1

DEPARTMENT OF PUBLIC
HEALTH DENTISTRY
SEMINAR
HEPATITIS B

Presented by:Dr. Amrita Rastogi

CONTENTS
HISTORY
INTRODUCTION
PREVALENCE OF HEPATITIS B
HEPATITIS B VIRUS
STRUCTURE OF HEPATITIS B VIRUS
REPLICATION OF HEPATITIS B VIRUS
MODES OF TRANSMISSION
HIGH-RISK GROUPS FOR HBV INFECTION
STAGES OF THE DISEASE

PATHOLOGY & PATHOGENISIS

SIGNS AND SYMPTOMPS
CLINICAL FEATURES
CLINICAL OUTCOME OF THE DISEASE
DIAGNOSIS
LEVELS OF PREVENTION
CONCLUSION
REFERENCES

HISTORY (1)
o

Its an ancient disease first described in 5 th century B.C.

Earliest recognized blood-borne outbreak of hepatitis

was in Germany in 1883 after receiving smallpox
vaccine.

In 1947 MacCalum and Bauer introduce the term

Hepatitis A for infectious and Hepatitis B for serum
hepatitis
5

This terminology was adopted by WHO in 1973

INTRODUCTION (1)(2)

The term hepatitis describes inflammation of the liver.

Hepatitis may be caused by alcohols, drugs, autoimmune
diseases, metabolic diseases, and viruses. Viral infections
accounts for more than half the cases of acute hepatitis.

Viral hepatitis is a systemic infection affecting the liver

predominately with primary inflammation of the liver by
any one of a heterogeneous group of hepatotropic viruses

Different types of Hepatitis viruses are:

Hepatitis A (HAV) (1973)

Hepatitis B (HBV) (1970)

Hepatitis C (HCV) (1988)

Hepatitis D (HDV) (1977)

Hepatitis E (HEV) (1983)

Hepatitis F Not separate entity Mutant of B Virus.

Hepatitis G (HGV) (1995)

7

All of these are RNA viruses except HBV which is a

DNA viruses.

The viral hepatitis is classified as:

Acute hepatitis (self-limited liver injury of less than
6 months)

Chronic hepatitis ( hepatic inflammation more than 6

months)
8

Hepatitis B is a serious and common infectious diseases

of the liver, affecting millions of people throughout the
world.

The severe pathological consequences of persistent HBV

infections include the development of chronic hepatic
insufficiency, cirrhosis and hepato cellular carcinoma
(HCC). In addition, HBV carriers can transmit the
disease for many years.
9

PREVALENCE OF HEPATITIS B (4)(5)

More than 2,000 million people alive today have been

infected with HBV at some time in their lives. Of these,
about 350 million remain infected chronically and become
carriers of virtues. Three quarters of the worlds population
live where there are high levels of infection.

Every year there are over 4 million acute causes of HBV, and
about 25% of carriers, 1 million people a year, die from
chronic active hepatitis, cirrhosis or primary liver cancer.

10

. Worldwide prevalence of hepatitis B carriers and primary hepatocellular

carcinoma. (Courtesy Centers for Disease Control and Prevention, Atlanta.)

11

The world can be divided into 3 areas where the

prevalence of chronic hepatitis infection is high (>8%),
intermediate(2-8%), and low (<2%).

High endemicity areas include south-east Asia and

Pacific Basin, sub-Saharan Africa, parts of middle east,
some countries in eastern Europe. In these areas about
70-90% of population becomes HBV infected before the
age of 40, and 8 to 20% of people are HBV carriers.
12

Low endemicity areas include North America, Western

and Northern Europe, Australia. The carrier rate here
2% and less than 20% of the population infected with
HBV

The rest of the world falls into intermediate range of

HBV prevalence, with 2 to 8% of a given population
being HBV carriers.
13

HEPATITIS B VIRUS (5)(6)

Hepatitis B is caused by the hepatitis B virus (HBV), an

enveloped virus containing a partially double stranded,
circular DNA genome, and classified within the family
of hepadnavirus.

14

The virus interferes with the functions of liver while

replicating in hepatocytes. The immune system is then
activated to produce a specific reaction to combat and
possibly

eradicate

the

infectious

agents.

As

consequence of pathological damage, the liver becomes

inflamed.

HBV may be the cause of upto 80% of all cases of

hepatocellular carcinoma world wide.

15

STRUCTURE OF HEPATITIS B VIRUS (5)(6)(7)

Hepatitis virus is a DNA virus with a remarkably

compact genomic structure.

It have circular partially double-stranded DNA viruses.

Replication occurs by reverse transcriptase.

It is small, circular, 3200 base- pair size, HBV DNA

codes for four sets of viral products and has a complex,
multi particle structure.
16

The hepatitis B virus is 42nm in diameter and composed

of 27 nm nucleocapsid core (HBcAG), surrounded by
outer lipo protein coat (also called envelope) containing
the surface antigen (HBsAG)

Virion also referred to as Dane particle (ds-tranded

DNA)
Core antigens located in the center (nucleocapsid)
* Core antigen (HBcAg)
* e antigen (HBeAg
17

18

HBsAg = surface (coat) protein

HBcAg = inner core protein
HBeAg = secreted protein

19

REPLICATION OF HEPATITIS B VIRUS (7)(8)

The HBV virion binds to a receptor at the surface of the

hepatocyte.

Viral nucleocaspids enter the cell and reach the nucleus,

where the viral genome is delivered.

20

Reverse transcription: one of the mRNAs is replicated with a

reverse transcriptase making the DNA that will eventually be
the core of the progeny virion

RNA intermediate: HBV replicates through an RNA

intermediate and produces and release antigenic decoy
particles.

Integration: Some DNA integrates into host genome causing

carrier state
21

HOW THE VIRUS REPRODUCES ?

1.First the virus attached to a liver cell membrane

22

2. The virus is then transported into the liver cell.

23

3. The core particle then releases its contents of DNA and

DNA polymerase into the liver cell nucleus.

24

4.Once within the cell nucleus

the hepatitis B DNA causes
the liver cell to produce, via
messenger

RNA

HBs

protein , HBc protein , DNA

polymerase, the HBe protein
,

and

other

undetected

protein and enzymes.

5. DNA polymerase causes the
liver cell to make copies of
hepatitis

DNA

messenger RNA.

from
25

6. The cell then assembles live copies of virus.

26

7.However because of the excess numbers of surface

proteins produced many of these stick together to form
small spheres and chains. These can give a characteristic
ground glass appearance to blood samples seen under
microscope.

27

8. The copies of the virus and excess surface antigen are

released from the liver cell membrane into blood stream
and from there can infect other liver cells

28

29

MODES OF TRANSMISSION (9)

Sexual - sex workers and homosexuals are particular at

risk.

Parenteral - IVDA, Health Workers are at increased risk.

Perinatal - Mothers who are HBeAg positive are much

more likely to transmit to their offspring than those who
are not. Perinatal transmission is the main means of
transmission in high prevalence populations.

30

Perinatal transmission

Horizontal transmission

Perinatal
90% of

infected
infants
become
chronically
infected

Mother
Host

Infant

6% of

people
infected over
the age of 5
become
chronically
infected

Recipient
Child-to-child
Contaminated needles
Sexual contacts
Healthcare worker
Blood transfusion

31

Heterosexual*
(41%)

Injecting
Drug Use
(15%)

Homosexual Activity (9%)

Household Contact (2%)

Health Care Employment (1%)
Others (1%)
Unknown (31%)

32

HIGH-RISK GROUPS FOR HBV

INFECTION (9)

People from endemic regions

Babies of mothers with chronic HBV

Intravenous drug abusers

People with multiple sex partners

Hemo dialysis patients

Health care personnel who have contact with blood

Residents and staff members of institutions for the

mentally retarded

33

STAGES OF THE DISEASES (10)(11)

FIRST STAGE

The duration of this stage for healthy adults is

approximately 2-4 weeks and coincide with the
incubation period. For newborns, the duration of this
period often is decades.

Active viral replication is known to continue despite

little or no elevation in the aminotransferase levels and
no symptoms of illness.

34

SECOND STAGE

In the second stage, an inflammatory reaction with a

cytopathic effect occurs.

HBeAg can be identified in the sera and a decline of the

levels of HBV DNA is seen.

The duration of this stage for patients with acute infection is

approximately 3-4 weeks (symptomatic period).

For patients with chronic infection, 10 years or more may

35

elapse before cirrhosis develops .

THIRD STAGE

In the third stage, the host can target the infected

hepatocytes and the HBV Viral replication no longer occurs.

HBeAb can be detected. The HBV DNA levels are lower or

undetectable, and aminotransferase levels are within the
reference range.

In this stage, an integration of the viral genome into the

host's hepatocyte genome takes place.

HBsAg still is present.

36

FOURTH STAGE
In the fourth stage, the virus cannot be detected and
antibodies to various viral antigens have been produced.

Different factors have been postulated to influence the

evolution

of

these

stages,

including

age,

sex,

immunosuppression, and co-infection with other viruses.

37

PATHOLOGY (11)(12)

Three antigen-antibody system

1) HBsAg-- anti-HBs system:

HBsAg appears 1-2 weeks (late up to 11-12 weeks) after

exposure, persists for 1-6 weeks( even 5 months) in acute

hepatitis B.

In chronic patients or carrier, HBsAg persist many years

HBsAg is the marker of infectivity

38

 HBsAg can be found in blood and secretions: saliva,

urine, semen, tears, sweat and breast milk

Anti-HBs appear after HBsAg disappear several weeks

(or months) anti-HBs is protective antibody, can persist

for many years

39

2) HBcAganti-HBc system

HBcAg can be found in the nuclei of liver cells, no free

HBcAg in serum

HBcAg is the marker of replication of HBV

The stage called window phase

Anti-HBc IgM is a marker of acute infection and acute attack

of chronic infection of HBV. Anti-HBc IgG is the marker of
past infection, high titer means low level replication of HBV
40

3) HBeAganti-HBe system

HBeAg is a soluable antigen

HBeAg is a reliable indicator of active replication of HBV

Anti-HBe is a marker of reduced infectivity. If exist long

may be a marker of integration of HBV into liver cell

41

42

43

PATHOGENISIS (11)
HBV

invades into the human body by skin and mucosa,

Via blood flow enters the liver and other organs such as
pancreas, bile ducts, vessels, WBC, bone marrow,
glomerular basement membrane.
HBcAg,HBsAg,HBeAg

and HLA-appear on the liver

cells infected with are recognized by CTL simultaneously

and lead to the cytolysis of liver cells.

44

 Helper T cell are activated by the receptor of HLA-

on its surface combing with HBsAg, HBcAg and

HLA- antigen on the B cells promote B cell to release
anti-HBs and clear HBV
The representation of HBcAg on the liver cells may

cause cytopathy

45

SIGNS AND SYMPTOMS (12)

Fever
Fatigue
Loss of appetite
Nausea
Vomiting
Abdominal pain
Dark urine
Clay-colored bowel movements
Joint pain
Jaundice
Hepatomegaly

46

Symptoms begin an average of 3 months (range: 2

5months) after exposure to HBV.

Symptoms typically last for several weeks but can persist

for up to 6 months.

47

CLINICAL FEATURES (12)(13)

Incubation period

Average 60-90 days

Range 45-180 days

Clinical illness (jaundice)

<5 yrs- <10%

>5yrs- 30-50%

Acute case-fatality rate

0.5%-1%

Chronic infection

<5 yrs- 30-90%

>5yrs- 2-10%

Premature mortality from

chronic liver disease

15%-25%
48

CLINICAL FEATURES

ACUTE HEPATITIS B

Incubation period- 45to 120 days average 60 to 90 days.

Phases of disease
1.

Preicteric

2.

Icteric

3.

Convalescent

49

Preicteric

a.

Tiredness

b.

Anorexia

c.

Vague abdominal discomfort

d.

Nausea & Vomiting

e.

Sometime arthralgias & rash

50

Icteric

a.

Within 10days of initial symptoms

b.

Dark urine Pale stool

Yellowish discoloration of

mucous membranes.
c.

Total bilirubin- exceeds 20 to 40 mg/l

d.

Hepatosplenomegaly

e.

After disappearance of jundice-Anti HBs.

51

Convalescent

a.

Anti HBc IgM to IgG type

b.

Transient presence of HBsAg, HBeAg and viral DNA

(<6 months)

c.

Seroconversion to anti HBsAg and anti HBeAg

52

Chronic Hepatitis B

After acute infection virus remain in 5 to 10% cases of

adult, even more higher among children upto 70 to 90%.

350 million of person worldwide are chronic carriers.

Among them 100 million in China.

Among the persistent carrier 70% will develop Chronic

persistent hepatitis and remaining 30% will develop
Chronic active hepatitis.

53

CLINICAL OUTCOMES OF
HEPATITIS B INFECTIONS (14)(15)

54

HEPATOCELLULAR CARCINOMA

Only 5% patient with cirrhosis develop HCC.

HCC is responsible for 90% of primary malignant tumor of

liver.

Worldwide 7th most common cancer in male while 9th in

female.

Causes >500000 deaths annually with male & female ratio

4:1.
55

Appears after a mean duration of about 35 years of HBV

infection.

56

FULMINANT HEPATITIS

Rare condition, develop in about 1% cases.

It is due to massive necrosis of liver substance.

Usually fatal

Survival in adult is uncommon.

Genetic heterogeneity, co-infection, host immunological

factors are responsible.
57

EXTRA-HEPATIC MANIFESTATIONS (15)

Mediated by circulating immune complexes

Both acute hepatitis & chronic hepatitis
Acute hepatitis 10-20%
Serum sickness like illness,
Fever, rash, artralgia.
Gainotti- Crosti syndrome
Papular acrodermatits (children)
Glomerular disease

58

DIAGNOSIS (16)(17)

HBsAg - used as a general marker of infection.

HBsAb - used to document recovery and/or immunity to

HBV infection.

anti-HBc IgM - marker of acute infection.

anti-HBcIgG - past or chronic infection.

HBeAg - indicates active replication of virus and

therefore infectiveness.

59

Anti-Hbe - virus no longer replicating. However, the

patient can still be positive for HBsAg which is made by
integrated HBV.

HBV-DNA - indicates active replication of virus, more

accurate than HBeAg especially in cases of escape
mutants. Used mainly for monitoring response to
therapy.

60

CONCENTRATION OF HEPATITIS B VIRUS IN

VARIOUS BODY FLUIDS (16)

High

Moderate

Low/Not
Detectable

blood
serum
wound exudates

Semen
Vaginal fluid
Saliva

Urine
Feces
Sweat
Tears
Breast Milk
61

LEVELS OF PREVENTION FOR HEPATITIS B (17)(18)

Primary Prevention

Advocacy and raising awareness of all types of viral

hepatitis infections help to reduce transmission in the
community.
Safe and effective vaccines are widely available for the
prevention of HAV and HBV infections and an HEV
vaccine has recently been licensed in China.
Implementation of blood safety strategies, including
blood supplies based on voluntary non-remunerated
blood donations, effective public education on blood
donation, donor selection, and quality-assured screening
of all donated blood and blood components used for
transfusion can prevent transmission of HBV and HCV.

62

Infection control precautions in health care and community

settings can prevent transmission of viral hepatitis as well as
many other diseases.
Safe injection practices can protect against HBV and HCV
transmission.
Safer sex practices.
Harm reduction practices for injecting drug users prevent
HAV, HBV and HCV transmission.
Occupational safety measures prevent transmission of viral
hepatitis to health care workers.
Safe food and water provide protection against HAV and HEV
infection

63

HEPATITIS B VACCINATION (19)

1965

Discovery of Australian antigen

1973

Successful HBV infection of chimpanzees

1981

Licensure of plasma-derived vaccine

1986

Licensure of recombinant vaccine

1991

Universal infant vaccination

1996

Universal adolescent vaccination

64

Vaccines against hepatitis B were introduced in the early,

1980s.
More than 110 countries have adopted a national policy
of immunizing all infants with hepatitis B vaccine.
HB vaccine is the most effective tool in preventing the
transmission of HBV and HVD. Vaccine are composed
of the surface antigen of HBV(HBsAg), and are
produced by two different methods: plasma derived or
recombinant DNA.

65

PLASMA DERIVED VACCINE

These vaccines, derived from the plasma of HBsAgpositive donors, consist of highly purified, formalininactivated and/or heat-inactivated, alum-absorbed,
hepatitis B sub virion particles (22nm) of HBsAg that are
free to detectable nucleic acid and therefore,
noninfectious.
The first plasma derived vaccines were manufactured in
USA and France in 1981-1982.

66

RECOMMENDATION FOR PRE

EXPOSURE IMMUNIZATION WITH
HEPATITIS B

Infants (Universal immunization)

Infants and adolescents not vaccinated previously
(catch-up vaccination)
Person with occupational risk
Haemodialysis patients
Recipients of blood and blood products
Susceptible drug abusers.
Sexually active men or women
Susceptible inmates who have a history of high risk
behavior
67

Household contacts and sex partners of HBV carriers

Population with a high incidence of disease
International traveler to area of high HBV endemicity
Transplant candidates.

68

COMBINATION VACCINES
The HBsAg vaccines can be combined with other
vaccines such as Calmetta-Guerin Bacillus(BCG),
measles, mumps, and rubella, Haemophilus influenzae b,
diptheria, tetanus and petussis combined with polio.
Neonates born to mother who are HBsAg positive should
be given a combination of passive and active
immunization to provide immediate protection in the
first 6 hours after delivery, followed by long term
immunity with the vaccine.

69

The vaccine is administered by intramuscular injection

in the antrolateral aspect of the thigh of the new born and
infants or deltoid (arm) muscle of children and adults in
order to achieve optimal protection.
It is particular effective within 48 hours of the incident.
It may also be given to neonates who are at increased
risk of contracting hepatitis B i.e. whose mothers are
HBsAg and HBeAg positive.
Hepatitis B Immunoglobulin - HBIG may be used to
protect persons who are exposed to hepatitis B.

70

HEPATITIS B VACCINE
ADOLESCENT AND ADULT SCHEDULE

Dose
Primary 1
Primary 2
Primary 3

Usual
Interval
--1 month
5 months

Minimum
Interval
--4 weeks
8 weeks*

*third dose must be separated from

first dose by at least 16 weeks
71

RECOMMENDED DOSE OF HEPATITIS B VACCINE

Infants and children

<11 years of age
Adolescents 11-19 years

Recombivax HB
Dose (mcg)
0.5 mL (5)

Engerix-B
Dose (mcg)
0.5 mL (10)

0.5 mL (5)

0.5 mL (10)

1.0 mL (10)

1.0 mL (20)

Adults >20 years

72

Factors for decreased vaccine response:

- Smoking
- Obesity
- HIV infection
- Imunocompromised patients
-Haemodialysis
- Prematurity
- Genetic factors
- Chronic disease.
- Subcutaneous injection
- Freezing of vaccine
- Accelerated schedule

73

DENTAL CONSIDERATION
For

dentists : Hepatitis B & Hepatitis C virus are

important as they can be transmitted by various methods

as it is most common blood borne infection.
Its is associated with many clinical features which are
encountered by dentist like:
o Sjorgrens syndrome
o lichen planus
o glossitis and/or angular cheilosis
o Mucosal Ecchymosis
74

Management for dentists:

Pre Exposure vaccination : Engerix. Which is available

commonly.
Maintaining proper sterilization and infection control
measures.
More use of disposable products like disposable gloves,
mouth mask, syringes, etc.
Proper disposal of used needles.

75

ROLE OF A PUBLIC HEALTH DENTIST

A public health dentist can play an important role in preventing the
hepatitis B by:

Educating people about ways of mode of transmission of diseases.

By telling the real facts and myths related to disease.

To encourage people for vaccination

Telling about healthy lifestyle and habits to prevent any kind of

liver related diseases.
76

SECONDARY PREVENTION (20)

Early diagnosis provides the best opportunity for effective
medical support and prevention of further spread. It also
allows the infected persons to take steps to prevent
transmission of the disease to others. Early diagnosis of
those with chronic infection also allows people to take
precautions to protect the liver from additional harm,
specifically by abstaining from alcohol and tobacco
consumption and avoiding certain drugs that are known
to be toxic to the liver.

77

Treatment of acute HBV infection is primarily supportive.

Good nutrition and bed rest should be reinforced.

Abstinence from alcohol and the use of hepatotoxic drugs is

also necessary.

Conversely, chronic HBV infection may be progressive and,

therefore, requires management. The goals of therapy include
minimization of hepatocellular damage and viral clearance.

78

Possible adverse effects to interferon include fever and

chills, headache, depression, malaise, tachycardia, bone
marrow suppression, alopecia and, on rare occasion
,cardiac or renal failure.

79

In acute hepatitis B the treatment is basically

symptomatic
Rest
Ant emetics to control vomiting
Plenty of fluids and carbohydrates
Hepatotropic agents

80

 Chronic

Hepatitis B (20)(21)

Interferon - for HBeAg +ve carriers with chronic active hepatitis.

Response rate is 30 to 40%.

Lamivudine - a nucleoside analogue reverse transcriptase

inhibitor. Well tolerated, most patients will respond favorably.
However, tendency to relapse on cessation of treatment. Another
problem is the rapid emergence of drug resistance.

Successful response to treatment will result in the disappearance

of HBsAg, HBV-DNA, and seroconversion to HBeAg.

81

82

TERTIARY PREVENTION
There is no surgical treatment for hepatitis B.
In case of advanced liver damage because of hepatitis and
condition becomes life-threatening, their is need a liver
transplant.
In rare cases, acute hepatitis B progresses rapidly to liver
failure, a deadly condition called fulminant hepatitis. For
people who develop this condition, a liver transplant is the
only treatment choice.

83

CONCLUSION
Hepatitis B is the most common serious liver infection in
the world. It is caused by the hepatitis B virus (HBV)
that attacks liver cells and can lead to liver failure,
cirrhosis scarring) or cancer of the liver. The virus is
transmitted through contact with blood and bodily fluids
that contain blood.
84

The hepatitis B virus is 100 times more infectious than the

AIDS virus. Yet, hepatitis B can be prevented with a safe
and effective vaccine.

For the 400 million people

worldwide who are chronically

infected with hepatitis

B the vaccine is of no use. However, there are promising

new treatments for those who live with chronic
hepatitisB.
85

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Control
2. Fauci ,Braunwald, Isselbacher Harrisons Principle of internal
mediciene vol-2 14th edition.
3. Haslett, Chivers, Boon Davidsons Principles and Practice of
Mediciene. 2004 19th edition.
4. Churchills Illustrated Medical Dictionary, New York ,
Churchill Livingstone, 1989.
5. Harmanjit Singh Hira Text book of General Medicine for
Dental Students.
6. Manual of Clinical Microbiology, Patrick R Murray 9 th edition.
7. Topely and Wilsons, Virology volume-1 ,9th edition.

86

8. Mandells, Principle and Practice of Infectious Diseases,

5th edition
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Department of Communicable Diseases Surveillance
and Response
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Paniker,7th edition
11. European Association for the Study of the Liver. EASL
clinical practice guidelines: management of chronic
hepatitis B. J Hepatol 2009;50:227242.

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12. Ganem D, Schneider RJ. Hepadnaviridae: The Viruses and Their

Replication. In : Knipe DM et al., eds. Fields Virology, 4 th edition,
Philadelphia, Lippincott Willams& Wikins, 2001:2923-2969.
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Communicable
Diseases
Surveillance
and
Response;
WHO/CDC/LYO/2002.2: Hepatitis B.
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16. Gitlin N. Hepatitis B: diagnosis, prevention, and treatment.
Clinical Chemistry, 1997, 43:1500-1506.
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action;WHO/HSP/PED/HIP/GHP/2012.1

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18. Jacobsen KH, Wiersma ST. Hepatitis A virus

seroprevalence by age and world region, 1990 and
2005 Vaccine, 2010, 28: 66536657.
19. Perz JF et al. The contributions of hepatitis B virus and
hepatitis C virus infections to cirrhosis and primary
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20. World Health Organization. Hepatitis B vaccines.
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THANK YOU
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