Viral Hepatitis

Hugh B. Fackrell

Filename: Hepatite.ppt

8/27/2019
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 Hepatitis Virus Outline

Definitions
Classification
Structure
Multiplication
Clinical manifestations
Epidemiology
Diagnosis
Control 8/27/2019
2 Baron’s Web Site
 Hepatitis

an ancient disease, the etiology has only

recently (50 yrs.) been revealed.

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 Hepatitis

An inflammatory disease

necrosis
of hepatocytes
mononuclear response destroys liver architecture

Liver excretion of bile pigments such as bilirubin

into the intestine is interrupted

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 Bilirubin

Bilirubin: greenish-yellow pigment

accumulates in the blood and tissues
Jaundice -
 yellow tinge in the skin and eyes
caused by bilirubin

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 Types of Jaundice

Pre hepatic: Hemolytic Jaundice

normal feces, anemia, reticulocytes
Hepatic: Hepatocellular Jaundice
 fecal fat, bilirubinuria, Alkaline phosphatase
high, gamma globulins high
Post Hepatic: Obstructive Jaundice
fecal fat, bilirubinuria, alkaline phosphatase
high
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 Jaundice of the Newborn

Premature infants
bilirubin increases from birth
peaks at one week
caused by
1:excessivehemolysis
2:immature liver function

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 Hepatitis symptoms

Swelling and
tenderness of liver
Jaundice -yellow
tinge in the skin and
eyes
dark urine
transaminase, alkaline
phosphatase levels
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 Viral Hepatitis

Liver infection caused by several

UNRELATED VIRUSES
Inflammation and necrosis of the liver
50% of HAV & HBV are subclincal

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 Hepatitis types

Hepatitis A - HAV "infectious hepatitis"

Hepatitis B - HBV "serum hepatitis"
Hepatitis C - HCV non A, non B
Hepatitis D - HDV Delta virus
Hepatitis E - HEV similar to type “A”

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 Hepatitis A

“Infectious hepatitis”
“Epidemic hepatitis”
HAV

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 Hepatitis A
Clinical manifestations
asymptotic or anicteric in children
3-5 week incubation period
liver inflammation
malaise - flu like symptoms
self limiting
low mortality

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 Hepatitis A
Structure
Picornavirus
Only one serotype
Enterovirus type 72
27-29 nm icosahedral
 ssRNA

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 Hepatitis A
Host Defenses
 antibodies develop late in incubation period
IgM
within a week of dark urine
peaks a week later
lasts 40-60 days

IgG
after IgM
peaks 60-80 days
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 Hepatitis A
Epidemiology
Global distribution- underreported
Fecal-oral route,
person to person
 water
Overcrowding & poor sanitation
 Infected food handlers common vector

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 Annual Incidence Viral food
borne diseases
Norwalk-like viruses Total Viral food borne
 23,000,000 30,883,391
 Rotavirus Total Microbial food
 3,900,000 borne incidence
 38,629,64
Astrovirus
 3,900,000
Hepatitis A
83,391 CDC

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 Hepatitis A
Diagnosis
Clinical manifestions
 Viral antigens
Immunoelectron microscopy
RIA
ELISA
Immune Adherence hemagglutination (old
method)
Viral antibodies
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 Hepatitis A
Control
 No specific control
Improve hygiene and sanitation
Human immunoglobulin
2 IU anti Hepatitis A /kg body weight
HAV vaccines in clinical field trials

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 Hepatitis B

“Serum hepatitis”
HBV

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 Hepatitis B
Clinical Manifestations
typical viral hepatitis symptoms
4-26 week incubation period
more severe than HAV
CHRONIC PERSISTENT HEPATITIS
CHRONIC ACTIVE HEPATITIS

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 Hepatitis B
Structure
 Hepadnavirus
 dsDNA, circular, 3200 nucleotides
enveloped icosahedral virus
42 nm

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 Australia antigen
“Dane particle”
small pelomorphic particles 20-22nm
tubular forms
excess viral capsids released into blood
stream

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 3 forms of HBV

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 Dane Particles

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 Hepatitis B
Host Defenses
Cell mediated Immunity
important
for recover in acute phase
autoimmune liver damage in chronic infections

Humoral Immunity
not
always protective
HBsAg for Vaccines

Interferon
notdetected during infection
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exogenous application effective
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 Hepatitis B
Epidemiology
Parenterally ie via blood, saliva, menstrual
and vaginal discharges, semen and breast
milk
infected blood and blood products
sexual contact
perinatally from mother to child

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 Hepatitis B
Prevalence
AREA HBsAg anti HBsAg
Western Europe 0.2-0.5% 4-6%
USA
Eastern Europe 2-7 % 20-55%
USSR
China 8-20 % 70-95%
Asia
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 Hepatitis B
Diagnosis
Electron microscopy
Viral DNA polymerase
Viral DNA probes
Serology

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 Hepatitis B
Serology
Hepatitis B surface antigen- HBsAg
 10 subtypes
Hepatitis B core antigen- HBsCAg
Soluble core associated antigen HBeAg
Corresponding antibodies to
each antigen occur

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 Hepatitis B
Control
No specific control
Passive Immunization
 HBV immunoglobulin
250-500 IU within 48 hours
neonates of infected mothers -immediately after
birth
Active Immunization
HBsAg
recombinant DNA in yeast 8/27/2019
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 HBV & Cancer

1. Transformation of the cell by virus

2. Helper virus if the transforming virus is
defective
3. Co-carcinogen, chemical, cigarette smoke

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 Transformed cells

lose contact inhibition

continue to divide
form random aggregations
can become invasive
Not warts: Papovavirus

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 Primary Hepatocellular Carcinoma

Highest incidence:
Central Africa
Southeast China
Pacific Islands, Borneo, Sarawak, Taiwan

Icteric symptoms:
jaundice, dark urine, pale stools
 Global 250,000- 1,000,000 deaths /year
 U.S.A. 5000 deaths / year
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 Acute HBV & Cancer

Acute Hepatitis B
90% 1%
Resolution
Fulminant Hepatitis
Resolution Chronic Active
Asymptomatic Hepatitis
Carrier Chronic
Cirrhosis
50%
Hepatic
Extrahepatic Cell Carcinoma
Disease
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 Hepatitis C

HCV
Non -A Non-B

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 Hepatitis C
Clinical Manifestations
resembles HBV
persistent carrier state
50% of patients have chronic liver damage
associated with hepatocellular carcinoma

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 Hepatitis C
is probably caused by several
different viruses

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 Hepatitis C
Epidemiology
 in USA causes 90% of post transfusion
hepatitis
Mother to infant transmission

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 Hepatitis C
Diagnosis
C100-3 recombinant viral antigen
anti c100-3 marker of chronic infection

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 Hepatitis A Hepatitis B Hepatitis C
HAV HBV HCV

Structure RNA DNA HBV

Cultured in cells yes no no

Epidemiology endemic & epidemic endemic endemic

oral/fecal, blood/serum, blood/serum,

Transmission close contact intimate contact
water & food

Incubation period 2-7 weeks 1-6 months 2-8 weeks

Symptoms fever, G-I tract disorder fever, rash, arthritis similar to HBV

Jaundice 1 case in 10 common common

Onset acute/short gradual/chronic acute/chronic

Vaccine not available yes not available

Diagnostic tests yes yes yes

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 Hepatitis D

HDV

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 Hepatitis D

Dependovirus, it is defective and cannot

produce infection unless the cell is also
infected with HBV.
Viroid - a naked strand of RNA that enters
the cell in piggy-back fashion.

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 Hepatitis D
Clinical Manifestations
Dual infection is more severe than HBV
fulminating hepatitis
severe rapidly progressive hepatitis
severe exacerbations

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 Hepatitis D
Structure
35-37 nm virus particle
shares coat protein of HBV
 small RNA genome
one serotype

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 Hepatitis D
Epidemiology
 hemophiliacs and IV drug users
Contaminated blood and blood products

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 Geographic distribution of HDV

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 Hepatitis D
Diagnosis
Clinical manifestations
 Delta antigen
Immunofluorescence
RIA
ELISA

Anti delta antigen

same as above

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 Hepatitis E Virus

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 Hepatitis E

fecal/oral route
predominantly found in developing
countries but is world wide.
symptoms similar to HAV but mortality 1-
2% (ten times that of Hepatitis A).
epidemics - India, Pakistan, Nepal, Burma,
North Africa and Mexico.
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