Transcript Hepatitis B

25 Hepatitis Virus
Viral Hepatitis - Historical
Perspective
Enterically
E
transmitted
“Infectious” A
Viral
hepatitis
“Serum”
NANB
Parenterally
C transmitted
B D
F, G,
? other
Viral Hepatitis - Overview
Type of Hepatitis
A
Source of
virus
feces
Route of
transmission
Chronic
infection
Prevention
B
C
D
blood/
blood/
blood/
blood-derived blood-derived blood-derived
body fluids
body fluids
body fluids
E
feces
fecal-oral percutaneous percutaneous percutaneous fecal-oral
permucosal permucosal permucosal
no
pre/postexposure
immunization
yes
yes
yes
no
pre/post- blood donor
pre/post- ensure safe
exposure
screening;
exposure
drinking
immunization risk behavior immunization; water
risk behavior
modification
modification
HEPATITIS A VIRUS
HEPATITIS A VIRUS
• RNA Picornavirus
 Single serotype worldwide
 Acute disease and asymptomatic infection
• No chronic infection
 Protective antibodies develop in response to
infection - confers lifelong immunity
HEPATITIS A - CLINICAL
FEATURES
•Jaundice by
age group:
<6 yrs
6-14 yrs
>14 yrs
<10%
40%-50%
70%-80%
•Rare complications:
Fulminant hepatitis
Cholestatic hepatitis
Relapsing hepatitis
•Incubation period:
Average 30 days
Range 15-50 days
•Chronic sequelae:
None
EVENTS IN HEPATITIS A VIRUS INFECTION
Clinical illness
Infection
ALT
Response
IgM
IgG
Viremia
HAV in stool
0
1
2
3
4
5
6
Week
7
8
9
10
11
12
13
CONCENTRATION OF HEPATITIS A VIRUS
IN VARIOUS BODY FLUIDS
Body Fluids
Feces
Serum
Saliva
Urine
100
102
104
106
Infectious Doses per mL
108
1010
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)
• Blood exposure (rare)
(e.g., injection drug use, rarely by
transfusion)
PREVENTING HEPATITIS A
• Hygiene (e.g., hand washing)
• Sanitation (e.g., clean water sources)
• Hepatitis A vaccine (pre-exposure)
attenuated virus or inactivated virus
• Immune globulin (pre- and post-exposure)
Hepatitis E Virus
•HEV is a 30-32nm non-enveloped particle containing a
s/s (+)sense RNA genome of ~7.5Kb.
•Genetic organization similar (not identical) to
Caliciviruses:
Hepatitis E - Clinical
Features
• Incubation period:
• Case-fatality rate:
Average 40 days
Range 15-60 days
Overall, 1%-3%
Pregnant women, 5%25%
• Illness severity:
Increased with age
• Chronic sequelae:
None identified
Hepatitis E Virus Infection
Typical Serologic Course
Symptoms
ALT
IgG anti-HEV
Titer
IgM anti-HEV
Virus in stool
0
1
2
3
4
5
6
Weeks after
Exposure
7
8
9
1
0
1
1
1
2
1
3
Hepatitis E Epidemiologic Features
• Most outbreaks associated with
fecally contaminated drinking water
• Minimal person-to-person
transmission
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?
Hepatitis B - Clinical
Features
• Incubation period:
Average 60-90 days
Range 45-180 days
• Clinical illness (jaundice): <5 yrs, <10%
³5 yrs, 30%-50%
• Acute case-fatality rate:
• Chronic infection:
0.5%-1%
<5 yrs, 30%-90%
³5 yrs, 2%-10%
(350m )
carrier state
• Premature mortality from
chronic liver disease:
15%-25%
Acute Viral Hepatitis
Source: CDC
Hepatitis B Virus
secreted sphere
hepatitis B virion
secreted filament
• Baruch Blumberg,
1963: ‘Australian
antigen - Au'.
• 1967: Au was a viral
antigen = HBsAg
(surface antigen)
• Dane, 1970:
Discovered 42nm
'Dane particles‘
HBcAg (core antigen).
• 1973: HBeAg
discovered
(endogenous antigen
= a truncated version
of HBcAg).
• spherical,
• enveloped (? lipid-containing,
detergent disrupted ?)
• 42-47nm diameter
• d/s DNA
• an RNA-dependent DNA
polymerase (i.e. reverse
transcriptase)
• family
Hepadnaviridae
HBV genome organization
two uneven strands
of DNA:
(-)sense strand:
3.0 - 3.3kb
(+)sense strand:
1.7 - 2.8kb
The HBV infectious cycle
Reverse transcription
P protein
Capsid
protein
ER/IC
e
Golgi
cap
RNA pregenome
RNA
ccc-DNA
Precore, L, M, S + X
proteins
four open reading
frames (ORFs) :
S,C,P,X
• S – HBsAg
• C – HBcAg
C + preC – HBeAg
• P – polymerase
• X – HBxAg (a
transcriptional
transactivator)
HBsAg & anti-HBs
• HBsAg is an envelope protein & an poor
immunogen -------- replication
• recovery of acute HBV infection is
characterized by HBsAg/anti-HBs
seroconversion
• passively acquired anti-HBs protects
individuals from infection with HBV
• Anti-HBs is not strictly a ‘neutralizing’
antibody
HBcAg & anti-HBc
• HBcAg is not detectable in the sera of
some patients.
• immunogen
• IgM anti-HBc – virus replication, acute
infection, transient response
• IgG anti-HBc – do not protect individuals,
chronic infections, alst for a long time
HBeAg & anti-HBe
• HBeAg is produced when virus is
replicating.
• HBeAg is correlated strongly with the
detection of viral DNA, virons and the
viral DNA polymerase in the serum.
• The disappearace of HBeAg and
replacement with anti-Hbe indicates that
the patient is responding to the infection
and will clear HBsAg.
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Symptoms
anti-HBe
HBeAg
Total anti-HBc
Titer
HBsAg
0
4
8
anti-HBs
IgM anti-HBc
12 16 20 24 28 32 36
Weeks after
52
100
Progression to Chronic Hepatitis B Virus
Infection
Typical Serologic Course
Acute
(6 months)
Chronic
(Years)
HBeAg
anti-HBe
HBsAg
Total antiHBc
Titer
IgM anti-HBc
0 4 8 12 16 20 24 28 32 36
Weeks after Exposure
52
Years
Summary
Hepatitis B Lab Tests (1)
• HBV: Hepatitis B virus.
• HBsAg: Hepatitis B surface antigen. Marker of
infectivity when found in serum.
• anti-HBs: Antibody to HBsAg. Marker of immunity
when found in serum.
• HBcAg: Hepatitis B core antigen. No commercial test
available for this.
• anti-HBc: Antibody HBcAg. Marker of past or current
infection.
Hepatitis B Lab Tests (2)
• IgM anti-HBc: IgM is an antibody subclass of
anti-HBc. Indicates recent infection with HBV
(<4-6 mos.).
• IgG anti-HBc: IgG is a subclass of anti-HBc. Indicates
“older” infection with HBV.
• HBeAg: Hepatitis B “e” antigen. Can only be present if
HBsAg is positive. Marker of high degree of infectivity.
• Anti-HBe: Antibody to “e” antigen. May be present in
infected or immune person.
Interpretation of Hepatitis B Panel
HBsAg
antiHBc
antiHBs
negative
negative
negative
susceptible
HBsAg
antiHBc
antiHBs
negative
positive
positive
immune due to natural infection
HBsAg
antiHBc
antiHBs
negative
negative
positive
immune due to vaccine
HBsAg
antiHBc
IgM antiHBc
antiHBs
positive
positive
positive
negative
HBsAg
antiHBc
IgM antiHBc
antiHBs
positive
positive
negative
negative
HBsAg
antiHBc
antiHBs
negative
positive
negative
acutely infected
chronically
infected
four possible interpretations
(see next slide)
Four possible interpretations
of isolated antiHBc positive
1. May be recovering from acute HBV infection.
2. May be distantly immune and test not sensitive
enough to detect very low level of anti-HBs in serum.
3. May be susceptible with a false positive anti-HBc.
4. May be undetectable level of HBsAg present in the
serum and the person is actually a carrier.
Concentration of Hepatitis B
Virus
in Various Body Fluids
High
Moderate
blood
semen
serum
vaginal fluid
wound exudates
saliva
Low/Not
Detectable
urine
feces
sweat
tears
breastmilk
Main Ways to Get Hepatitis B
Having sex without condoms with someone who
has hepatitis B
Sexual
Being born to a mother who has hepatitis B
Perinatal
Sharing needles and syringes
Parenteral
You can pass hepatitis B to others if you have just
gotten the virus (acute hepatitis) or if you are a
carrier of the virus (chronic hepatitis).
How does a baby get hepatitis B
from mother?
• If you have hepatitis B and a tiny bit of your
blood gets inside your baby at birth.
CONTROL
Passive immunization
• Hyperimmune
hepatitis B
immunoglobulin
HBIG
Active immunization
• Vaccine
HBsAg
Hepatitis B can be prevented!
If you have never had hepatitis B,
you can get 3 shots . . .
1
2
3
. . . and get long lasting protection.
Baby Shots
for Hepatitis B
if the mother has Hepatitis B
1 - 2 months old
Birth
Hepatitis B
Vaccine
+
Hepatitis B
Vaccine
H-BIG
6 months old
Hepatitis B
Vaccine
Hepatitis D (Delta) Virus
d antigen
HBsAg
RNA
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
Hepatitis D Virus
Modes of Transmission
• Percutanous
exposures
–injecting drug use
• Permucosal
exposures
–sex contact
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
Hepatitis C
Flaviviridae
a positive-sense RNA molecule 9.5kb in length
Features of Hepatitis C Virus
Infection
Incubation period
Acute illness (jaundice)
Case fatality rate
Chronic infection
Chronic hepatitis Agerelated
Cirrhosis
Mortality from CLD
Average 6-7 weeks
Range 2-26 weeks
Mild (<20%)
Low
60%-85%
10%-70%
<5%-20%
1%-5%
Serologic Pattern of Acute HCV Infection
with Recovery
antiHCV
Symptoms +/-
Titer
HCV RNA
ALT
Normal
0
1
2
3
4
Months
5
6
1
2
3
Years
Time after Exposure
4
Serologic Pattern of Acute HCV Infection with
Progression to Chronic Infection
antiHCV
Symptoms +/-
Titer
HCV RNA
ALT
Normal
0
1
2
3
4
Months
5
6
1
2
3
Years
Time after Exposure
4
HCV Prevention and Control
Reduce or Eliminate Risks for
Acquiring HCV Infection
• Screen and test donors
• Virus inactivation of plasma-derived products
• Risk-reduction counseling and services
– Obtain history of high-risk drug and sex behaviors
– Provide information on minimizing risky behavior,
including referral to other services
– Vaccinate against hepatitis A and/or hepatitis B
• Safe injection and infection control practices
Preventing HCV Transmission to
Others
Avoid Direct Exposure to Blood
• Do not donate blood, body organs, other
tissue or semen
• Do not share items that might have blood on
them
– personal care (e.g., razor, toothbrush)
– home therapy (e.g., needles)
• Cover cuts and sores on the skin
HCV Counseling
Other Transmission Issues
• HCV not spread by kissing, hugging,
sneezing, coughing, food or water, sharing
eating utensils or drinking glasses, or casual
contact
• Do not exclude from work, school, play,
child-care or other settings based on HCV
infection status