Hepatitis A-E Viruses

Viral Hepatitis Hepatitis - Historical Historical Perspective Perspectivess

Hepatitis A-E Viruses

“Infectious”

A

Viral hepatitis

An Overview

Enterically transmitted

E

NANB Parenterall

B D

“Serum”

C y F, G, TTV ? other

Characteristics of Hepatitis Viruses virus

Hep at at itit is is A

Hep at at itit is is B

Hep at at itit is is C

transmitted

Characteristics of Hepatitis Viruses

Hep at at ititi s D

Hep at at itit is is E

VIRUS

HA V

HB V

HCV

HDV

HEV

Family

Picorna ornavir virida idae

Hepadn padnavirid aviridae

Flavivirid iviridae ae

Unclassifie ssified d

Unclas nclassified sified

Transmission

Feca Fecall oral paren parenteral teral

pare parente nteral

paren parenteral teral

Feca Fecal-o l-ora rall

Genus enus

Hepatovirus virus

Orthohep ohepadna adnavirus virus

Hepaciviru civirus s

Deltavir tavirus us

Hepat epatitis itis Elike

Prevalence

high

high

moderate

Low, regional

regional

Virio irion n

27nm, icosahedral

42nm 42nm, spherical erical

60nm 60nm, spherical

35nm, spherical

30-32 icosahedral

Fulminant dse

rare

rare

rare

frequent

In pregnancy

Chronic dse

never

often

often

often

never  

Envelope

no

Yes (HBsAg)

yes

Yes (HBsAg)

no

Oncogenic

no

yes

yes

?

no

Genome

ssRNA

dsDNA

ssRNA

ssRNA

ssRNA

Genome size

7.5kb

3.2 kb

9.4 kb

1.7kb

7.6 kb

Stability

Heat & acid acid stable

Acid sens sensitive itive

Ethe Ether and acid Acid sensitive sensitive sensitive

Heat Heat stable

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

feces

fecal ecal-o -ora rall no

B blood/   blood-derived body fluids

C

D

HEPATITIS A VIRUS (HAV) E

blood/  blood/  feces blood-derived blood-derived body fluids body fluids

perc percut utan aneo eous us percutaneous 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

• This picornavirus is the causative agent of  infectious hepatitis.  –  single strand, 3’‐

polyadenylated, positive sense RNA genome  –  surrounded by a naked (unenveloped) icosahedral capsid that is around 28 nm in diameter  –  at the 5’ end of the of  the RNA strand is a viral protein called VPg. of  HAV.  –  only one serotype of HAV.

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Hepatitis A ‐ Clinical Features





Incubation period:

Clinical Manifestations

Average 30 days Range 15‐50 days 2 wks

No

All ages

Yes

>/=1yo

IG:0.02ml/kg + Hepatitis A vaccine

• DS DNA Virus • Hepadnavirus • May exist in multiple forms:  –  Spherical particles (22nm) of  filamentous forms  –  Tubular of filamentous  –  Larger, 42nm spherical virions (originally referred to as Dane particle)

No prophylaxis

• Envelope contains HBsAg and surrounds the

Hepatitis A vaccine

nucleocapsid core containing HBcAg. • Humans: only reservoir

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Clinical manifestations

Hepatitis Hepatitis B - Clinical Clinical Features Features

Anicteric‐majority of cases of  cases including children 

Incubation period:

Average 60‐90 days Range 45‐180 days



Clinical illness (jaundice):

19 y/o Casual Immunosuppressed Immunosuppressed or hemodialysispatients

Vaccine schedule

HBIG Dose (u/L)

HBIG Schedule

Birth, 1, 6mo Birth, 1-2,6-18 mo

0.5 None

Within 12 hr of birth

0,1, and 6 mo

None

Hepatitis C Virus capsid capsid envelo envelope pe protein c22

Exposure, 1 and 6 mo Exposure, 1 and 6 mo None none

0.06/kg 0.06/kg None None

Exposure, 1 and 6 mo Exposure, 1 and 6 mo

None None None

Exposure, 1 qnd 6 mo

none

At exposure At exposure

RNA-dependentRNA RNA polymerase

protease/helicase 33c

c-100

5’

3’ core E1

E2

hypervariable region

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NS 2

NS 3

NS 4

NS 5

Hepatitis C ‐ Clinical Features

Hepatitis C Degree of exposure

Seroprevalence

Large,repeated exposure( exposure(IV IV drug users,hemophiliacs before 1987

60=90%

Frequent ,smaller exposure(hemodialy sis pt)

10-20%

Inapparent percutaneous exposure(sex worker)

1-10%

Spor Sporad adic ic expo exposu sure re

1%

• Transmission : blood or body fluid • Parenteral exposure to HCV‐ infected blood: primary route; seroprevalence depend on degree of exposure of  exposure

Incubation period:

Average 6‐7 wks Range 2‐26 wks

Clinical manifestations: Asymptomatic illness‐ majority of cases of  cases Symptomatic illness: mimics hepatitis A or B •

Perinatal transmission is uncommon(5‐6%)

Extrahepatic manifestations: essential mixed cryoglobulinemia,cutaneous vasculitis,peripheral neuropathy, glomerulonephritis,etc.

Risk Factors Associated with Transmission of HCV of  HCV

Chronic Hepatitis C Infection • HCV most likely to cause chronic infection;~85% become chronic

• After ~20‐30 years, about 25% ultimately

progress to

cirrhosis, liver failure & occasionally primary hepatoCa

• Hepatocellu Hepatocellular lar Ca associated with HCV, which is less effective than HBV in causing primary hepatoCa almost always occurs with cirrhosis; results from chronic inflammation & necrosis rather than oncogenic effect of virus of  virus



Transfusion or transplant from infected donor



Injecting drug use



Hemodialysis (yrs on treatment)



Accidental injuries with needles/sharps



Sexual/household exposure to anti‐HCV‐positive contact



Multiple sex partners



Birth to HCV‐infected mother

Laboratory Diagnosis

 Treatment

• HCV antibody ‐ Not useful in the acute phase ; at least 4 weeks after infection before (+)

• HCV‐RNA ‐ PCR and branched DNA; useful in

phase; used mainly in monitoring the acute phase; response to antiviral therapy.

• HCV‐antigen ‐ by EIA , much easier procedure

• Interferon ‐

considered for chronic active hepatitis; hepatitis;respo response nse rate ~ 50% but 50% of  responders will relapse upon withdrawal of Tx. of  Tx.

• Ribavirin ‐ recent studies suggest that a combination of  interferon and ribavi ribavirin rin is more effective than interferon alone.

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Hepatitis D (Delta) Virus

Prevention of Hepatitis C

antigen



Screening of blood, of  blood, organ, tissue donors



High‐risk behavior modification



Blood and body fluid precautions

HBsAg

RNA

Hepatitis D Virus Modes of Transmission

Hepatitis D • Is a highly defective virus of  a co‐infecting  –  it cannot produce infective virions without the help of a helper virus  HBV ‐‐ supplies the HBsAg surface protein.



of  the cell, HDV acquires a membrane • In budding out of the

Percutanous exposures  injecting

containing HBsAg.  –  HDV can only form an infectious particle if the if  the cell in which it replicates is co‐infected with HBV since the latter provides the surface



drug use

Permucosal exposures

HBsAg which is required for reinfection of another of  another cell.

 sex

• HDV has a small circular RNA genome (1,700 bases) that

contact

encodes a protein called the delta antigen. antigen. This complexes with the RNA.

• The RNA is single stranded negative sense and is a covalently closed circle.

Hepatitis Hepa titis D - Clinical Clinical Feature Features s

Hepatitis D ‐ Prevention



Coinfection  – severe acute disease.  – low risk of chronic of  chronic infection.  Superinfection



HBV‐HDV Coinfection Pre or postexposure prophylaxis to prevent HBV infection.

acute illness is rare  – chronic infection is common risk of fulminant of fulminant hepatitis is highest; suspect in any child w/ acute liver failure



HBV‐HDV Superinfection Education to reduce risk behaviors among persons with chronic HBV infection.

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Hepatitis E Virus

Hepatitis E ‐ Clinical Features

• enteric non‐A, non‐B hepatitis 

Incubation period:

Average 40 days Range 15‐60 days



Case‐fatality rate:

Overall, 1%‐3% Pregnant women, women, 15%‐25%



Illness severity:

Increased with age



Chronic sequelae:

None identified

Hepatitis E Virus Infection

Hepatitis F (HFV)

Typical Serologic Course Symptoms

IgG anti-HEV anti-HEV

ALT

Titer

• ‐in 1994, french researchers isolated an enteric agent responsible for sporadic non‐ A‐E hepatitis ‐not confirmed by others

IgM anti-HEV anti-HEV

Virus in stool

0

1

2

3

4

5

6

7

8

9

10

11

12

13

Weeks after Exposure

Hepatitis G (HGV) ‐RNA virus, flaviviridae family, 27% homology to HCV ‐reported in adults and children of  adults with chronic hepatitis B ‐seen in HIV pts and in 10‐20% of adults and hepatits C

THE END

‐primary source: transfusion; organ transplant, IV drug use, hemodialysis, sexual transmission

•

of  cases of non of  non‐A‐E ‐ accounts for only small proportion of cases hepatitis

‐most most infection not associated with hepatic inflammation ;doesn’t seem to worsen coinfection with hepatitis B or C

‐diagnosis: HGV RNA PCR ‐prevention: none Edited by KDE

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