1

DEPARTMENT OF PUBLIC

HEALTH DENTISTRY

SEMINAR

HEPATITIS B

Presented by:-

Dr. Amrita Rastogi

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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

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PATHOLOGY & PATHOGENISIS

SIGNS AND SYMPTOMPS

CLINICAL FEATURES

CLINICAL OUTCOME OF THE DISEASE

DIAGNOSIS

LEVELS OF PREVENTION

CONCLUSION

REFERENCES

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HISTORY (1)

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

o Earliest recognized blood-borne outbreak of hepatitis

was in Germany in 1883 after receiving smallpox

vaccine.

o In 1947 MacCalum and Bauer introduce the term

Hepatitis A for infectious and Hepatitis B for serum

hepatitis

o This terminology was adopted by WHO in 1973

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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 viruses6

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)

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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.

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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 world’s 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

11. Worldwide prevalence of hepatitis B carriers and primary hepatocellular

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

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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.

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.

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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.

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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 a

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

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18

HBsAg = surface (coat) protein

HBcAg = inner core protein

HBeAg = secreted protein19

REPLICATION OF HEPATITIS B VIRUS (7)(8)

20

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.

21

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

HOW THE VIRUS REPRODUCES ?

1.First the virus attached to a liver cell membrane

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

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3. The core particle then releases it’s contents of DNA and

DNA polymerase into the liver cell nucleus.

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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 B DNA from

messenger RNA.25

6. The cell then assembles “live” copies of virus.

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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.

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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

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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

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Perinatal transmission Horizontal transmission

Mother

Infant

Host

Perinatal

• 90% of infected infants become chronically infected

• 6% of people infected over the age of 5 become chronically infected

Recipient

Child-to-child

Contaminated needles

Sexual contacts

Healthcare worker

Blood transfusion

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Heterosexual*

(41%)

Homosexual Activity (9%)

Household Contact (2%)Health Care Employment (1%)

Others (1%)

Unknown (31%)

Injecting

Drug Use

(15%)

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.

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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

elapse before cirrhosis develops. 35

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.

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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

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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

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2) HBcAg—anti-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 HBV40

3) HBeAg—anti-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

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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-Ⅰappear 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

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SIGNS AND SYMPTOMS (12)

Fever

Fatigue

Loss of appetite

Nausea

Vomiting

Abdominal pain

Dark urine

Clay-colored bowel movements

Joint pain

Jaundice

Hepatomegaly

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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.

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CLINICAL FEATURES (12)(13)

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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%

CLINICAL FEATURES

ACUTE HEPATITIS B

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

Phases of disease

1. Preicteric

2. Icteric

3. Convalescent49

Preicteric

a. Tiredness

b. Anorexia

c. Vague abdominal discomfort

d. Nausea & Vomiting

e. Sometime arthralgias & rash

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• 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.

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• 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

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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)

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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.

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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

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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.

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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

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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.

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PLASMA DERIVED VACCINE

These vaccines, derived from the plasma of HBsAg-

positive donors, consist of highly purified, formalin-

inactivated 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.

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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

behavior67

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.

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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.

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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.

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HEPATITIS B VACCINE

ADOLESCENT AND ADULT SCHEDULE

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Dose

Primary 1

Primary 2

Primary 3

Minimum

Interval

- - -

4 weeks

8 weeks*

Usual

Interval

---

1 month

5 months

*third dose must be separated from

first dose by at least 16 weeks

RECOMMENDED DOSE OF HEPATITIS B VACCINE

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Infants and children

<11 years of age

Adolescents 11-19 years

Adults >20 years

Recombivax HB

Dose (mcg)

0.5 mL (5)

0.5 mL (5)

1.0 mL (10)

Engerix-B

Dose (mcg)

0.5 mL (10)

0.5 mL (10)

1.0 mL (20)

Factors for decreased vaccine response:

- Smoking

- Obesity

- HIV infection

- Imunocompromised patients

-Haemodialysis

- Prematurity

- Genetic factors

- Chronic disease.

- Subcutaneous injection

- Freezing of vaccine

- Accelerated schedule

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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 Sjorgren’s syndrome

o lichen planus

o glossitis and/or angular cheilosis

o Mucosal Ecchymosis

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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.

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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.

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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.

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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.

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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.

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In acute hepatitis B the treatment is basically

symptomatic

Rest

Ant emetics to control vomiting

Plenty of fluids and carbohydrates

Hepatotropic agents

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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

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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.

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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.

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