Viral

Viral Hepatitis
Hepatitis

Hugh B. Fackrell

Filename: Hepatite.ppt

10/28/21
1
 Hepatitis
Hepatitis Virus
Virus Outline
Outline

Definitions
Classification
Structure
Multiplication
Clinical manifestations
Epidemiology
Diagnosis
Control
10/28/21
2 Baron’s Web Site
 Hepatitis
Hepatitis

an ancient disease, the etiology has only

recently (50 yrs.) been revealed.

10/28/21
3
 Hepatitis
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

10/28/21
4
 Bilirubin
Bilirubin

Bilirubin: greenish-yellow pigment

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

10/28/21
5
 Types
Types of
of Jaundice
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
10/28/21
6
 Jaundice
Jaundice of
of the
the Newborn
Newborn

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

10/28/21
7
 Hepatitis
Hepatitis symptoms
symptoms

Swelling and
tenderness of liver
Jaundice -yellow tinge
in the skin and eyes
dark urine
transaminase, alkaline
phosphatase levels
increased
10/28/21
8
 Viral
Viral Hepatitis
Hepatitis

Liver infection caused by several

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

10/28/21
9
 Hepatitis
Hepatitis types
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”

10/28/21
10
 Hepatitis
Hepatitis A
A

“Infectious hepatitis”
“Epidemic hepatitis”
HAV

10/28/21
11
 Hepatitis
Hepatitis A
A
Clinical
Clinical manifestations
manifestations
asymptotic or anicteric in children
3-5 week incubation period
liver inflammation
malaise - flu like symptoms
self limiting
low mortality

10/28/21
12
 Hepatitis
Hepatitis A
A
Structure
Structure
Picornavirus
Only one serotype
Enterovirus type 72
27-29 nm icosahedral
 ssRNA

10/28/21
13
 Hepatitis
Hepatitis A
A
Host
Host Defenses
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
 lasts many years
10/28/21
14
 Hepatitis
Hepatitis A
A
Epidemiology
Epidemiology
Global distribution- underreported
Fecal-oral route,
 person to person
 water
Overcrowding & poor sanitation
 Infected food handlers common vector

10/28/21
15
 Annual
Annual Incidence
Incidence Viral
Viral food
food
borne
borne diseases
diseases
 Norwalk-like viruses  Total Viral food borne
 23,000,000 30,883,391

 Rotavirus
 3,900,000  Total Microbial food borne
 Astrovirus incidence
 3,900,000
 38,629,64

Hepatitis A
CDC
 83,391
10/28/21
16
 Hepatitis
Hepatitis A
A
Diagnosis
Diagnosis
Clinical manifestions
 Viral antigens
 Immunoelectron microscopy
 RIA
 ELISA
 Immune Adherence hemagglutination (old
method)
Viral antibodies
10/28/21
17
 Hepatitis
Hepatitis A
A
Control
Control
 No specific control
Improve hygiene and sanitation
Human immunoglobulin
 2 IU anti Hepatitis A /kg body weight
HAV vaccines in clinical field trials

10/28/21
18
 Hepatitis
Hepatitis B
B

“Serum hepatitis”
HBV

10/28/21
19
 Hepatitis
Hepatitis B
B
Clinical
Clinical Manifestations
Manifestations
typical viral hepatitis symptoms
4-26 week incubation period
more severe than HAV
CHRONIC PERSISTENT HEPATITIS
CHRONIC ACTIVE HEPATITIS

10/28/21
20
 Hepatitis
Hepatitis B
B
Structure
Structure
 Hepadnavirus
 dsDNA, circular, 3200 nucleotides
enveloped icosahedral virus
42 nm

10/28/21
21
 Australia
Australia antigen
antigen
“Dane
“Dane particle”
particle”
small pelomorphic particles 20-22nm
tubular forms
excess viral capsids released into blood
stream

10/28/21
22
 33 forms
forms of
of HBV
HBV

10/28/21
23
 Dane
Dane Particles
Particles

10/28/21
24
 Hepatitis
Hepatitis B
B
Host
Host Defenses
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 detected during infection
 exogenous application effective
10/28/21
25
 Hepatitis
Hepatitis B
B
Epidemiology
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

10/28/21
26
 Hepatitis
Hepatitis B
B
Prevalence
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
10/28/21
27
 Hepatitis
Hepatitis B
B
Diagnosis
Diagnosis
Electron microscopy
Viral DNA polymerase
Viral DNA probes
Serology

10/28/21
28
 Hepatitis
Hepatitis B
B
Serology
Serology
Hepatitis B surface antigen- HBsAg
 10 subtypes
Hepatitis B core antigen- HBsCAg
Soluble core associated antigen HBeAg
Corresponding antibodies to
each antigen occur

10/28/21
29
 Hepatitis
Hepatitis B
B
Control
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
10/28/21
30
 HBV
HBV &
& Cancer
Cancer
1. Transformation of the cell by virus
2. Helper virus if the transforming virus is
defective
3. Co-carcinogen, chemical, cigarette smoke

10/28/21
31
 Transformed
Transformed cells
cells

lose contact inhibition

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

10/28/21
32
 Primary
Primary Hepatocellular
Hepatocellular Carcinoma
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
10/28/21
33
 Acute
Acute HBV
HBV &
& Cancer
Cancer

Acute Hepatitis B
90% 1%
Resolution
Fulminant Hepatitis
Resolution Chronic Active
Asymptomatic Hepatitis
Carrier Chronic
Cirrhosis
50%
Hepatic
Extrahepatic Cell Carcinoma
Disease
10/28/21
34
 Hepatitis
Hepatitis C
C

HCV
Non -A Non-B

10/28/21
35
 Hepatitis
Hepatitis C
C
Clinical
Clinical Manifestations
Manifestations
resembles HBV
persistent carrier state
50% of patients have chronic liver damage
associated with hepatocellular carcinoma

10/28/21
36
 Hepatitis
Hepatitis C
C
is
is probably
probably caused
caused by
by several
several
different
different viruses
viruses

10/28/21
37
 Hepatitis
Hepatitis C
C
Epidemiology
Epidemiology
 in USA causes 90% of post transfusion
hepatitis
Mother to infant transmission

10/28/21
38
 Hepatitis
Hepatitis C
C
Diagnosis
Diagnosis
C100-3 recombinant viral antigen
anti c100-3 marker of chronic infection

10/28/21
39
 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

10/28/21
40
 Hepatitis
Hepatitis D
D

HDV

10/28/21
41
 Hepatitis
Hepatitis D
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.

10/28/21
42
 Hepatitis
Hepatitis D
D
Clinical
Clinical Manifestations
Manifestations
Dual infection is more severe than HBV
fulminating hepatitis
severe rapidly progressive hepatitis
severe exacerbations

10/28/21
43
 Hepatitis
Hepatitis D
D
Structure
Structure
35-37 nm virus particle
shares coat protein of HBV
 small RNA genome
one serotype

10/28/21
44
 Hepatitis
Hepatitis D
D
Epidemiology
Epidemiology
 hemophiliacs and IV drug users
Contaminated blood and blood products

10/28/21
45
 Geographic
Geographic distribution
distribution of
of HDV
HDV

10/28/21
46
 Hepatitis
Hepatitis D
D
Diagnosis
Diagnosis
Clinical manifestations
 Delta antigen
 Immunofluorescence
 RIA
 ELISA
Anti delta antigen
 same as above

10/28/21
47
 Hepatitis
Hepatitis EE Virus
Virus

10/28/21
48
 Hepatitis
Hepatitis E
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.
10/28/21
49