Download Hepatitis Viruses

Viral Hepatitis
Hugh B. Fackrell
Filename: Hepatite.ppt
4/29/2017
1
Hepatitis Virus Outline
2
Definitions
Classification
Structure
Multiplication
Clinical manifestations
Epidemiology
Diagnosis
Control
Baron’s Web Site
4/29/2017
Hepatitis
an ancient disease, the etiology has only
recently (50 yrs.) been revealed.
4/29/2017
3
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
4/29/2017
4
Bilirubin
Bilirubin: greenish-yellow pigment
accumulates in the blood and tissues
Jaundice 
yellow tinge in the skin and eyes
caused
by bilirubin
4/29/2017
5
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
4/29/2017
6
Jaundice of the Newborn
Premature infants
bilirubin increases from birth
peaks at one week
caused by
1:excessive
hemolysis
2:immature liver function
4/29/2017
7
Hepatitis symptoms
8
Swelling and
tenderness of liver
Jaundice -yellow
tinge in the skin and
eyes
dark urine
transaminase, alkaline
phosphatase levels
increased
4/29/2017
Viral Hepatitis
Liver infection caused by several
UNRELATED VIRUSES
Inflammation and necrosis of the liver
50% of HAV & HBV are subclincal
4/29/2017
9
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”
4/29/2017
10
Hepatitis A
“Infectious hepatitis”
“Epidemic hepatitis”
HAV
4/29/2017
11
Hepatitis A
Clinical manifestations
asymptotic or anicteric in children
3-5 week incubation period
liver inflammation
malaise - flu like symptoms
self limiting
low mortality
4/29/2017
12
Hepatitis A
Structure
Picornavirus
Only one serotype
Enterovirus type 72
27-29 nm icosahedral
 ssRNA
4/29/2017
13
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
14
IgM
peaks 60-80 days
lasts many years
4/29/2017
Hepatitis A
Epidemiology
Global distribution- underreported
Fecal-oral route,
person

to person
water
Overcrowding & poor sanitation
 Infected food handlers common vector
4/29/2017
15
Annual Incidence Viral food
borne diseases
Norwalk-like viruses Total Viral food borne
30,883,391
 23,000,000
Total Microbial food
 Rotavirus
borne incidence
 3,900,000
Astrovirus


38,629,64
3,900,000
Hepatitis A
83,391
CDC
4/29/2017
16
Hepatitis A
Diagnosis
Clinical manifestions
 Viral antigens
Immunoelectron
microscopy
RIA
ELISA
Immune Adherence
hemagglutination (old
method)
Viral antibodies
4/29/2017
17
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
4/29/2017
18
Hepatitis B
“Serum hepatitis”
HBV
4/29/2017
19
Hepatitis B
Clinical Manifestations
typical viral hepatitis symptoms
4-26 week incubation period
more severe than HAV
CHRONIC PERSISTENT HEPATITIS
CHRONIC ACTIVE HEPATITIS
4/29/2017
20
Hepatitis B
Structure
 Hepadnavirus
 dsDNA, circular, 3200 nucleotides
enveloped icosahedral virus
42 nm
4/29/2017
21
Australia antigen
“Dane particle”
small pelomorphic particles 20-22nm
tubular forms
excess viral capsids released into blood
stream
4/29/2017
22
3 forms of HBV
4/29/2017
23
Dane Particles
4/29/2017
24
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
not
25
detected during infection
exogenous application effective
4/29/2017
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
4/29/2017
26
Hepatitis B
Prevalence
AREA
Western Europe
USA
Eastern Europe
USSR
China
Asia
HBsAg
0.2-0.5%
anti HBsAg
4-6%
2-7 %
20-55%
8-20 %
70-95%
4/29/2017
27
Hepatitis B
Diagnosis
Electron microscopy
Viral DNA polymerase
Viral DNA probes
Serology
4/29/2017
28
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
4/29/2017
29
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
30
recombinant
DNA in yeast
4/29/2017
HBV & Cancer
1. Transformation of the cell by virus
2. Helper virus if the transforming virus is
defective
3. Co-carcinogen, chemical, cigarette smoke
4/29/2017
31
Transformed cells
lose contact inhibition
continue to divide
form random aggregations
can become invasive
Not warts: Papovavirus
4/29/2017
32
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
4/29/2017
33
Acute HBV & Cancer
Acute Hepatitis B
90%
1%
Resolution
Fulminant Hepatitis
Resolution
Asymptomatic
Carrier
Chronic Active
Hepatitis
Chronic
50%
Extrahepatic
Disease
Cirrhosis
Hepatic
Cell Carcinoma
4/29/2017
34
Hepatitis C
HCV
Non -A Non-B
4/29/2017
35
Hepatitis C
Clinical Manifestations
resembles HBV
persistent carrier state
50% of patients have chronic liver damage
associated with hepatocellular carcinoma
4/29/2017
36
Hepatitis C
is probably caused by several
different viruses
4/29/2017
37
Hepatitis C
Epidemiology
 in USA causes 90% of post transfusion
hepatitis
Mother to infant transmission
4/29/2017
38
Hepatitis C
Diagnosis
C100-3 recombinant viral antigen
anti c100-3 marker of chronic infection
4/29/2017
39
Hepatitis A
HAV
Hepatitis B
HBV
Hepatitis C
HCV
Structure
RNA
DNA
HBV
Cultured in cells
yes
no
no
Epidemiology
endemic & epidemic
endemic
endemic
Transmission
oral/fecal,
water & food
blood/serum,
close contact
blood/serum,
intimate contact
2-7 weeks
1-6 months
2-8 weeks
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
not available
yes
not available
yes
yes
yes
Incubation period
Symptoms
Vaccine
Diagnostic tests
4/29/2017
40
Hepatitis D
HDV
4/29/2017
41
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.
4/29/2017
42
Hepatitis D
Clinical Manifestations
Dual infection is more severe than HBV
fulminating hepatitis
severe rapidly progressive hepatitis
severe exacerbations
4/29/2017
43
Hepatitis D
Structure
35-37 nm virus particle
shares coat protein of HBV
 small RNA genome
one serotype
4/29/2017
44
Hepatitis D
Epidemiology
 hemophiliacs and IV drug users
Contaminated blood and blood products
4/29/2017
45
Geographic distribution of HDV
4/29/2017
46
Hepatitis D
Diagnosis
Clinical manifestations
 Delta antigen
Immunofluorescence
RIA
ELISA
Anti delta antigen
same
as above
4/29/2017
47
Hepatitis E Virus
4/29/2017
48
Hepatitis E
fecal/oral route
predominantly found in developing
countries but is world wide.
symptoms similar to HAV but mortality 12% (ten times that of Hepatitis A).
epidemics - India, Pakistan, Nepal, Burma,
North Africa and Mexico.
4/29/2017
49