hygiene(e.g.,handwashing)
Sanitation(e.g.,cleanwatersources)
HepatitisAvaccine(preexposure)
Immuneglobulin(preandpostexposure)

HEPATITIS A VACCINES
Highly immunogenic
97%-100% of children, adolescents, and adults

have protective levels of antibody within 1

month of receiving first dose; essentially
100% have protective levels after second dose
Highly efficacious
In published studies, 94%-100% of children

protected against clinical hepatitis A after

equivalent of one dose

HEPATITIS A VACCINE EFFICACY

STUDIES
Vaccine Efficacy
Site/
Age Group

HAVRIX
(GSK)
2 doses
360 EL.U.

Thailand

38,157

VAQTA
(Merck)
1 dose
25 units

New York

Vaccine

1-16 yrs

2-16 yrs

JAMA 1994;271:1363-4; N Engl J Med 1992;327:453-7

(95 % Cl)

94%
(79%-99%)

1,037

100%
(85%-100%)

SAFETY OF HEPATITIS A VACCINE

Mostcommonsideeffects
Soreness/tendernessatinjectionsite50%
Headache15%
Malaise7%
Nosevereadversereactionsattributedtovaccine
Safetyinpregnancynotdeterminedrisklikelylow
Contraindicationssevereadversereactiontopreviousdoseorallergytoavaccinecomponent
Nospecialprecautionsfor
immunocompromisedpersons

DURATION OF PROTECTION AFTER

HEPATITIS A VACCINATION
Persistenceofantibody

Atleast58yearsamongadultsandchildren

Efficacy

Nocasesinvaccinatedchildrenat56yearsoffollow
up

Mathematicalmodelsofantibodydeclinesuggest
protectiveantibodylevelspersistforatleast20
years
Othermechanisms,suchascellularmemory,
maycontribute

COMBINED HEPATITIS A
HEPATITIS B VACCINE
ApprovedbytheFDAinUnitedStatesforpersons>18years
old
Contains720EL.U.hepatitisAantigenand
20g.HBsAg
Vaccinationschedule:0,1,6months
Immunogenicitysimilartosingleantigenvaccinesgiven
separately
Canbeusedinpersons>18yearsoldwhoneedvaccination
againstbothhepatitisAandB
Formulationforchildrenavailableinmanyothercountries

HEPATITIS A PREVENTION
IMMUNE GLOBULIN
Preexposure

travelerstointermediateandhigh
HAVendemicregions

Postexposure(within14days)

Routine
householdandotherintimatecontacts
Selectedsituations
institutions(e.g.,daycarecenters)
commonsourceexposure(e.g.,
foodpreparedbyinfectedfoodhandler)

HepatitisBVirus
HBV

HBVnomenclature

HBV:hepatitisBvirus
HBsAg:hepatitisBvirussurfaceantigen
HBcAg:hepatitisBviruscoreantigen
HBeAg:penandareplikasi
AntiHbe:replikasirendah

HBVEpidemiology
Horizontaltransmission
Persontopersonspread
Parenteral
Sexual

Verticaltransmission
Chronicallyinfectedmothertochild
Atbirthorviabreastmilk

HBVPathology
Portalofentry
Percutaneousismostefficient
Sexualorperinatalisless
efficientbutmajorsource

Intobloodstreamandtoliver
Hepatocytes
Littlecytopathology
Immunepathology

HBVEpidemiology

HBVClinicalSyndromes
ACUTEINFECTION
Incubationphase:long
Prodromalphase:insidious
Flulike:malaise,fatigue,anorexia,nausea,abdominaldiscomfort,
chills

Ictericphase:liverdamage:jaundice,darkurine,pale
stools
Recovery:declineinfever;renewedappetite

HBVDiagnosis
Clinical
Symptoms
LookslikeHAV

HBVDiagnosis
Laboratory
Liverenzymes
Serology
HBeAg,HBcAg,virus:activeinfection
AntiHBcIgM:acuteactiveinfection
AntiHBeIgG:acuteinfection

HBVTreatment
Supportive
Interferon:manysideeffects
Otherantiviraldrugs
Lamivudine:duringviral
infection
Famciclovir:reversetranscriptase
inhibitor

HBVComplications
Fulminatehepatitis
Chronichepatitis
5%10%ofHBVinfections
10%oftheseprogresstocirrhosis/liverfailure
Athigherriskforfulminanthepatitis

HBVComplications
ChronicHBsAgantigenemia

Postviral;asymptomaticcarrier
state;HBsAgonly

Chronicpersistenthepatitis(CPH)

Postviral;elevatedtransaminase;no
progressiontoliverdisease

Chronicactivehepatitis(CAH)

Postviral;progressestoliver
disease

Chroniclobularhepatitis(CLH)

Postviral;noprogressiontoliver
disease;elevatedtransaminase
levels

Livercirrhosis
Hepatocellularcarcinoma

2030yearsofpersistentHBV
infectionleadingtoliverinjury

HBVPrevention
Screenbloodproducts
Sterilizationofneedles,etc.
Avoidingintimatecontact,e.g.,
householdorsexualcontacts
Vaccination
Subunitvaccines
HBsAg