Transcript CDC-Power Point Presentation Hepatitis A through E

The ABC’s of Hepatitis
Ian Williams, PhD, MS
Division of Viral Hepatitis
Centers for Disease Control and Prevention
Viral Hepatitis – Historical Perspective
“Infectious”
Viral hepatitis
“Serum”
A
Enterically
E
transmitted
NANB
B D
Parenterally
C
transmitted
F, G,
? other
Classification of Hepatitis Viruses
Virus
Family
DNA or RNA
Envelope
HAV
Picornaviridae
RNA*
no
HBV
Hepadnaviridae
DNA**
yes
HCV
Flaviviridae
RNA*
yes
HDV
Deltavirus (genus)
RNA***
yes
RNA*
no
HEV
?
(Previously classified as a
calicivirus)
*linear, single strand; ** circular, double strand; *** circular, single strand
Basic Features of Hepatitis Viruses
Incubation
Period*
Chronic
Infection
Virus
Transmission
A
fecal-oral
B
parenteral
8-12 (6-24)
Yes
C
parenteral
6-9 (2-24)
Yes
D
parenteral
? (2-10)
Yes
E
fecal-oral
* Weeks
4 (2-6)
4-5 (2-9)
No
No
Acute Viral Hepatitis, United States,
1991-1998
63%
28%
8%
1%
Source: Sentinel Counties Study, CDC
Hepatitis A
Hepatitis B
Hepatitis C
Non-ABCDE
Mechanism of Injury
•
Hepatotropic viruses
•
Acute infection:
direct cytotoxicity vs. immune response to
infection vs. combination of the two
•
Chronic infection:
immune response probably more important
Clinical Manifestations of
Acute Viral Hepatitis
Asymptomatic
Symptomatic
Fulminant liver failure
and death
Typical Signs and Symptoms
•
•
•
•
•
Fever
Malaise
Anorexia
Nausea
Vomiting
• Jaundice
• Scleral icterus
• Abdominal/RUQ pain
• Hepatomegaly
• Arthritis
Laboratory Findings in Acute Viral Hepatitis
Laboratory indicators of liver pathology
• Elevated ALT (SGPT) and AST (SGOT)
• Elevated bilirubin
• Elevated alkaline phosphatase
Laboratory indicators of infection
• Increased WBC
All non-specific with regard to making
an etiologic diagnosis
Differential Diagnosis of Acute Hepatitis
Viral infections
hepatitis A, B, C, D, and E,
CMV, EBV, HSV, VZV, yellow fever
Bacterial infections
typhoid fever, Q fever, RMSF,
leptospirosis, secondary syphillis,
sepsis
toxocariasis, liver flukes
Parasitic infections
Toxins
ASA, acetaminophen, INH, rifampin,
oral contraceptives, anti-seizure meds,
carbenicillin, sulfonamides
Alcohol, carbon tetrachloride
Autoimmune diseases
Autoimmune hepatitis, SLE
Drugs
Immunologic Markers Used for
Serologic Diagnosis
Immune globulin of the M sublcass (IgM):
• Produced in early infection
Immune globulin of the G subclass (IgG):
• Produced in later infection
Total immune globulin (Total Ig):
• Combination of IgM and IgG
• Early infection - primarily IgM
• Late infection - primarily IgG
Hepatitis A Virus (HAV)
Clinical Features of Hepatitis A
Incubation period
Mean:28-30 days
Range:2-6 weeks
Jaundice
<6 years:
10%
6-14 years: 40-50%
>14 years: 70-80%
Case fatality
Overall: 0.3%
>50 years: 1.8%
Chronic infection
No
Transmission of HAV
Virus transmitted from person to person
 Primarily through fecal-oral route

– short period of viremia
– occasional bloodborne transmission
Virus shed in feces of infected persons (both
symptomatic and asymptomatic persons)
 Greatest period of communicability: 2 weeks
before onset of jaundice
 Virus in environment for months

Modes of Transmission of HAV
 Close
personal contact
- household
 Ingestion
- sexual
of contaminated food and water
- Fresh produce
- ice
- food contaminated after cooking
 Blood
exposure (rare)
- blood transfusion -injection drug use
Reported Risk Factors for Hepatitis A
in the United States
Household or sexual contact (12%)
Unknown* (51%)
Day care related (11%)
Male homosexual activity (7%)
Injection drug use (14%)
Travel (4%)
* Most "unknowns" probably related to person-to-person transmission
Source: Sentinel Counties Surveillance System for Acute Viral Hepatitis, CDC
45
40
35
30
25
20
15
10
5
0
2000
98
96
94
92
1990
88
86
84
82
1980
78
76
74
72
1970
68
66
64
62
1960
58
56
54
52
Reported cases per 100,000
population
Reported Incidence of Hepatitis A
United States (1952-2001)
Source: CDC
Year
Estimated Incidence of Acute Hepatitis A in the
United States (1982-2001)
Number
Estimated Acute Cases
Estimated Acute Infections
400,000
350,000
300,000
250,000
200,000
150,000
100,000
50,000
0
1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000
Year
Immune Globulin (IG)



Prepared from pooled human plasma
Mechanism of action: passive transfer
of neutralizing antibodies
Prevents infection or clinical
expression of disease
Prevention of Hepatitis A with IG
Pre-Exposure Prophylaxis
• Protection lasts 3-5 months
• Used for travelers
Post-Exposure Prophylaxis
• Must be given within 14 days of exposure
• Used for household and sexual exposures
• Sometimes used for common source
exposures (e.g., infected food handler)
Prevention of Hepatitis A with
Hepatitis A Vaccine
 Used
for pre-exposure prophylaxis
 Given as 2-dose series
 Licensed for use for persons >2 years old
 Duration of protection: at least 20 years –
possibly lifelong
 Unresolved issues:
– use for post-exposure prophylaxis
– use in community-wide outbreaks
Recommendations for Hepatitis A
Vaccination
 Travelers
to HAV endemic countries
 Homosexual and bisexual men
 Drug users (IDU and other street drugs)
 Persons with chronic liver disease
(disease more server in these persons –
not necessarily at higher risk)
 Children living in states with high rates
of hepatitis A
Transmission of Bloodborne Viral Infections
Route

Percutaneous
 Apparent
 Inapparent
 Permucosal
Mode
injection drug use
needle stick injury
blood/ serous fluid
sex
perinatal
Relative Transmission Efficiency of
Bloodborne Viral Infections
HBV
HCV
HIV
Injection drug use
+++
++++
++
Sexual
+++
+
++
Perinatal
++++
+
++
Occupational
+++
+/-
+/-
Risk Factors for Transmission of
Hepatitis Viruses and HIV
Proportion of Infections
Risk Factor
HBV
HCV
HIV
Injection drug use
14%
60%
31%
MSM
15%
1%
47%
Heterosexual partners
40%
20%
10%
Transfusion
rare
Past
7- 20%
Past
2%
Occupational
5-7%
(past)
<<1%
<<1%
No Identified Risk
30%
10%
9%
Disease Burden from Bloodborne
Viral Infections
Outcome
Chronic infections
New infections /yr
Deaths /yr
HBV
HCV
HIV
~1.2
~2.7
~0.8
(million)
(million)
(million)
~120,000
~40,000
~40,000
5,000
8,000
18,000
Hepatitis B Virus (HBV)
Clinical Features of Hepatitis B
Incubation period
Average: 60-90 days
Range: 45-180 days
Clinical illness (jaundice) < 5 years: <10%
>5 years: 30-50%
Case-fatality rate
0.5-1.0%
Chronic infection
YES
<5 years: 30-90%
5 years: 6-10%
100
100
80
80
Chronic Infection
60
60
40
40
20
20
Symptomatic Acute Hepatitis B
0
Birth
1-6 months
7-12 months
Age at Infection
1-4 years
0
>5 years
Symptomatic Infection (%)
Chronic Infection (%)
Outcome of HBV Infection by
Age at Infection
Outcome of HBV Infection
Liver cancer
and cirrhosis
Chronic infection
Asymptomatic
acute hepatitis B
Resolved & immune
Asymptomatic
carrier
Infection
Liver cancer
and cirrhosis
Chronic infection
Symptomatic
acute hepatitis B
Asymptomatic
carrier
Resolved & immune
Chronic HBV Infection, Vietnam
Geographic Distribution of Chronic
HBV Infection
HBsAg Prevalence
>=8% - High
2-7% - Intermediate
<2% - Low
Concentration of HBV in Body Fluids
High
blood
serum
wound exudate
Moderate
semen
vaginal fluid
saliva
Low/not
Detectable
urine
feces
sweat
tears
breast milk
Modes of Transmission of HBV



Percutaneous and permucosal – e.g.,
IDU, needle stick injuries
Sexual – homosexual and
heterosexual
Perinatal – From mother to child
during labor and delivery (in utero
transmission rare)
Reported Risk Factors for Acute
Hepatitis B in the U.S. (1991-2000)
IDU (20%)
MSM (12%)
Other1 (5%)
Heterosexual (43%)
1
Unrecognized (14%)
Other: Household contact, institutionalization, hemodialysis, blood transfusion, occupational exposure
Source: Sentinel Counties Study of Acute Viral Hepatitis, CDC
Who is at Risk for HBV Infection?










High-risk heterosexual men and women
Sexually active homosexual men
Injection drug users
Health care workers
Household and sex partners of persons with chronic infection
Hemodialysis patients
Recipients of blood products
Clients and employees of institution for developmentally
disabled
Families of adoptees from HBV endemic countries
Inmates of correctional facilities
High-Risk Heterosexual Men & Women




>1 sex partner in the past 6 months
STD clinic patients
Recently acquired STD
Commercial sex workers
HBV Prevalence Among Various
Risk Groups
General population
(4.9%)
>10 sex partners
(6%)
>50 sex partners
(12%)
MSM
(20-40%)
IDU
(60-80%)
0
20
40
60
80
100
Percent Infected (Anti-HBc positive)
Prevention of HBV Infection
Hepatitis B Immune Globulin (HBIG)
• Post-exposure prophylaxis
Hepatitis B Vaccine
• Pre-exposure prophylaxis
• Post-exposure prophylaxis
Hepatitis B Immune Globulin (HBIG)
Prepared from plasma containing high titers
anti-HBs
 Used for post-exposure prophylaxis to
prevent infection from:

- Perinatal exposure
- Sexual exposure
- Occupational exposure
Must be given soon after exposure to be
effective
 Does not protect against future exposures

Hepatitis B Vaccine

Primary component of vaccine is HBsAg
– HBsAg elicits devolvement of anti-HBs
– anti-HBs protective antibody
Worldwide, plasma-derived and recombinant
formulations available
 Only recombinant available in U.S.
 Given as a 3-dose series
 Highly immunogenic – seroconversion ~95%
 Protection long-lasting – booster doses of vaccine
not recommended

Elimination of HBV Transmission
in the United States
Current Strategy



Routine vaccination of infants
Routine vaccination of adolescents not
vaccinated in infancy
Vaccination of high-risk children,
adolescents, and adults
Coverage, %
HepB3, DTP3, and Hib3 Coverage,
Among 19-35 Month-Old Children, 1992-2000
100
90
80
70
60
50
40
30
20
10
0
DTP3
Hib3
Routine
HepB vaccination
recommended
1990
HepB3
1991
1992
1993
1994
1995
Year
1996
1997
1998
1999
2000
Reported Cases of Acute Hepatitis B in Children
United States, 1985-2000
1 to 4 yrs
5 to 9 yrs
Reported Cases
200
150
100
50
Routine
HepB vaccination
recommended
0
00
20
99
19
98
19
97
19
96
19
95
19
94
19
93
19
92
19
91
19
90
19
89
19
88
19
87
19
86
19
85
19
Year
Estimated Incidence of Acute Hepatitis B in the
United States (1982-2001)
Estimated Acute Cases
350,000
300,000
Vaccine
licensed
Estimated Acute Infections
Infant immunization
recommended
Number
250,000
200,000
150,000
100,000
50,000
0
1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000
Year
Features of
HCV Infection

Incubation period
Average, 6–7 wk
Range, 2–26 wk

Acute illness (jaundice)
Mild (20%–30%)

Persistent infection
75%–85%

Chronic hepatitis
70%

Immunity
No protective antibody
response identified
Risk of Fatal Outcome in Persons Who
Develop Hepatitis C Infection
Time
100
85%
Chroni
c
20%
Cirrhosis
85
80%
17 25%
15%
Resolv
e
15
75%
Stable
68
Courtesy of Seeff, LB and Alter, HJ.
Stabl
e
13
Mortality
4
Etiology of Chronic Liver Disease
United States
Birmingham, AL
CDC, unpublished data
HBV&
Cryptogenic Alcohol 3%
17%
HBV 11%
Other
5%
Harlem, NYC
Frieden et al. Hepatology 1999
HBV & Alcohol
6%
Other 6%
HCV 11%
Alcohol
24%
HCV 26%
HCV & Alcohol
14%
HCV & Alcohol
46%
Alcohol
29%
HBV, HCV
& Alcohol
2%
Prevalence of HCV Infection by Age
United States, 1988-1994
Average Prevalence = ~1.8%
Prevalence of Anti-HCV (%)
4
# Infected Nationwide = ~3.9 million
3
2
1
0
6–11
12–19 20–29 30–39 40–49 50–59 60–69 70–79
Age (yr)
Alter MJ. N Engl J Med. 1999;341:556 (NHANES III, 1988–1994).
80+
Prevalence of HCV Infection by Age
and Race, United States, 1988-1994
7
Anti-HCV+ (%)
6
Black
5
Mexican
American
4
3
White
2
1
0
6–11
12–19
20–29
30–39
40–49
50–59
Age (yr)
Alter MJ. N Engl J Med. 1999;341:556 (NHANES III, 1988–1994).
60–69
70+
Prevalence of HCV Infection by
Age and Gender, United States, 1988-1994
Percent Anti-HCV Positive
6
Males
5
4
Total
3
2
Females
1
0
6-11
12-19 20-29 30-39 40-49 50-59 60-69
Source: CDC, NHANES III
Age in Years
70+
HCV Infection - Estimates of Past Incidence
and Future Prevalence
140
Decline in cases among IDUs
Infections
per 100,000
120
100
80
Incidence
60
40
20
0
Prevalence
2.0%
Overall prevalence
1.5%
1.0%
Infected
20+ years
0.5%
0.0%
1960
1970
1980
1990
2000
2010
Source: Armstrong GL et al. Hepatology 2000;31
2020
2030
Future Hepatitis C Mortality and Costs



Future HCV-related mortality may double over the
next 10 to 20 years
$10.7 billion in direct medical care expenditures
$ 75.5 billion in societal (indirect) costs
Wong JB, et al. AJPH 2000; 90(10): 1562-1569.
Relative Importance of Risk Factors for
Remote and Recent HCV Infection
Remote (>15 yr ago)
Recent (<15 yr ago)
Injection Drug Use
Injection Drug Use
Transfusion
Unknown
Other*
Sexual
Transfusion
Sexual
*Nosocomial, occupational, perinatal
Unknown Other*
Posttransfusion Hepatitis, United States
Alter HJ and Houghton M. Hepatitis C virus and eliminating posttransfusion hepatitis. Nature Medicine 2000;6:1082-6.
Risk of HCV, HBV, and HIV Infection
Among Injection Drug Users
Baltimore 1983–1988
100
Seroprevalence (%)
HCV
80
HBV
60
40
HIV
20
0
0
6
12
18
24
30
36
42
48
Duration of Injecting (mo)
Garfein RS. Am J Public Health. 1996;86:655.
54
60
66
72
Risk of HCV Infection Among
Injection Drug Users
Seroprevalence (%)
100
Baltimore: 1983-1988
80
60
40
20
0
0
6
12
18
24
30
36
42
48
54
60
66
Duration of Injection (months)
Garfein RS Am J Public Health 1996; 86:655. Thorpe LE JID 2000;182:158894. Diaz T Am J Public Health 2001; 91(1): 23-30.
72
78
84
Sexual Transmission of HCV

Case-control, cross sectional studies
– infected partner, multiple partners, early sex, non-use
of condoms, other STDs, sex with trauma
– MSM no higher risk than heterosexuals

Partner studies
– low prevalence (1.5%) among long-term partners
– infections might be due to common percutaneous
exposures (e.g., unsafe injections, drug use)
– male to female transmission more efficient
– more indicative of sexual transmission
Sexual Transmission of HCV- II

Occurs, but efficiency is low
– Rare between long-term steady partners
– Factors that facilitate transmission between
partners unknown (e.g., viral titer, other STDs)

Accounts for 15-20% of acute and chronic
infections in the United States
– Sex is a common behavior
– Large chronic reservoir provides multiple
opportunities for exposure to potentially infectious
partners
Other Potential Exposures to Blood

No or insufficient data showing increased risk
– intranasal cocaine use, tattooing, body piercing,
acupuncture, military service

Limited number of studies showing associations
that cannot be generalized
– convenience or highly selected groups (mostly blood
donors)

No associations in acute case-control or
population-based studies
Other Potential Exposures to Blood - II

Biologically plausible but no data showing
these practices, procedures, or histories alone
place persons at increased risk for HCV

May be limited to certain settings and account
for small fraction of cases
– e.g., prisons, unregulated practitioners,
populations with certain cultural practices, etc.

Risk factor or high prevalence identified in
selected subgroup cannot be extrapolated to
the population
National Hepatitis C Prevention Strategy
• Prevent HCV infection
• Detect and control chronic liver disease
• Evaluate effectiveness of activities
• Conduct surveillance and research
Prevention Activities
Primary = Prevent HCV Transmission
• high risk activities - IDU, high risk sex
• nosocomial, occupational, transfusions and transplant
Secondary = Reduce Risk of Chronic Liver Disease
• identify, test, counsel, medical management
Reasons to Identify Persons with
Chronic HCV Infection
• Medical management
– evaluate for chronic liver disease
– treatment if indicated
– substance abuse treatment (alcohol, drugs) if
appropriate
– immunization (HB, HA, influenza, pneumo)
• Counsel to prevent disease transmission
– household contacts
– sexual contacts
– drug use contacts
HCV Testing Routinely Recommended
Based on increased risk for infection
• Ever injected illegal drugs
• Received clotting factors made before 1987
• Received blood/organs before July 1992
• Ever on chronic hemodialysis
• Evidence of liver disease
Recommendations for Prevention and Control of Hepatitis C Virus (HCV) Infection and HCVRelated Chronic Disease. MMWR 1998; 47: RR-19
HCV Testing Routinely Recommended
Based on need for exposure management
 Healthcare, emergency, public safety
workers after needle stick/mucosal
exposures to HCV-positive blood

Children born to HCV-positive women
Recommendations for Prevention and Control of Hepatitis C Virus (HCV) Infection and HCVRelated Chronic Disease. MMWR 1998; 47: RR-19
National Hepatitis C Prevention Strategy
Communication of Information on Hepatitis C
education of health care professionals
public service advertising
education of persons in groups at risk of
infection
–
–
transfusion recipients
injection drug users
Most difficult task: keeping messages factually correct
Geographic and Temporal Differences in the
Epidemiology of HCV Infection

HCV infection is endemic in most parts of
the world.

Substantial geographic and temporal
differences in endemicity of HCV infection
– related to frequency and extent to which
various risk factors contributed to transmission
Estimated Prevalence of Anti-HCV
WHO Global Burden of Disease Estimate, CDC, Unpublished data
Geographic Patterns of Age-Specific
Prevalence of HCV Infection
Percent Anti-HCV Positive
50
Egypt
40
30
20
Japan, Italy
10
U.S., Australia
0
0-9
10-19
20-29
30-39
Age Group (Years)
40-49
50+
Geographic Differences in
HCV Transmission Patterns
Exposures among
prevalent infections
Importance of Exposures by
HCV Endemicity
Low
Moderate
High
Injecting drug use
Transfusions
++++
+++
++
+++
+
+++
Health-care related
Unsafe injections
Folk medicine
+/+/-
++++
++++
++
++++
++++
No data
Children Playing with Medical Waste, Bangladesh
Relative Importance of Risk Factors for Hepatitis C
and Prevention Strategies by HCV Endemicity
High/Moderate Endemicity
Nosocomial
Transfusion
Low Endemicity
Injection Drug Use
Other
Safe blood supply
Infection control
Other
Sexual
Risk reduction counseling
and services
Adequate
resources
Identify persons at high risk
for counseling, testing, and medical management
Viral Hepatitis - Overview
A
B
C
D
E
Feces
Blood*
Blood*
Blood*
Feces
fecal-oral
Percutaneous
Percutanous
Percutaneous
fecaloral
Chronic
infection
no
yes
yes
yes
no
Vaccine
yes
yes
no
yes**
no
pre/post
(IG)
post
(HBIG)
no
no
no
Source of
virus
Route of
transmission
Pre/Post
prophylaxis
* Blood and blood-derived body fluids
**Prevention of Hep B with vaccine