Hepatitis B Virus

2.  General concept
 Definitions of hepatitis
 Hepatitis B virus
 What is hepatitis
 Reservoir
 Causative agent and its structure
 Decoy partial
 Symptoms ,mode of transmission and RF
 Replication
 Epidemiology
 Preventions statistics

3.  Hepatitis = 'inflammation of the liver'.
 six medically important viruses are commonly
described as “hepatitis viruses”:
HAV,HBV,HCV,HDV,HEV,HGV.

5.  Acute: Short term and/or severe.
 Chronic: Lingering or lasting - may or may not be severe
 Fulminant: Developing quickly and lasting a short time,
high mortality rate.
 Cirrhosis: Hardening: may be the result of infection or
toxins (e.g. alcohol)
 Jaundice: Yellowing of the skin, eyes, etc due to raised
levels of bilirubin in the blood due to liver damage.
 Hepatocellular carcinoma ： is closely associated with
hepatitis B, and at least in some regions of the world with
hepatitis C virus.

6. Hepatitis B VirusHepatitis B Virus

7.  What is it?
 Hepatitis B is serious disease caused by a virus
that infect the liver
 Can cause lifelong infection, cirrhosis (liver
scarring), liver cancer, liver failure and death
Hepatitis B

8.  Humans are the reservoir.

9.  Causative agent is Hep B virus
 Family: Hepadnaviridae
 Hepa: for liver
 Dna: for Deoxyribonucleic acid
 Virion (aka Dane particle):
 Outer lipid envelope
 Icosahedral nucleocapsid core composed of protein
 Outer envelope proteins:
 Binding & entry into susceptible cells
 Size: small, 42 nm in diameterStructure

10. HBVHBV : Structure: Structure

11. Dane particleDane particle
HBsAg = surface (coat) protein
HBcAg = inner core protein (a single serotype)
HBeAg = secreted protein; function unknown

12.  HBsAg-containing
particles are released into
the serum of infected
people and outnumber the
actual virions.
 Spherical or filamentous
 They are immunogenic and
were processed into the
first commercial vaccine
against HBV.

14.  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

15. Replication of HBV

17.  High (>8%): 45% of global population
 lifetime risk of infection >60%
 early childhood infections common
 Intermediate (2%-7%): 43% of global population
 lifetime risk of infection 20%-60%
 infections occur in all age groups
 Low (<2%): 12% of global population
 lifetime risk of infection <20%
 most infections occur in adult risk groups
Global Patterns of Chronic HBV Infection

18.  Nausea
 Loss of appetite
 Vomiting
 Fatigue
 Fever
 Dark urine
 Pale stool
 Jaundice
 Stomach pain
 Side pain
 A person may have all, some or none of these

19.  Parenteral - IV drug abusers, health workers are
at increased risk.
 Sexual - sex workers and homosexuals are
particular at risk.
 Perinatal(Vertical) - mother(HBeAg+) →infant.
HBV:HBV: Modes of TransmissionModes of Transmission

20.  Injection drug users
 Sex partners of those with Hep B
 Sex with more than one partner
 Men who have sex with men
 Living with someone with chronic Hep B
 Contact with blood
 Transfusions, travel, dialysis

21. High Moderate
Low/Not
Detectable
blood semen urine
serum vaginal fluid feces
wound exudates saliva sweat
tears
breastmilk
Concentration of Hepatitis B Virus
in Various Body Fluids

22.  Virus enters hepatocytes via blood
 Immune response (cytotoxic T cell) to viral
antigens expressed on hepatocyte cell surface
responsible for clinical syndrome
 5 % become chronic carriers (HBsAg> 6 months)
 Higher rate of hepatocellular ca in chronic
carriers, especially those who are “e” antigen
positive
 Hepatitis B surface antibody likely confers
lifelong immunity (IgG anti-HBs)
 Hepatitis B e Ab indicates low transmissibility

23. Incubation period: Average 60-90 days
Range 45-180 days
Insidious onset of symptoms.
Tends to cause a more severe disease than Hepatitis A.
Clinical illness (jaundice): <5 yrs, <10%
≥ 5 yrs, 30%-50%
1/3 adults-no symptoms
Clinical Illness at presentation 10 - 15%
Acute case-fatality rate: 0.5%-1%
Chronic infection: < 5 yrs, 30%-90%
≥ 5 yrs, 2%-10%
More likely in ansymptomatic infections
Premature mortality from
chronic liver disease: 15%-25%

24. Possible Outcomes of HBV InfectionPossible Outcomes of HBV Infection
Acute hepatitis B infection
Chronic HBV infection
3-5% of adult-
acquired infections
95% of infant-
acquired infections
Cirrhosis
Chronic hepatitis
12-25% in 5 years
Liver failureHepatocellular
carcinoma
Liver transplant
6-15% in 5 years 20-23% in 5 years
DeathDeath

25.  Most healthy adults (90%) who are infected
will recover and develop protective
antibodies against future hepatitis B infections
 90% of infants and up to 50% of young
children infected with hepatitis B will
develop chronic infections.

26.  2 billion people have been infected (1 out of 3
people).
 400 million people are chronically infected.
 10-30 million will become infected each year.
 An estimated 1 million people die each year
from hepatitis B and its complications.
 Approximately 2 people die each minute from
hepatitis B.

27.  12 million Americans have been infected (1 out
of 20 people).
 More than one million people are chronically
infected .
 Up to 100,000 new people will become infected
each year.
 5,000 people will die each year from hepatitis B
and its complications.
 Approximately 1 health care worker dies each
day from hepatitis B.

28.  1.3 billion people
 the world's largest population of hepatitis B
patients, with nearly half a million people
dieing of the liver disease every year
 120 million Chinese have tested positive for
hepatitis B, which has become a severe public
health problem in the country

29.  350,000,000 carriers worldwide
 120,000,000 carriers in China
- the carrier rate can exceed 10%
-15 to 25% of chronically infected patients will die
from chronic liver disease
 500,000 deaths/year in China
 982,297 liver disease in China 2005
 50% of children born to mothers with chronic HBV
in the US are Asian American

30.  Interferon alfa (Intron A) Response rate
is 30 to 40%.
 Lamivudine (Epivir HBV) (relapse
,drug resistance)
 Adefovir dipivoxil (Hepsera)

31.  Vaccination
- highly effective recombinant vaccines
 Hepatitis B Immunoglobulin (HBIG)
-exposed within 48 hours of the incident/ neonates
whose mothers are HBsAg and HBeAg positive.
 Other measures
-screening of blood donors, blood and body fluid
precautions.