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Viral Hepatitis

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 Viral Hepatitis – Historical Perspective

Enterically
“Infectious” A E transmitted

Viral “NANB”
hepatitis C
Parenterally
“Serum” B D transmitted
other

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 A, B, Cs of Viral Hepatitis imp

• A
– fecal-oral spread: hygiene, drug use, men having
sex with men, travelers, day care, food
– vaccine-preventable
• B
– sexually transmitted – 100x more infectious than
HIV
– blood-borne (sex, injection drug use, mother-
child, and health care)
– vaccine-preventable
• C
– blood borne (injection drug use primarily)
– 4-5 times more common than HIV
– NOT vaccine-preventable! 4
 Viral Hepatitis Overview

Types of Viral Hepatitis

A B C D E
Source of feces blood/ blood/ blood/ feces
virus blood-derived blood-derived blood-derived
body fluids body fluids body fluids

Route of fecal-oral percutaneous percutaneous percutaneous fecal-oral

transmission permucosal permucosal permucosal

Chronic no yes yes yes no

infection

Prevention pre- pre/post- blood donor pre/post- ensure safe

exposure exposure screening; exposure drinking
immunization immunization risk behavior immunization; water
modification risk behavior
modification
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 Acute Hepatitis – Clinical Symptoms
Asymptomatic > Symptomatic > Fulminant Liver
Failure > Death

Symptoms (if present) are the same, regardless of

cause (e.g., A, B, C, other viruses, toxins)
• Nausea, vomiting
• Abdominal pain
• Loss of appetite
• Fever
• Diarrhea
• Light (clay) colored stools
• Dark urine
• Jaundice (yellowing of eyes, skin) most imp point
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Infectious hepatitis, epidemic hepatitis,
epidemic jaundice.

• Likelihood of symptomatic illness directly related to age

• Children are usually asymptomatic, adults symptomatic
• Onset is usually abrupt with fever followed within few days
by jaundice.
• Complete recovery is the rule (no chronic sequelae).
• The case-fatality rate among persons of all ages is
approximately 0.3% compare b\w other types of Hb
• but is approximately 2% among persons > 40 years.
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It is worldwide
In developing countries, it occurs in
endemic and epidemic forms b\c it is related
to hygiene due to:

• Poor environmental sanitation

• Overcrowding
• Lack of personal hygiene.

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Geographic Distribution of HAV Infection

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 Global Patterns of
Hepatitis A Virus Transmission

Disease Peak Age Transmission

Endemicity Rate of Infection Patterns

High Low to high Early childhood Person to person;

outbreaks uncommon
Moderate High Late childhood/ Person to person;
young adults food and waterborne
outbreaks
Low Low Young adults Person to person;
food and waterborne
outbreaks
Very low Very low Adults Travelers; outbreaks
uncommon

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 Hepatitis A Virus
 Picornavirus (RNA)
 Stable at low pH
 Inactivated by high temperature, imp
formalin, chlorine

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• Human either he is carrier or he is
symptomatic
 clinical
 sub-clinical cases
 incubating carriers

Through anal orifice with faeces.

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 1. Fecal-oral route. Indirect route
2. Common vehicle; contaminated
water and food.
3. Direct contact occurs among male
homosexuals.
4. Rarely through blood transfusion
and contaminated syringes.
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 Through the
mouth.

• Susceptibility is general.
• Post infection immunity after the attack
probably lasts for life.

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• Incubation period 28 days (range 15-50
days)
• 4 weeks

• Last two weeks of incubation period

• maximum infectivity is during the latter

half of the incubation period (2 weeks
before and 1 week after onset of
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jaundice).
 Prevention of Hepatitis A

 Vaccination most imp

 Immune globulin
 Good hygiene (hand washing)
 Clean water systems; avoidance of food
contamination
 Food sanitation especially shell fish and
raw eaten food.

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 Hepatitis A Prevention – Immune Globulin
 Pre-exposure
– travelers to intermediate and high
HAV-endemic regions

 Post-exposure (within 14 days)

Routine
– household and other intimate contacts
Selected situations
– institutions (e.g., day care centers)
– common source exposure (e.g.,
food prepared by infected food handler)
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 Hepatitis A Vaccine
 Inactivated whole virus vaccine.
 Pediatric and adult formulations in 1996
 Licensed for persons 1 year of age and older.
 Schedule 2 doses imp to know
 First dose then booster dose 6-18 months after first.
 Gives protection after 4 weeks of the fist dose.
 The vaccine should be administered intramuscularly.
 Site: deltoid muscle.
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 Indications of Hepatitis A Vaccine
 Persons at increased risk for infection
– travelers to intermediate and high HAV-endemic
countries
(Individuals who will travel to high‑risk areas <4 weeks
after the initial dose of vaccine should also be given IG)
– MSM (Men who have sex with men)
– illegal drug users
– Persons who have clotting factor disorders
– persons with chronic liver disease

 Communities with historically high rates of hepatitis A

-routine childhood vaccination
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 Serum hepatitis, serum
jaundice.

 Clinical signs & symptoms occur more in adults.

 At least 50% of infections are asymptomatic

 Onset is usually gradual with anorexia, nausea and

vomiting, often progressing to jaundice.

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 Hepatitis B – Clinical Features

• Incubation period: Average 60-90 days

Range 45-180 days
• Clinical illness <5 yrs, <10%
(jaundice): >5 yrs, 30%-50%

• Acute case-fatality rate: 0.5%-1%

• Chronic infection: imp <5 yrs, 30%-90%

>5 yrs, 2%-10%

• Premature mortality from

chronic liver disease: 15%-25%
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Symptomatic Infection of Hepatitis B Virus by Age at Infection

100
Symptomatic Infection

80

60

40

20
(%)

Symptomatic Infection
0

Older Children
7-12 mos
1-6 mos

1-4 yrs
Birth

and Adults
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Risk of Chronic HBV Carriage by Age of
Infection

100
90
80
70
Carrier risk (%)

60
50
40
30
20
10
0
Birth 1-6 m o 7-12 m o 1-4 yrs 5+ yrs
Ag e o f in fectio n

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 Outcome of Hepatitis B Virus Infection
by Age at Infection
100 100

Symptomatic Infection (%)

Chronic Infection (%)

80 80

60 60
Chronic Infection

40 40

20 20
Symptomatic Infection
0 0

Older Children
7-12 mos
1-6 mos

1-4 yrs
Birth

and Adults
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 Outcome of HBV Infection

Gow, P. J et al. BMJ 2001;323:1164-1167

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Chronic Hepatitis B Virus Infection imp

•Overall risk: 10% of all acute infections.

•About 15%-25% of persons with chronic HBV
infection might die from either cirrhosis or liver cancer
•Chronic infection occurs in:
~ 90% of infants infected with HBV at birth
~ 30% of children infected at age 1- 5 years
2- 6% of people infected after age 5 years
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 Geographic Distribution of Chronic HBV Infection
‫لزم نعرف الدول اللي منتشر فيها خاصه السعوديه‬

HBsAg Prevalence

≥ 8% - High
2-7% - Intermediate
<2% - Low

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 Global Patterns of
Chronic HBV Infection
 High (>8%):
– 45% of global population
– early childhood infections common

 Intermediate (2%-7%):
– 43% of global population
– infections occur in all age groups

 Low (<2%):
– 12% of global population
– most infections occur in adult risk groups
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 Hepatitis B Virus

HBsAg Double-Stranded
DNA
HBsAg

HBcAg

HBeAg
 The presence of HBsAg indicates active infection or chronic
carrier. 30

 Antibody to HBsAg, from either disease or vaccine, indicates

 Human (cases and carriers).

 Human blood and blood products can transmit

infection if not screened for HBs Ag.

 Other body Fluids have the virus with varying

concentrations.

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 Concentration of HBV
in Various Body Fluids

Low/Not
High Moderate Detectable

blood semen urine

serum vaginal fluid feces
wound exudates saliva sweat
tears
breast milk

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1.Parenteral: Unsafe injections and transfusions,
organ transplants, sharing needles,
haemodialysis, needle sticks, tattooing , razors
and toothbrushes. Most imp
2.Perinatal exposure, especially when HBs Ag
carrier mothers are also HBe Ag positive.

3.Sexual exposure.
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 From 45-180 days, average 60-90 days. ‫ شهور‬6‫توصل ل‬

• 1-2 months before the onset of symptoms

• during acute clinical course
• during the chronic carrier state which may persist
for life.

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 Elimination of HBV Transmission

Strategy imp
 Prevent perinatal HBV transmission
 Routine vaccination of all infants
 Vaccination of children in high-risk
groups
 Vaccination of adolescents & all
children up through age 18
 Vaccination of adults in high-risk
groups

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 Hepatitis B Vaccine
• Licensed in 1982
• Currently, subunit recombinant HBs Ag
• given IM in the deltoid region.

• 3 dose series, typical schedule 0, 1-2, 4-6 months - no

maximum time between doses (no need to repeat missed
doses or restart)

• Protection
• ~30-50% dose 1
• 75% - dose 2
• 96% - dose 3
• lower protection in older, immunosuppressive
illnesses (e.g., HIV, chronic liver diseases, diabetes),
obese, smokers 36
Indication of Hepatitis B Vaccination
 Routine infant
 Ages 11-15 “catch up”, and through age 18 years
 Over 18 – high risk
– Occupational risk health care workers (HCWs)
– Hemodyalisis patients
– All clinic clients of sexually transmitted diseases (STD)
– Multiple sex partners or prior STD
– MSM (Men having sex with men)
– IDU (injecting drug users)
– Institution for developmental disability (Staff & clients)

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Prevention of perinatal HBV transmission

Prevent perinatal HBV transmission by:imp

• screening all pregnant women for hepatitis
B surface antigen (HBsAg) &
• providing hepatitis B immune globulin
(HBIG) & and
• hepatitis B vaccine to infants of
HBsAg‑positive mothers

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 Immunoglobulins (HBIG):
(HBIG) is indicated in combination with the
vaccine in:
accidental needle stick injury
sure sexual exposure
perinatal exposure
In blood banks:
screening of blood donors
And avoid donors from risky group.
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 Use of adequately sterilized syringes and needles or

preferably use disposal equipment.

 Discourage risky behaviors e.g. tattooing, drug abuse

and extramarital relations.

 Avoid transmission from persons with e antigen,

especially medical and dental personnel who routinely
perform invasive procedures.

 Health care personnel should follow the universal

precautions.
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 Hepatitis D (Delta) Virus

δ antigen HBsAg

RNA
HDV is a defective single‑stranded RNA virus (delta Ag)
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It requires HBV for synthesis of envelope protein composed of HBsAg.
 Geographic Distribution of HDV Infection

Taiwan

Pacific Islands

HDV Prevalence
High
Intermediate
Low
Very Low 44

No Data
 Hepatitis D - Clinical Features

• Coinfection with HBV imp

– severe acute disease
– low risk of chronic infection

• Superinfection on top of chronic HBV

– usually develop chronic HDV infection
– high risk of severe chronic liver disease

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 Hepatitis D Virus
Modes of Transmission

• Percutanous exposures
injecting drug use

• Permucosal exposures
sex contact

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 Hepatitis D - Prevention

• HBV-HDV Coinfection
– Pre or postexposure prophylaxis to prevent HBV
infection (HBIG and/or Hepatitis B vaccine)

• HBV-HDV Superinfection
– Education to reduce risk behaviors among persons
with chronic HBV infection

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Prevalence of HCV Infection Among Blood Donors

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 Hepatitis C – Clinical Features

Incubation period: Average 6 - 7 wks
Range 2 – 26 wks
 Acute illness (jaundice) Mild (≤20%)
 Case fatality rate Low
 Chronic infection 60%-85%
 Chronic hepatitis 70%

Cirrhosis 5%-20%
 Mortality from CLD : 3%

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 Chronic Hepatitis C Factors Promoting
Progression or Severity imp
• Increased alcohol intake

• Age > 40 years at time of infection

• HIV co-infection

• Other
• Male gender
• Chronic HBV co-infection

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Natural History of HCV Infection
100 People Time
15%
85%
Resolve (15)
Chronic (85)
80%
20%
Stable (68)
Cirrhosis (17)
75%

Stable (13) 25%

Mortality (4)

Leading Indication for Liver Transplant

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 Risk Factors Associated with
Transmission of HCV
• Illegal injection drug use most common
• Transfusion or transplant from infected donor
• Occupational exposure to blood
– Mostly needle sticks
• Iatrogenic (unsafe injections)
• Birth to HCV-infected mother
• Sexual/household exposure to anti-HCV positive
contact
• Multiple sex partners
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 Sources of Infection for
Persons With Hepatitis C

Injecting drug use 60% Sexual 15%

Transfusion 10%
(before screening)

Occupational 4%

Other 1%*

Unknown 10%

* Nosocomial; iatrogenic; perinatal

Source: Sentinel Counties, CDC

Source: Centers for Disease Control and Prevention
 Other modes of transmission:
 percutaneous procedures using inadequately
sterilized equipment (e.g. ear and body piercing,
circumcision, tattooing)
 HCV do not spread by sneezing, hugging,
coughing, food or water, sharing eating utensils, or
casual contact

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 Prevention of HCV transmission

- Reduce or Eliminate Risks for Acquiring HCV Infection

- Preventing HCV Transmission from patients to Others

- HCV Testing

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Reduce or Eliminate Risks for Acquiring HCV
Infection
 Screening and testing donors of blood, organs,
and tissues
 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
 Infection control practices
 Blood and body fluid precautions

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Preventing HCV Transmission from patients to Others

(Avoid Direct Exposure to Blood imp)

 Anti-HCV positive individuals should 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

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HCV Testing Routinely Recommended
(Based on Risk for Infection)
 Persons who ever injected illegal drugs

 Persons with selected medical conditions

– received clotting factor concentrates produced
before 1987
– ever on chronic hemodialysis
– evidence of liver disease

 Prior recipients of transfusion/organs

– before July 1992
– notified that donor later tested positive

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HCV Testing Routinely Recommended
(Based on Recognized Exposure)
 Healthcare, emergency medical, and public
safety workers after needle sticks, sharps, or
mucosal exposures to HCV- positive blood

 Children born to HCV-positive women

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Routine HCV Testing Not Recommended
(Unless Risk Factor Identified)

 Health-care, emergency medical, and

public safety workers
 Pregnant women
 Household (non-sexual) contacts of HCV-
positive persons
 General population

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 Public Health Service Guidelines for
Anti-HCV-Positive Persons

Anti-HCV-positive persons should:

• Be considered potentially infectious
• Keep cuts and skin lesions covered
• Be informed of the potential for sexual transmission
• Be informed of the potential for perinatal
transmission
– no evidence to advise against pregnancy or
breastfeeding
Anti-HCV-positive persons should not:
• Donate blood, organs, tissue, or semen
• Share household articles (e.g., toothbrushes,
razors) 62
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Geographic Distribution of Hepatitis E

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 Hepatitis E – Epidemiologic Features

• Most outbreaks associated with fecally

contaminated drinking water imp

• Minimal person-to-person transmission

• U.S. cases usually have history of travel to

HEV-endemic areas

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 Hepatitis E – Clinical Features

Incubation period: Average 40 days

Range 15-60 days
Case-fatality rate: Overall, 1%-3%
Pregnant women,
15%-25%
Illness severity: Increased with
age
Chronic sequelae: None identified

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 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 trails. 67
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