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Hepatitis A-E Viruses. An Overview. Viral Hepatitis - Historical Perspectives. Enterically transmitted. “ Infectious”. A. E. Viral hepatitis. NANB. Parenterally transmitted. B. D. C. “ Serum”. F, G, TTV ? other. Type of Hepatitis. A. B. C. D. E. Source of. feces. blood/.

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slide2

Viral Hepatitis - Historical Perspectives

Enterically

transmitted

“Infectious”

A

E

Viral hepatitis

NANB

Parenterally

transmitted

B

D

C

“Serum”

F, G, TTV

? other

slide3

Type of Hepatitis

A

B

C

D

E

Source of

feces

blood/

blood/

blood/

feces

virus

blood-derived

blood-derived

blood-derived

body fluids

body fluids

body fluids

Route of

fecal-oral

percutaneous

percutaneous

percutaneous

fecal-oral

transmission

permucosal

permucosal

permucosal

Chronic

no

yes

yes

yes

no

infection

Prevention

pre/post-

pre/post-

blood donor

pre/post-

ensure safe

exposure

exposure

screening;

exposure

drinking

immunization

immunization

risk behavior

immunization;

water

modification

risk behavior

modification

slide5

Hepatitis A - Clinical Features

  • Incubation period: Average 30 days

Range 15-50 days

  • Jaundice by <6 yrs, <10%age group: 6-14 yrs, 40%-50% >14 yrs, 70%-80%
  • Complications: Fulminant hepatitis Cholestatic hepatitis Relapsing hepatitis
  • Chronic sequelae: None
slide6

Hepatitis A Infection

Typical Serological Course

Total anti-HAV

Symptoms

Titre

ALT

Fecal

HAV

IgM anti-HAV

4

5

6

12

24

0

1

2

3

Months after exposure

slide7

Hepatitis A Virus Transmission

  • Close personal contact(e.g., household contact, sex contact, child day care centers)
  • Contaminated food, water(e.g., infected food handlers, raw shellfish)
  • Blood exposure (rare)(e.g., injecting drug use, transfusion)
slide8

Global Patterns of Hepatitis A Virus Transmission

Disease

Peak Age

Endemicity

Rate

of Infection

Transmission Patterns

High

Low to

Early

Person to person;

High

childhood

outbreaks uncommon

Moderate

High

Late

Person to person;

childhood/

food and waterborne

young adults

outbreaks

Low

Low

Young adults

Person to person;

food and waterborne

outbreaks

Very low

Very low

Adults

Travelers; outbreaks

uncommon

laboratory diagnosis
Laboratory Diagnosis
  • Acute infection is diagnosed by the detection of HAV-IgM in serum by EIA.
  • Past Infection i.e. immunity is determined by the detection of HAV-IgG by EIA.
slide11

Hepatitis A Vaccination Strategies

Epidemiologic Considerations

  • Many cases occur in community-wide outbreaks
    • no risk factor identified for most cases
    • highest attack rates in 5-14 year olds
    • children serve as reservoir of infection
  • Persons at increased risk of infection
    • travelers
    • homosexual men
    • injecting drug users
slide12

Hepatitis A Prevention - Immune Globulin

  • Pre-exposure
    • travelers to intermediate and high HAV-endemic regions
  • Post-exposure (within 14 days)

Routine

    • household and other intimate contacts

Selected situations

    • institutions (e.g., day care centers)
    • common source exposure (e.g., food prepared by infected food handler)
slide14

Hepatitis B - Clinical Features

  • Incubation period: Average 60-90 days

Range 45-180 days

  • Clinical illness (jaundice): <5 yrs, <10%5 yrs, 30%-50%
  • Acute case-fatality rate: 0.5%-1%
  • Chronic infection: <5 yrs, 30%-90% 5 yrs, 2%-10%
  • Premature mortality fromchronic liver disease: 15%-25%
spectrum of chronic hepatitis b diseases
Spectrum of Chronic Hepatitis B Diseases

1. Chronic Persistent Hepatitis - asymptomatic

2. Chronic Active Hepatitis - symptomatic exacerbations of hepatitis

3. Cirrhosis of Liver

4. Hepatocellular Carcinoma

slide16

Acute Hepatitis B Virus Infection with Recovery

Typical Serologic Course

Symptoms

anti-HBe

HBeAg

Total anti-HBc

Titre

anti-HBs

IgM anti-HBc

HBsAg

0

4

8

12

16

24

28

32

52

100

20

36

Weeks after Exposure

slide17

Progression to Chronic Hepatitis B Virus Infection

Typical Serologic Course

Acute

(6 months)

Chronic

(Years)

HBeAg

anti-HBe

HBsAg

Total anti-HBc

Titre

IgM anti-HBc

Years

0

4

8

16

20

24

28

36

12

32

52

Weeks after Exposure

slide18

Outcome of Hepatitis B Virus Infection

by Age at Infection

100

100

80

80

Chronic Infection (%)

60

60

Chronic Infection

Symptomatic Infection (%)

40

40

Chronic Infection (%)

20

20

Symptomatic Infection

0

0

1-6 months

7-12 months

Older Children

and Adults

Birth

1-4 years

Age at Infection

slide19

Global Patterns of Chronic HBV Infection

  • High (>8%): 45% of global population
    • lifetime risk of infection >60%
    • early childhood infections common
  • Intermediate (2%-7%): 43% of global population
    • lifetime risk of infection 20%-60%
    • infections occur in all age groups
  • Low (<2%): 12% of global population
    • lifetime risk of infection <20%
    • most infections occur in adult risk groups
slide21

Concentration of Hepatitis B Virus in Various Body Fluids

Low/Not

High

Moderate

Detectable

blood

semen

urine

serum

vaginal fluid

feces

wound exudates

saliva

sweat

tears

breastmilk

slide22

Hepatitis B Virus

Modes of Transmission

  • Sexual - sex workers and homosexuals are particular at risk.
  • Parenteral - IVDA, Health Workers are at increased risk.
  • Perinatal - Mothers who are HBeAg positive are much more likely to transmit to their offspring than those who are not. Perinatal transmission is the main means of transmission in high prevalence populations.
diagnosis
Diagnosis
  • A battery of serological tests are used for the diagnosis of acute and chronic hepatitis B infection.
  • HBsAg - used as a general marker of infection.
  • HBsAb - used to document recovery and/or immunity to HBV infection.
  • anti-HBc IgM - marker of acute infection.
  • anti-HBcIgG - past or chronic infection.
  • HBeAg - indicates active replication of virus and therefore infectiveness.
  • Anti-Hbe - virus no longer replicating. However, the patient can still be positive for HBsAg which is made by integrated HBV.
  • HBV-DNA - indicates active replication of virus, more accurate than HBeAg especially in cases of escape mutants. Used mainly for monitoring response to therapy.
treatment
Treatment
  • Interferon - for HBeAg +ve carriers with chronic active hepatitis. Response rate is 30 to 40%.
  • Lamivudine - a nucleoside analogue reverse transcriptase inhibitor. Well tolerated, most patients will respond favorably. However, tendency to relapse on cessation of treatment. Another problem is the rapid emergence of drug resistance.
  • Successful response to treatment will result in the disappearance of HBsAg, HBV-DNA, and seroconversion to HBeAg.
prevention
Prevention
  • Vaccination - highly effective recombinant vaccines are now available. Vaccine can be given to those who are at increased risk of HBV infection such as health care workers. It is also given routinely to neonates as universal vaccination in many countries.
  • Hepatitis B Immunoglobulin - HBIG may be used to protect persons who are exposed to hepatitis B. It is particular efficacious within 48 hours of the incident. It may also be given to neonates who are at increased risk of contracting hepatitis B i.e. whose mothers are HBsAg and HBeAg positive.
  • Other measures - screening of blood donors, blood and body fluid precautions.
slide26

Hepatitis C Virus

capsid

envelope

protein

protease/helicase

RNA-dependent

RNA polymerase

c22

c-100

33c

5’

3’

NS3

NS5

core

E1

E2

NS2

NS4

hypervariable

region

slide27

Hepatitis C - Clinical Features

Incubation period: Average 6-7 wks

Range 2-26 wks

Clinical illness (jaundice): 30-40% (20-30%)

Chronic hepatitis: 70%

Persistent infection: 85-100%

Immunity: No protective antibody

response identified

chronic hepatitis c infection
Chronic Hepatitis C Infection
  • The spectrum of chronic hepatitis C infection is essentially the same as chronic hepatitis B infection.
  • All the manifestations of chronic hepatitis B infection may be seen, albeit with a lower frequency i.e. chronic persistent hepatitis, chronic active hepatitis, cirrhosis, and hepatocellular carcinoma.
slide29

Hepatitis C Virus Infection

Typical Serologic Course

anti-HCV

Symptoms

Titre

ALT

Normal

6

1

2

3

4

0

1

2

3

4

5

Months

Years

Time after Exposure

slide30

Risk Factors Associated with Transmission of HCV

  • 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 diagnosis1
Laboratory Diagnosis
  • HCV antibody - generally used to diagnose hepatitis C infection. Not useful in the acute phase as it takes at least 4 weeks after infection before antibody appears.
  • HCV-RNA- various techniques are available e.g. PCR and branched DNA. May be used to diagnose HCV infection in the acute phase. However, its main use is in monitoring the response to antiviral therapy.
  • HCV-antigen - an EIA for HCV antigen is available. It is used in the same capacity as HCV-RNA tests but is much easier to carry out.
treatment1
Treatment
  • Interferon - may be considered for patients with chronic active hepatitis. The response rate is around 50% but 50% of responders will relapse upon withdrawal of treatment.
  • Ribavirin- there is less experience with ribavirin than interferon. However, recent studies suggest that a combination of interferon and ribavirin is more effective than interferon alone.
slide34

Prevention of Hepatitis C

  • Screening of blood, organ, tissue donors
  • High-risk behavior modification
  • Blood and body fluid precautions
slide35

Hepatitis D (Delta) Virus

antigen

HBsAg

RNA

slide36

Hepatitis D - Clinical Features

  • Coinfection
    • severe acute disease.
    • low risk of chronic infection.
  • Superinfection
    • usually develop chronic HDV infection.
    • high risk of severe chronic liver disease.
    • may present as an acute hepatitis.
slide37

Hepatitis D Virus Modes of Transmission

  • Percutanous exposures
    • injecting drug use
  • Permucosal exposures
    • sex contact
slide38

HBV - HDV Coinfection

Typical Serologic Course

Symptoms

ALT Elevated

Titre

anti-HBs

IgM anti-HDV

HDV RNA

HBsAg

Total anti-HDV

Time after Exposure

slide39

HBV - HDV Coinfection

Typical Serologic Course

Symptoms

ALT Elevated

Titre

anti-HBs

IgM anti-HDV

HDV RNA

HBsAg

Total anti-HDV

Time after Exposure

slide40

HBV - HDV Superinfection

Typical Serologic Course

Jaundice

Symptoms

Total anti-HDV

ALT

Titre

HDV RNA

HBsAg

IgM anti-HDV

Time after Exposure

slide42

Hepatitis D - Prevention

  • HBV-HDV Coinfection

Pre or postexposure prophylaxis to prevent HBV infection.

  • HBV-HDV Superinfection

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

slide44

Hepatitis E - Clinical Features

  • Incubation period: Average 40 days
  • Range 15-60 days
  • Case-fatality rate: Overall, 1%-3%Pregnant women, 15%-25%
  • Illness severity: Increased with age
  • Chronic sequelae: None identified
slide45

Hepatitis E Virus Infection

Typical Serologic Course

Symptoms

IgG anti-HEV

ALT

Titer

IgM anti-HEV

Virus in stool

0

1

2

3

4

5

6

7

8

9

10

11

12

13

Weeks after Exposure

slide46

Hepatitis E -

Epidemiologic Features

  • Most outbreaks associated with faecally contaminated drinking water.
  • Several other large epidemics have occurred since in the Indian subcontinent and the USSR, China, Africa and Mexico.
  • In the United States and other nonendemic areas, where outbreaks of hepatitis E have not been documented to occur, a low prevalence of anti-HEV (<2%) has been found in healthy populations. The source of infection for these persons is unknown.
  • Minimal person-to-person transmission.
slide48

Prevention and Control Measures for Travelers to HEV-Endemic Regions

  • Avoid drinking water (and beverages with ice) of unknown purity, uncooked shellfish, and uncooked fruit/vegetables not peeled or prepared by traveler.
  • IG prepared from donors in Western countries does not prevent infection.
  • Unknown efficacy of IG prepared from donors in endemic areas.
  • Vaccine?
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