hepatitisvirus

8/19/2019 hepatitisvirus

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Hepatitis virus


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Overview of Hepatitis Virus

Virus Virus group Nucleicacid Mode of infection Severity(chronicity)

HAV Enterovirus7(heptovirus)

!NA "ecal#oral $(acute)

H%V hepadnavirus &NA 'ercutaneous

'erucosal

$$(chronic)

H*V "lavivirus !NA %lood(transfusion#associated)

$ (chronic)

H&V %#dependentsall virus

!NA +lood $ (chronic)

HEV *alicivirus !NA "ecal#oral $(acute)

H,V - !NA %lood -


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Viral Hepatitis - Overview

A B C D ESource of virus

feces blood/blood-derived

body fluids

blood/blood-derived

body fluids

blood/blood-derived

body fluids

feces

Route of transmission

fecal-oral percutaneouspermucosal

percutaneouspermucosal

percutaneouspermucosal

fecal-oral

Chronicinfection

no yes yes yes no

Prevention pre/post-exposure

immunization

pre/post-exposure

immunization

blood donor screening;

risk behavior modification

pre/post-exposure

immunization;risk behavior modification

ensure safedrinking

ater

Type of Hepatitis


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Huan cytoegalovirus

Epstein#%arr virus

Herpes siple. virus /ellow fever virus

!u+ella0


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Hepatitis A virus


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Structure

Small# non$

envelope"

icosa%e"ral

particle#

&' nm in

"iameter

ss!NA


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!eplication

1nli2e other picornaviruses3 however3 HAV is notcytolytic and is released +y e.ocytosis0

4a+oratory isolates of HAV have +een adapted to

growth in priary and continuous on2ey 2idney celllines3 +ut clinical isolates are very difficult to grow in

cell culture(


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!esistance

Stable toaci" at p) *

Solvents+et%er#c%loroform,

"etergents

salt-ater#groun"-ater+mont%s,

"rying+stable,

temperature

. -ee/s℃

01 for *2minutes stable℃

13 for &2minutes partial inactivation℃


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!esistance

Inactivate" by

c%lorine treatment of "rin/ing -ater

formalin+2(*04#*' #'&%ours,℃

acetic aci"+&4#.%ours,

B$propiolactone丙内酯 +2(&04#3%ours,

Ultraviolet ra"iation+&567㎝ &7min,


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Hepatitis A Virus Transmission

Virus can +e transitted via fecal#oral routeingestion of containated food and water can

cause infection

HAV in shellfish is fro sewage#containated

water

Virus can +e transitted +y food handlers3 day#

care wor2ers3 and children0


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Concentration of Hepatitis A Virusin Various Body Fluids

Source! "iral #epatitis and $iver %isease &'();'-**

+ ,nfect %is &'(';&.!((-('.

Feces

Serum

Saliva

Urine

B o d y

F l u i d

Infectious Doses perml

100 102 104 10 10! 1010


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Geographic Distribution of HAVInfection

Anti"HA# $revalence

Hi%&

'nterme(iate

)o*

#ery )o*


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Age-specic Mortality Due toHepatitis A

Age groupyears!

"ase-Fatalityper #$$$!

! "#$

!-%& %#'%!-() %#'

"$-&) "#*+&) %,#!

otal %

Source! "iral #epatitis Surveillance Program0 &'(1-&'('


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Hepatitis A - "linicalFeatures

5ncu+ation period

Average 6 days

!ange 89#9 days

:aundice +yage group

;< yrs ;8=

yrs >=#9=

?8> yrs 7=#@=


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Hepatitis A - Clinical Features

Milder disease than Hepatitis % asyptoatic infections are very coon3

especially in children0 Adults3 especially pregnant woen3 ay develop

ore severe disease no chronic for of the disease0

Complications:"ulinant hepatitis is rare 08= of cases


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Pathog n sis


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'athogenesis of HAV

HAV replicates slowly in the liver without

producing apparent cytopathological effects

(*E's)0 5n the a+sence of cytolysis3 the virus

readily esta+lishes a persistent infection0 :aundice3 resulting fro daage to the liver

Anti+ody is detected and cell#ediated iune

responses to the virus


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"or e.aple

An epideic of HAV that occurred in Shanghai3 *hina3

in 8B@@ in which 63 people were infected with the

virus resulted fro eating Anadara subcrenata

o+tained fro a polluted river 0


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Cie course of HAV infection


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5unity

Anti+ody protection against reinfection is lifelong


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4a+oratory &iagnosis

Viral particles in the stool3 +y electron icroscopy

Specific 5gM in seru

'*! HAV#specific seDuences in stool


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Creatent3 'revention and *ontrol

'rophyla.is with iune seru glo+ulin given +efore

or early in the incu+ation period

A 2illed HAV vaccine has +een approved and isavaila+le for use in children and adults at high ris2 for

infection0

A live HAV vaccine has +een developed in *hina0


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Hepatitis B virus


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Intro"uction

appro.iately 69 illion people are infected

glo+ally with H%V0


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Structure

Sall3 enveloped &NA

Che genoe a sall3 circular3 partly dou+le#stranded

&NA of 6 +ase

Although a &NA virus3 it encodes a reverse transcriptase

and replicates through an !NA interediate0


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Structure

&ane particle3 is > n in

diaeter0

!esist to treatent with ether3 a

low pH3 freeing3 and oderate

heating0 Chis helps transission

fro one person to another0


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Decoy !articles

)BsAg$containing particlesare release" into t%e serum of

infecte" people an"

outnumber t%e actual virions(

Sp%erical or filamentous

T%ey are immunogenic an"

-ere processe" into t%e first

commercial vaccine against)B8(


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Structure H%cAg H%sAg H%eAg

89#9n>n


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FFn

>n

@n

H%sAg

H%cAg

H%eAg

&NA


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H%V has a very defined tropis for the liver0 5ts sall genoe also necessitates econoy3 as

illustrated +y the pattern of its transcription and

translation0

5n addition3 H%V replicates through an !NA

interediate and produces and release antigenic

decoy particles0

!eplication


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!eplication

Che entire genoe can also +e integrated into the host

cell chroatin0

H%sAg3 +ut not other proteins3 can often +e detected in

the cytoplas of cells containing integrated H%V &NA0 Che significance of the integrated &NA in the replication

of the virus is not 2nown3 +ut integrated viral &NA has

+een found in hepatocellular carcinoas0


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High (?@=) >9= of glo+al population

G lifetie ris2 of infection ?6= of glo+al population

G lifetie ris2 of infection =#


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)ig%$ris/ groups for )B8infection

'eople fro endeic regions %a+ies of others with chronic H%V 5ntravenous drug a+users 'eople with ultiple se. partners Heophiliacs and other patients reDuiting +lood

and +lood product treatents Health care personnel who have contact with +lood

!esidents and staff e+ers of institutions for theentally retarded

"oncentration of Hepatitis B


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"oncentration of Hepatitis B

Virus

in Various Body Fluids

High Blood ,Serum, Wound exudates

Moderate Semen, vaginal and menstrualsecretions, Saliva, amniotic fuid

Low/NotDetectale

!rine , "eces, Sweat , #ears ,Breast mil$


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6%at "etermines t%e "evelopment of c%ronic vs

acute infection

Age (chronic infections decrease with increasing age)

Se.

Syndroe Males "eales

*hronic 5nfection 809 8 *irrhosis 6 8

'H* < 8

!oute of infection (oralse.ual infections give rise to

less chronic cases than seru infection

Hepatitis B - "linical


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Hepatitis B "linicalFeatures

. /ncubation period0 Average '$-)$days

1ange &!-%*$ days

. Clinical illness 23aundice40 ! yrs5 %$6>! yrs5 "$6-!$6

. Acute case-fatality rate0 $#!6-%6

. C7ronic infection0 ! yrs5 "$6-)$6

>! yrs5 (6-%$6. 8re9ature 9ortality fro9

c7ronic liver disease0 %!6-(!6

% t f H titi B Vi I f ti


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%utcome of Hepatitis B Virus Infectionby Age at Infection

Symptomatic 'nfection

C&ronic 'nfection

A%e at 'nfection

C & r o n i c ' n f e c t i o n + ,

-

S y m p t o m

a t i c ' n f e c t i o n

+ , -

Birt& 1" mont&s ."12 mont&s 1"4 years /l(er C&il(ren

an( A(ults

0

20

40

0

!0

100100

!0

0

40

20

0


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'athogenesis(8)

Che virus starts to replicate within 6 days of its

acDuisition3

Syptos ay not +e o+served for >9 days oflonger3 depending on the infectious dose3 the

route of infection3 and the person0


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h i ()


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'athogenesis()

Hypoiune response0

5"NI3H4A#5IJ*C4I(An insufficient C#cell response )

*ell ediated iunopathogenic daage0

*C4 Jacute hepatitischronic hepatitis

! % i +*,


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!at%ogenesis +*,

5une cople.es fored +etween H%sAg and anti#

H%s contri+ute to the developent of hypersensitivity

reactions3 leading to pro+les such as vasculitis血管炎 3

arthralgia关节痛 3 rash3 and renal daage0

' h i (>)


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'athogenesis(>)

'athogenic daage caused +y autoiunity

liver specific protein(4S')

Viral variation H%eAg


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Clinical Syn"romes


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Ma:or

eterminants of

acute an" c%ronic)B8 infection


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Acute Infection

Symptoms of Acute Infection


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Symptoms of Acute Infection


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T%e serological events associate" -it% t%e typical course of acu


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)B8 "isease


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&ypical 'erologic "ourseAcute Hepatitis B Virus /nfection wit7


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Acute Hepatitis B Virus /nfection wit71ecovery

(ee)s after

&iter

Symptoms

HBeA% anti"HBe

Total anti"HBc

'% anti"HBc anti"HBsHBsA%

0 4 ! 12 1 20 24 2! 2 2 100


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Development of t%e c%ronic )B8 carrier state


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p


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!rimary )epatocellular Carcinoma


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y p

T%e 6)O estimates t%at


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=ab( Diagnosis

T%e initial "iagnosis of %epatitis can be ma"e ont%e basis of t%e clinical symptoms an" t%e

presence of liver en;ymes in t%e bloo"(

T%e serology of infection "escribes t%e course

an" t%e nature of t%e "isease( Acute an" c%ronic )B8 infect( Can be

"istinguis%e" by t%e presence of )BsAg an"

)BeAg in t%e serum an" t%e pattern of Ab to t%ein"ivi"ual )B8 antigens(

Diagnosis


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Diagnosis

During t%e symptomatic p%ase of infection#

"etection of antibo"ies to )BeAg an" )BsAg is

obscure" because t%e antibo"y is comple>e"

-it% antigen in t%e serum( T%e best -ay to "iagnose a recent acute

infection# especially "uring t%e perio" -%en

neit%er )BsAg nor anti$)Bs can be "etecte"# is

to measure IgM anti$)Bc(


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Diagnosis


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g

Detection of serum )B8DNA nucleic

%ybri"i;ation? !CR(

Detection of viral DNA polymerase(

Treatment


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Interferon$alp%a may be effective for treating

a c%ronic )B8 infection(

)epatitis B immune globulin may be

a"ministere" -it%in a -ee/ of e>posure an" tne-born infants of )BsAg$positive mot%ers(

:li9ination of Hepatitis B Virus


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. 8revent c7ronic HBV /nfection

. 8revent c7ronic liver disease

. 8revent pri9ary 7epatocellularcarcino9a

. 8revent acute sy9pto9atic HBVinfection

rans9ission

Objectives

:li9ination of Hepatitis B Virusrans9ission


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. 8revent perinatal围产期的 HBVtrans9ission

. 1outine vaccination of all infants

. Vaccination of c7ildren in 7ig7-risk groups

. Vaccination of adolescents

; all unvaccinated c7ildren at %%-%( yearsof age

G K7ig7-riskL adolescents at all ages

. Vaccination of adults in 7ig7-risk groups

rans9issionStrategy

病毒抗原抗体系统检测结果分析


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H%sAg H%eAg 抗# H%s 抗# H%e 抗# H%c 结果分析

＋－－－－H%V

感染或无症状携带

者

＋＋－－－急性或慢性乙型肝炎

或无症状携带者

＋＋－－＋急性或慢性乙型肝炎!"染性#K$%&L'

＋－－＋＋急性感染 ( ) * +!K,%&L'

－－＋＋＋ -.感染*+/

－－＋＋－ -.感染*+/

－－－－＋ -.感染或K

01/L

－－＋－－ -.感染或23456


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)epatitis C 8irus)epatitis C 8irus

5ntroduction


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T%e ma:or cause of parenterally transmitte"

non A non B %epatitis( It elu"e" i"entification

for many years( In 3@


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pp

Incubation perio"Incubation perio" Average 1$' -ee/sAverage 1$' -ee/s

Range &$&1 -ee/sRange &$&1 -ee/s

Acute illness +:aun"ice,Acute illness +:aun"ice, Mil" +Mil" +&24,&24,

Case fatality rateCase fatality rate =o-=o-

C%ronic infectionC%ronic infection '04$,'24 +most as>,

Cirr%osisCirr%osis 324$&24324$&24

Mortality from C=DMortality from C=D 34$0434$04(chronic liver disease )

Common characteristics


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!utative Cogavirus relate" to t%e lavi an"!esti viruses(T%us probably envelope"(

)as a ssRNA genome

Does not gro- in cell culture# but can infect

C%impan;ees


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Transmission


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Bloo" transfusions# bloo" pro"ucts

organ "onation

Intravenous "rug abusers

community acuire" mec%anism unclear(

8ertical transmission

se>ual intercourse

Epi"emiology


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Causes a mil"er form of acute %epatitis t%an

"oes %epatitis B

But 024 in"ivi"uals "evelop c%ronic infection#

follo-ing e>posure( Inci"ence en"emic -orl"$-i"e? %ig% inci"ence

in Fapan# Italy an" Spain

Clinical syn"romes


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)C8 can cause acute infections but is more

li/ely to establis% c%ronic infections(

8iremia

C%ronic persistent %epatitis C%ronic active %epatiti-

Cirr%osis

=iver failure

C%ronic )epatitis Cactors !romoting !rogression or Severity


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actors !romoting !rogression or Severity

Increase" alco%ol inta/e

Age G .2 years at time of infection

)I8 co$infection Ot%er

G Male gen"er G Ot%er co$infections +e(g(# )B8,

Serologic !attern of Acute )C8 Infection-it% Recovery


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Symptoms H7$

Time after E>posure

T i t e r

anti$)C8

A=T

Normal

2 3 & * . 0 1 3 & * .earsMont%s

)C8 RNA

Serologic !attern of Acute )C8 Infection -it%!rogression to C%ronic Infection


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Symptoms H7$

Time after E>posure

T i t e r

anti$)C8

A=T

Normal

2 3 & * . 0 1 3 & * .earsMont%s

)C8 RNA


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)C8 !revalence by Selecte" 9roups

Unite" States


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2 32 &2 *2 .2 02 12 '2


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8) SerologyReliable serological tests %ave only recently

become available(

)C8$specific Ig9 in"icates e>posure# not

infectivity

) '*! "etects viral genome in patientJs serum


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Treatment# !revention# an" Control


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# #

Recombinant interferon$alp%a is t%e only/no-n effective treatment for )C8(

Illicit "rug abuse an" transfusion are t%e most

i"entifiable sources of )C8 viruses(


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Hepatitis & virus


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Hepatitis D Delta! Virus

HBsA% anti%en


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HBsA%

5A

%

!eplication


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Transcription an" replication of t%e )D8genome are unusual( Specifically# t%e %ost cellKs

RNA polymerase II ma/es an RNA copy#

replicates t%e genome# an" ma/es mRNA(

Geographic Distribution of HDV Infectio


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HD# $revalence

Hi%&

'nterme(iate

)o*

#ery )o*

5o Data

Tai*an

$acific 'sla

!at%ogenesis


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Sprea" in bloo"# semen# an" vaginal secretion( It can replicate an" cause "isease only in

people -it% active )B8 infections(

Replication of t%e "elta agent results incytoto>icity an" liver "amage(


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Hepatitis D - "linical

Features


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. Coinfection

;severe acute disease

; low risk of c7ronic infection

. Superinfection

;usually develop c7ronic H


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&ime after*+ osure

& i t e r anti-

HBs

'ymptoms

A,&*leated

&otal anti-

HDV

IgM anti-HDV

HDV ./A

HBsAg

HBV - HDV 'uperinfection&ypical 'erologic "ourse

0aundice


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&ime after

& i t e

r

'ymptoms

A,&&otal anti-HDV

IgM anti-HDV

HDV ./A

HBsAg

=aboratory Diagnosis


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Detect t%e "elta antigen of antibo"ies E=ISA an" RIA

Hepatitis D - 1reention


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. HBV-H


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Hepatitis E Virus

Structure an" 9enome


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*2$*&nm non$envelope" particle s7s +H,sense RNA genome # L'(0b(

9enetic organi;ation similar +not i"entical, to

Caliciviruses


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Hepatitis * - "linical

Features


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. /ncubation period0 Average &$ days1ange %!-'$ days

. Case-fatality rate0 Overall5 %6-"6

8regnant wo9en5 %!6-(!6. /llness severity0 /ncreased wit7 age

. C7ronic sequelae0 >one identi?ed

Geographic Distribution ofHepatitis *


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8revention and Control @easures

for ravelers to H:V-:nde9ic1egions


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. Aoid drin)ing 2ater and beerages 2ithice! of un)no2n purity3 uncoo)ed shellsh3and uncoo)ed fruit4egetables not peeled orprepared by traeler

. IG prepared from donors in (esterncountries does not preent infection

. 5n)no2n e6cacy of IG prepared from donorsin endemic areas

. Vaccine7

1egions

Epi"emiology


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T%e "elta agent infects c%il"ren an" a"ults-it% un"erlying )B8 infection# an" people

-%o are persistently infecte" -it% bot% )B8

an" )D8 are a source for t%e virus(

hepatitisvirus

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