HBV

1. PAPER-203

2.  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.

3.  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

4.  Hepatitis = 'inflammation of the liver'.
 Hepatitis may be caused by a variety of viruses or other infections,
medications, or a toxin such as alcohol. Hepatitis viruses that can
cause injury to liver cells in addition to hepatitis B include the
hepatitis A and hepatitis C viruses.
 six medically important viruses are commonly described as “hepatitis viruses”:
 HAV, HBV, HCV, HDV, HEV, HGV.
 These viruses are not related to each other or to the hepatitis B virus,
and they differ in their structure, the ways they are spread among
individuals, the severity of symptoms they can cause, the way they are
treated, and the outcome of the infection. Other hepatitis viruses
(hepatitis D, hepatitis E, and hepatitis G) cause disease much less
commonly.

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.

7. Hepatitis B VirusHepatitis B Virus

8.  a member of the hepadnavirus group
 Circular partially double-stranded DNA
viruses
 Replication involves a reverse transcriptase.
 endemic in the human population and
hyperendemic in many parts of the world.
 a number of variants
 It has not yet been possible to propogate the
virus in cell culture

9. HBVHBV : Structure: Structure

10.  Virion also referred to as Dane particle (ds-tranded
DNA)
 42nm enveloped virus
 Core antigens located in the center (nucleocapsid)
* Core antigen (HBcAg)
* e antigen (HBeAg)- an indicator of transmissibility
(minor component of the core- antigenically distinct
from HBcAg)
 22nm spheres and filaments other forms- no DNA in
these forms so they are not infectious (composed of
surface antigen)- these forms outnumber the actual
virions

11. Dane particleDane particle
HBsAg = surface (coat) protein ( 4 phenotypes : adw, adr, ayw and ayr)
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.

13.  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

14. Replication of HBV

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

16.  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

17. 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

18.  People from endemic regions
 Babies of mothers with chronic HBV
 Intravenous drug abusers
 People with multiple sex partners
 Hemophiliacs and other patients requiting
blood and blood product treatments
 Health care personnel who have contact with
blood
 Residents and staff members of institutions for
the mentally retarded

19.  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

20. 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%

21. 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

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

24.  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.

25.  Infants: several options that depend on status of
the mother
• If mother HBsAg negative: birth, 1-2m,6-18m
• If mother HBsAg positive: vaccine and Hep B
immune globulin within 12 hours of birth, 1-2m, <6m
 Adults
* 0,1, 6 months
 Vaccine recommended in
• All those aged 0-18
• Those at high risk

26.  General concepts for hepatitis
 Types of hepatitis
 Properties of HBV : Structure ORFReplication
 Transmission Epidemiology
 Pathogenesis & Immunity
 Clinical Features
 Laboratory Diagnosis
 Treatment Prevention

27.  What is hepatitis B?
 What are the properties of HBV?
 How many ORFs of HBV?
 How is HBV spread?
 How does the HBV curse the liver diseases?
 How do you interpret serological lab results
for HBV?
 How to treat and prevent hepatitis B?

28.  Following transmission of HBV from mother to
infant, which of the following is the most
common medical problem for the infant?
A. Liver failure.
B. Chronic HBV carrier state
C. Development of lymphoma.
D. Opportunistic infections.
E. Development of CNS disease.

29.  Because there are more Asian people already
infected with hepatitis B than Westerners.
Although hepatitis B is not an "Asian disease", it
affects hundreds of millions of Asians. Since the
Asian community starts with such a large
number of infected people, there are more
people who can pass the hepatitis B virus on to
others.This increases the risk that you could
get infected. Since there is a smaller number of
Westerners who are infected, this group has a
lower risk of infection

30.  People who are unable to get rid of the hepatitis
B virus are diagnosed as being a "chronic
carrier".
 The virus can stay in their blood and liver for a
long time.
 They can unknowingly pass the virus on to other
people.
 Chronic hepatitis B can also lead to serious liver
diseases, such as cirrhosis or liver cancer. Not
every chronic carrier will develop serious liver
disease.
 However, they have a greater chance than
someone who is not infected.

31.  The good news is that you can break the cycle of
infection in your family and in the Chinese
community.
 Get tested for hepatitis B.
 Make sure everyone in your family is vaccinated
against hepatitis B.
 Get the vaccine yourself.
 Look for good medical care.
 Discuss treatment options with your family
doctor or a liver specialist if you already have
chronic hepatitis B.

32.  Currently, there are five approved drugs in the United
States for people who have chronic hepatitis B infections.
These drugs are also available in China:
 1 、 Epivir-HBV or Zeffix (lamivudine) is a pill that is taken
orally
 2 、 Hepsera (adefovir dipivoxil) is a pill that is taken orally
 3 、 Baraclude (entecavir) is a pill that is taken orally
 4 、 Intron A (interferon alpha) is a drug given by injection
 5 、 Pegasys (pegylated interferon) is a drug that is give by
injection

33.  It is important to know, not every chronic hepatitis B
patient needs to be on medication.
 Some patients only need to be monitored by their
doctor on a regular basis (at least once a year, or
more).
 Other patients with active signs of liver disease may
benefit the most from treatment.
 Be sure to talk to your doctor about whether you could
benefit from treatment and discuss the treatment
options.
 In addition, there are promising new drugs in clinical
trials and in the research pipeline.
 However, it is vital that all people with chronic
hepatitis B visit their doctor on a regular basis,
whether they receive treatment or not!