Hepatitis A-E Viruses

An Overview

Viral Hepatitis - Historical Perspectives

Infectious

A
NANB

Enterically E transmitted

Viral hepatitis

Serum

B D

Parenterally C transmitted F, G, TTV ? other

Type of Hepatitis
A
Source of virus Route of transmission Chronic infection Prevention feces

E
feces

blood/ blood/ blood/ blood-derived blood-derived blood-derived body fluids body fluids body fluids percutaneous percutaneous percutaneous permucosal permucosal permucosal yes yes yes

fecal-oral

fecal-oral

no

no

pre/postexposure immunization

pre/postexposure immunization

blood donor pre/postscreening; exposure risk behavior immunization; modification risk behavior modification

ensure safe drinking ater

Hepatitis A Virus

Hepatitis A - (linical *eatures

Incubation period: Jaundice by age group: (o)plications: (+ronic se,uelae:

Average 30 days Range 15-50 days ! yrs" 10# !-1$ yrs" $0#-50# %1$ yrs" &0#-'0# *ul)inant +epatitis (+olestatic +epatitis Relapsing +epatitis -one

Hepatitis A In.ection
/ypical 3erological (ourse
Symptoms

/otal antiHAV

/itre

A0/

Fecal HAV

Ig1 anti-HAV

12

24

1ont+s a.ter e2posure

Hepatitis A Virus /rans)ission

(lose personal contact 4e5g5" +ouse+old contact" se2 contact" c+ild day care centers6 (onta)inated .ood" 7ater 4e5g5" in.ected .ood +andlers" ra7 s+ell.is+6 8lood e2posure 4rare6 4e5g5" in9ecting drug use" trans.usion6

Global Patterns of Hepatitis A Virus Transmission

Disease Peak Age Endemicity Rate of Infection Hig+ 1oderate 0o7 to Hig+ Hig+ :arly c+ild+ood 0ate c+ild+ood= young adults Transmission Patterns Person to person; outbrea<s unco))on Person to person; .ood and 7aterborne outbrea<s

0o7

Very lo7

>oung adults Person to person; .ood and 7aterborne outbrea<s Very lo7 Adults /ravelers; outbrea<s unco))on

0o7

Laboratory Diagnosis

Acute in.ection is diagnosed by t+e detection o. HAV-Ig1 in seru) by :IA5 Past In.ection i5e5 i))unity is deter)ined by t+e detection o. HAV-Ig? by :IA5

Hepatitis A Vaccination Strategies Epidemiologic Considerations

1any cases occur in co))unity-7ide outbrea<s no ris< .actor identi.ied .or )ost cases +ig+est attac< rates in 5-1$ year olds c+ildren serve as reservoir o. in.ection Persons at increased ris< o. in.ection travelers +o)ose2ual )en in9ecting drug users

Hepatitis A Prevention - Immune Globulin

Pre-e2posure

travelers to inter)ediate HAV-ende)ic regions

and

+ig+

Post-e2posure 47it+in 1$ days6

Routine +ouse+old and ot+er inti)ate contacts 3elected situations institutions 4e5g5" day care centers6 co))on source e2posure 4e5g5" .ood prepared by in.ected .ood +andler6

Hepatitis B Virus

Hepatitis B - Clinical Features

Incubation period: (linical illness 49aundice6: Acute case-.atality rate: (+ronic in.ection: Pre)ature )ortality .ro) c+ronic liver disease: Average !0-@0 days Range $5-1'0 days 5 yrs" 10# 5 yrs" 30#-50# 055#-1# 5 yrs" 30#-@0# 5 yrs" A#-10# 15#-A5#

3pectru) o. (+ronic Hepatitis 8 Biseases

15 (+ronic asy)pto)atic Persistent Hepatitis -

A5 (+ronic Active Hepatitis sy)pto)atic e2acerbations o. +epatitis 35 (irr+osis o. 0iver $5 Hepatocellular (arcino)a

Acute Hepatitis B Virus Infection with Recovery Typical Serologic Course

Symptoms H eAg anti!H e

/itre
H sAg

Total anti! H c anti!H s

Ig" anti!H c

12 16 20 24 28 32 36

52

100

Weeks after Exposure

Progression to Chronic Hepatitis B Virus Infection

Typical Serologic Course
!cute "# months$ H eAg H8sAg /otal anti-H8c Chronic "%ears$ anti!H e

Titre

Ig1 anti-H8c

0 4 8 12 16 20 24 28 32 36

52

Years

Weeks after Exposure

Outcome of Hepatitis B Virus Infection by Age at Infection 100

80
Ch ron ic Inf ect ion (%)

100 80
!"#to"atic Infection (%)

60

#$ronic Infection
Chronic Infection (%)

60

40

40

20 Symptomatic Infection 0 Birth 1$6 "onths %$12 "onths 1$4 !ears

20

0 &'(er Chi'(ren an( A()'ts

Age at Infection

Global Patterns of Chronic HBV Infection

Hig+ 4%'#6: $5# o. global population

li.eti)e ris< o. in.ection %!0# early c+ild+ood in.ections co))on

Inter)ediate 4A#-&#6: $3# o. global population

li.eti)e ris< o. in.ection A0#-!0# in.ections occur in all age groups

0o7 4 A#6: 1A# o. global population

li.eti)e ris< o. in.ection A0# )ost in.ections occur in adult ris< groups

#oncentration of Hepatitis Virus in Various ody )luids

Hig$ blood seru) 7ound e2udates "oderate se)en vaginal .luid saliva %o&'(ot Detectable urine .eces s7eat tears breast)il<

Hepatitis Virus "odes of Transmission

3e2ual - se2 7or<ers and +o)ose2uals are particular at ris<5 Parenteral - IVBA" Healt+ Cor<ers are at increased ris<5 Perinatal - 1ot+ers 7+o are H8eAg positive are )uc+ )ore li<ely to trans)it to t+eir o..spring t+an t+ose 7+o are not5 Perinatal trans)ission is t+e )ain )eans o. trans)ission in +ig+ prevalence populations5

Diagnosis
A battery o. serological tests are used .or t+e diagnosis o. acute and c+ronic +epatitis 8 in.ection5 H8sAg - used as a general )ar<er o. in.ection5 H8sAb - used to docu)ent recovery and=or i))unity to H8V in.ection5 anti-H8c Ig1 - )ar<er o. acute in.ection5 anti-H8cIg? - past or c+ronic in.ection5 H8eAg - indicates active replication o. virus and t+ere.ore in.ectiveness5 Anti-Hbe - virus no longer replicating5 Ho7ever" t+e patient can still be positive .or H8sAg 7+ic+ is )ade by integrated H8V5 H8V-B-A - indicates active replication o. virus" )ore accurate t+an H8eAg especially in cases o. escape )utants5 Dsed )ainly .or )onitoring response to t+erapy5

Prevention

Vaccination - +ig+ly e..ective reco)binant vaccines are no7 available5 Vaccine can be given to t+ose 7+o are at increased ris< o. H8V in.ection suc+ as +ealt+ care 7or<ers5 It is also given routinely to neonates as universal vaccination in )any countries5 Hepatitis 8 I))unoglobulin - H8I? )ay be used to protect persons 7+o are e2posed to +epatitis 85 It is particular e..icacious 7it+in $' +ours o. t+e incident5 It )ay also be given to neonates 7+o are at increased ris< o. contracting +epatitis 8 i5e5 7+ose )ot+ers are H8sAg and H8eAg positive5 Et+er )easures - screening o. blood donors" blood and body .luid precautions5

Hepatitis C - Clinical Features

Incubation period: 7<s (linical illness 49aundice6: (+ronic +epatitis: Persistent in.ection: I))unity: identi.ied Average !-& 7<s Range A-A! 30-$0# 4A0-30#6 &0# '5-100# -o protective antibody response

Chronic Hepatitis C Infection

/+e spectru) o. c+ronic +epatitis ( in.ection is essentially t+e sa)e as c+ronic +epatitis 8 in.ection5 All t+e )ani.estations o. c+ronic +epatitis 8 in.ection )ay be seen" albeit 7it+ a lo7er .re,uency i5e5 c+ronic persistent +epatitis" c+ronic active +epatitis" cirr+osis" and +epatocellular carcino)a5

Hepatitis C Virus Infection

Typical Serologic Course
anti-HCV
Symptoms

Titre

ALT

Normal 0 1 2 3 4 Months 5 6 1 2 3 Years 4

Time after Exposure

Risk Factors Associated with Transmission of HCV

/rans.usion or transplant .ro) in.ected donor In9ecting drug use He)odialysis 4yrs on treat)ent6 Accidental in9uries 7it+ needles=s+arps 3e2ual=+ouse+old e2posure to anti-H(V-positive contact 1ultiple se2 partners 8irt+ to H(V-in.ected )ot+er

Laboratory Diagnosis

H(V antibody - generally used to diagnose +epatitis ( in.ection5 -ot use.ul in t+e acute p+ase as it ta<es at least $ 7ee<s a.ter in.ection be.ore antibody appears5 H(V-R-A - various tec+ni,ues are available e5g5 P(R and branc+ed B-A5 1ay be used to diagnose H(V in.ection in t+e acute p+ase5 Ho7ever" its )ain use is in )onitoring t+e response to antiviral t+erapy5 H(V-antigen - an :IA .or H(V antigen is available5 It is used in t+e sa)e capacity as H(V-R-A tests but is )uc+ easier to carry out5

Prevention of Hepatitis C
3creening o. blood" organ" tissue donors Hig+-ris< be+avior )odi.ication 8lood and body .luid precautions

Hepatitis D (Delta) Virus

antigen *BsAg

+,A

Hepatitis D - Clinical Features

(oin.ection F severe acute disease5 F lo7 ris< o. c+ronic in.ection5 3uperin.ection F usually develop c+ronic HBV in.ection5 F +ig+ ris< o. severe c+ronic liver disease5 F )ay present as an acute +epatitis5

Hepatitis D Virus Modes of Transmission

Percutanous e2posures in9ecting drug use Per)ucosal e2posures se2 contact

HBV - HDV Coinfection

Typical Serologic Course
Symptoms ALT Elevated

Titre
IgM anti-HDV

anti-H8s

HDV RNA HBsAg /otal anti-HBV

Time after Exposure

HBV - HDV Superinfection

Typical Serologic Course
Jaundice Symptoms ALT Total anti-HDV

Titre

HDV RNA HBsAg IgM anti-HDV

Time after Exposure

Hepatitis D - Prevention

H8V-HBV (oin.ection Pre or poste2posure prop+yla2is to prevent H8V in.ection5

H8V-HBV 3uperin.ection :ducation to reduce ris< be+aviors a)ong persons 7it+ c+ronic H8V in.ection5

Hepatitis E Virus

Hepatitis : - (linical *eatures

Incubation period: (ase-.atality rate:

Average $0 days Range 15-!0 days Everall" 1#-3# Pregnant 7o)en" 15#-A5# Increased 7it+ age -one identi.ied

Illness severity: (+ronic se,uelae:

Hepatitis E Virus Infection

Typical Serologic Course
Symptoms

ALT

IgG anti-HEV

Titer
Virus in stool

IgM anti-HEV

10

11

12

13

Weeks after Exposure

Hepatitis E Epidemiologic Features

1ost outbrea<s associated 7it+ .aecally conta)inated drin<ing 7ater5 3everal ot+er large epide)ics +ave occurred since in t+e Indian subcontinent and t+e D33R" (+ina" A.rica and 1e2ico5 In t+e Dnited 3tates and ot+er nonende)ic areas" 7+ere outbrea<s o. +epatitis : +ave not been docu)ented to occur" a lo7 prevalence o. anti-H:V 4 A#6 +as been .ound in +ealt+y populations5 /+e source o. in.ection .or t+ese persons is un<no7n5 1ini)al person-to-person trans)ission5

Prevention and Control Measures for Travelers to HEV-Endemic Regions

Avoid drin<ing 7ater 4and beverages 7it+ ice6 o. un<no7n purity" uncoo<ed s+ell.is+" and uncoo<ed .ruit=vegetables not peeled or prepared by traveler5 I? prepared .ro) donors in Cestern countries does not prevent in.ection5 Dn<no7n e..icacy o. I? prepared .ro) donors in ende)ic areas5 VaccineG