Upendra Thapa Shrestha

© U. T. Shrestha

Hepatitis
 Viral hepatitis is a systemic disease primarily involving liver
due to a viral infection.
 It may present in acute (recent infection, relatively rapid
onset) or chronic forms.
 The most common causes of viral hepatitis are the five
unrelated hepatotropic viruses Hepatitis A, Hepatitis B,
Hepatitis C, Hepatitis D, and Hepatitis E.
 In addition to the nominal hepatitis viruses, other viruses that
can also cause liver inflammation include Cytomegalovirus,
Epstein–Barr virus, and Yellow fever virus, herpes simplex
virus, rubella virus, and the enteroviruses

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 Hepatitis viruses produce acute inflammation of the liver,

resulting in a clinical illness characterized by fever,
gastrointestinal symptoms such as nausea and vomiting,
and jaundice.
 Regardless of the virus type, identical histopathologic
lesions are observed in the liver during acute disease.
 Most of these diseases spread very fast because infected
individuals are contagious not only during stage of
manifestation of the disease but also during the phase of
incubation.

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HEPATITIS B & HBV

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Hepatitis B
 Hepatitis B is a viral infection of liver caused by Hepatitis
B virus, abbreviated HBV, a species of the genus
Orthohepadnavirus, which is likewise a part of the
Hepadnaviridae family of viruses.
 HBV can establishes chronic infections and it is a major
factor in the eventual development of liver disease and
hepatocellular carcinoma

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Virus classification

Group: Group VII (dsDNA-RT)

Order: Unassigned
Family: Hepadnaviridae

Genus: Orthohepadnavirus

Species: Hepatitis B virus

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History
 The serum hepatitis was used after an outbreak of
hepatitis among American soldiers in 1942.
 The cause of outbreak was linked to yellow fever
vaccine that was given to the soldiers which was
contaminated by human serum.
 Blumberg and his colleagues in 1965 described the
Australian antigen which was later called as
hepatitis B surface antigen (HBsAg).
 DS Dane in 1970 was first to describe hepatitis B viral
particle in human serum in electron microscopy.
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Hepatitis B Virus (HBV)

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Structure…

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Important Properties of Hepadnaviruses

Virus structure Characteristic features
Virion About 42 nm in diameter overall (nucleocapsid; 18 nm)
Genome One molecule of double stranded DNA, circular, 3.2 Kbp. In
virion negative DNA strand is full length and positive DNA
is partially complete. The gap must be beginning of
replication cycle
Proteins Two major polypeptides (one glycosylated) are present in
HBsAg; one polypeptide is HBcAg
Envelop Containing HBsAg and lipid
Replication By means of an intermediate RNA copy of the DNA genome
(HBcAg in cytoplasm). Both mature virus and 22-nm
spherical particles consist of HBsAg secreted from the cell
Outstanding Family is made up of many types that infect humans and
characteristics lower animals (e.g. woodchucks, squirrels, ducks)
Cause acute and chronic hepatitis, often progressing to
permanent carrier states and hepatocellular carcinoma. 10
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Structure and composition of HBV

 Electron microscopy of HBsAg-positive serum reveals
three morphologic forms of the virus.
 The most numerous are spherical particles measuring 22
nm in diameter
 These small particles are made up exclusively of HBsAg–
–as are tubular or filamentous forms, which have the
same diameter but may be over 200 nm long––and result
from overproduction of HBsAg (Hepatitis B surface
antigen).
 Larger, 42-nm spherical virions (originally referred to as
Dane particles) are less frequently observed

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Schematic representation of three HBsAg-containing forms

that can be identified in serum from HBV carriers

The 42-nm spherical

Dane particle can be
disrupted by nonionic
detergents to release
the 28-nm core that
contains the partially
double-stranded viral
DNA genome. A
soluble antigen, termed
HBeAg, may be
released from core
particles by treatment
with strong detergent.

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 The outer surface, or envelope, contains HBsAg and

surrounds a 27-nm inner nucleocapsid core that contains
HBcAg (Hepatitis B core antigen).
 The particles containing HBsAg are antigenically
complex.
 Each contains a group-specific antigen, a, in addition to
two pairs of mutually exclusive subdeterminants, d/y and
w/r.
 Thus, four phenotypes of HBsAg have been observed:
adw, ayw, adr, and ayr.

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HBV GENOME
Genetic organization of the
HBV genome. Four open
reading frames encoding
seven peptides are indicated by
large arrows. Regulatory
sequences (promoters [prom],
enhancers [Enh], and
glucocorticoid responsive
element [GRE]) are marked.
Only the two major transcripts
(core/pre-genome and S
mRNAs) are represented. DR1
and DR2 are two directly
repeated sequences of 11 bp at
the 5' extremities of the minus-
and plus-strand DNA.

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GENOME…..
 The genome of HBV is made of circular DNA, but it is
unusual because the DNA is not fully double-stranded.
 One end of the full length strand is linked to the viral
DNA polymerase.
 The genome is 3020–3320 nucleotides long (for the full-
length strand) and 1700–2800 nucleotides long (for the
short length-strand).
 The negative-sense (non-coding) is complementary to the
viral mRNA.
 The viral DNA is found in the nucleus soon after infection
of the cell.
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GENOME……
 The partially double-stranded DNA is rendered fully double-
stranded by completion of the (+) sense strand and removal of a
protein molecule from the (−) sense strand and a short sequence of
RNA from the (+) sense strand.
 Non-coding bases are removed from the ends of the (−) sense
strand and the ends are rejoined.
 There are four known genes encoded by the genome, called C, X,
P, and S.

Gene C
 The core protein is coded for by gene C (HBcAg), and its start
codon is preceded by an upstream in-frame AUG start codon from
which the pre-core protein is produced.
 HBeAg is produced by proteolytic processing of the pre-core
protein.
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GENOME……
 In some rare strains of the virus known as Hepatitis B virus
precore mutants, no HBeAg is present

Gene P
 The DNA polymerase is encoded by gene P.

Gene S
 Gene S is the gene that codes for the surface antigen
(HBsAg).
 The HBsAg gene is one long open reading frame but
contains three in frame "start" codons that divide the gene
into three sections, pre-S1, pre-S2, and S. 17
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GENOME……
 Because of the multiple start codons, polypeptides of three
different sizes called large, middle and small (S) are
produced.

Gene X
 The function of the protein coded for by gene X is not fully
understood but it may function as a transcriptional
transactivator* and is associated with the development of
liver cancer.
 * It stimulates genes that promote cell growth and
inactivates growth regulating molecules
 The viral genes are transcribed by the cellular RNA
polymerase II in the cell nucleus from a covalently closed
circular DNA (cccDNA) template. 18
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Enhancers
 Two enhancers designated enhancer I (EnhI) and enhancer II
(EnhII) have been identified in the HBV genome.
 Both enhancers exhibit greater activity in cells of hepatic
origin, and together they drive and regulate the expression of
the complete viral transcripts

Non-coding RNA elements

 Several non-coding RNA elements have been identified in the
HBV genome.
 These include: HBV PRE-alpha, HBV PRE-beta and HBV
RNA encapsidation signal epsilon
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Genotypes and sub-genotypes

 The viral strains have also been divided into ten
genotypes (A–J) and forty sub-genotypes according
to overall nucleotide sequence variation of the genome.
 The genotypes have a distinct geographical
distribution and are used in tracing the evolution and
transmission of the virus.
 Differences between genotypes affect the disease
severity, course and likelihood of complications, and
response to treatment and possibly vaccination.
 The serotypes and genotypes do not necessarily
correspond.
 Genotype D has 10 sub-genotypes. 20
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Disinfection & Inactivation of HBV

 The virus is stable at 37°C for 60 minutes and remains viable
after being dried and stored at 25°C for at least 1 week.
 HBV (but not HBsAg) is sensitive to higher temperatures (100
°C for 1 minute) or to longer incubation periods (60°C for 10
hours).
 HBsAg is stable at pH 2.4 for up to 6 hours, but HBV infectivity
is lost.
 Sodium hypochlorite, 0.5% (e. g.; 1:10 chlorine bleach),
destroys antigenicity within 3 minutes at low protein
concentrations, but undiluted serum specimens require higher
concentrations (5%).
 HBsAg is not destroyed by ultraviolet irradiation of plasma or
other blood products, and viral infectivity may also resist such
treatment. 21
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HVB Replication

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HBV replication cycle:

 HBV virion attaches specifically to the hepatocytes, by
interacting with several receptors.
 HBV attachment to a receptor on the surface of hepatocytes
occurs via a portion of the pre-S region of HBsAg.
 HBV enters the cell through caveolae-mediated
endocytosis.
 Caveolae are specialized lipid rafts that form 50-70 nm
flask-shaped invaginations of the plasma membrane.
 The virion is presumably internalized in the caveolae upon
binding to host receptors, and subsequently delivered to the
early endosome.
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Caveolae-mediated endocytosis
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 The latter matures into late endosome, accompanied by

a pH acidification down to pH 6.0 and uncoating
occurs by fusion of virion membrane with endosomal
membrane and the nucleocapsid is released into cytosol.
 HBV capsids are about 35nm large and use an active
transport along microtubules to reach the cell nucleus.
 The HBV virion-derived or intracellular capsid binds
nuclear trafficking proteins, thereby entering the nuclear
pore.
 It is retained in the nuclear basket where it may
disassemble and release the genomic rcDNA (relaxed
circular DNA) into the nucleus.
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 The cccDNA is generated from the viral polymerase

linked relaxed circular DNA (rc DNA) by DNA repair
proteins of the host.
 The cccDNA is then bound to cellular histones proteins,
forming minichromosome.

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From rcDNA to cccDNA

 The formation of the cccDNA from the rcDNA is incompletely
understood, but several steps are essential for the synthesis:
 The removal of the polymerase covalently attached to the 5’ end
of the negative strand.
 The removal of the primer from the 5’ plus strand.
 The removal of the short redundancy region r from the minus
strand.
 Fill in gaps in the positive strand.
 Fill in gaps at the ends of both strands which must be ligated to
yield closed circles.

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 HBV core protein (HBc) is a component of the HBV

minichromosome with a strong binding affinity to HBV
double-stranded DNA.
 Persistent HBV replication is associated with a high
frequency of integration of HBV sequences into the human
host genome while a lower frequency is observed during
acute hepatitis B infections. They are present in over 85 to
90% of HBV related Hepatocellular carcinomas (HCCs) and
usually precede development of HCC.
 The viral genes are transcribed by the cellular RNA
polymerase II in the cell nucleus from a covalently closed
circular DNA (cccDNA) template producing HBV mRNAs
and the 3.5-kb RNA pre-genome.
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*Mitochondrial antiviral-signaling protein

 The X mRNA seems to be transcribed early and transiently,

whereas structural proteins mRNAs are on the contrary
expressed later and constantly.
 HBx i.e. product of X mRNA guaranties optimal replication
conditions by overcoming host cell defenses, regulating viral
replication and modulating host cell signaling pathways and
genes expression. The protein has been associated with
numerous functions in and out of the nucleus, and numerous
protein-protein interactions.
 The two main functions are: in the nucleus HBx promotes
the viral minichromosome transcription; in the cytoplasm
HBx degrades MAVS* in the mitochondria which has a
potent antiviral action in hepatocytes.
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 Viral RNAs are then exported to the cytosol.

 The pre-genome is encapsidated by a packaging signal
located near the 5' end of the RNA into newly synthesized
core particles, where it serves as template for the HBV
reverse transcriptase encoded within the polymerase
gene.
 An RNase H activity of the polymerase removes the RNA
template as the negative-strand DNA is being synthesized.
 DNA is made double stranded by DNA polymerase and
this DNA becomes the genome for the Newly forming
virions.
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 Double-strand formation ceases when the virions bud from

the host cell, generally leaving part of the genome single-
stranded.
 Positive-strand DNA synthesis does not proceed to
completion within the core, resulting in replicative
intermediates consisting of full-length minus-strand DNA
plus variable-length (20–80%) positive-strand DNA.
 Core particles containing these DNA replicative
intermediates bud from pre-Golgi membranes (acquiring
HBsAg in the process) and may either exit the cell or
reenter the intracellular infection cycle.

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Pathogenesis of HVB infection

 Hepatitis B virus, after entering the blood, infects the
hepatocytes in the liver with the expression of viral
antigen on the surface of infected cells.
 CD4 and CD8 lymphocytes, recognize various HBV-
derived proteins present on the surface of hepatocytes
resulting in an immunological reaction.
 A chronic carrier stage with HBV infection is an
important event in the pathogenesis of HBV infection.
 A person with chronic carrier stage has HBsAg persisting
in the blood for at least 6 months.

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 This stage is caused by a persistent infection of the

hepatocytes that leads to the presence of HBV and HBsAg
in the blood.
 This chronic carrier stage occurs in about 5% of patients
with HBV infection in contrast to no chronic carrier stage
in patients with HAV infection
 In an infected host whether the person will become a
chronic carrier state or will be free of infection depends on
the cytotoxic T-cell response.
 If the cytotoxic T-cell response is strong, the infection is
cleared in the person but if the response is inadequate, the
person becomes a chronic carrier.

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 During the chronic stage, the HBV DNA is present in episome

in the cytoplasm of persistently infected cells, and in some
cells the viral DNA is integrated with cellular DNA.
 Chronic carrier state is more likely to occur when infection
occurs in a newborn than in adult. It has been observed that
approximately 90% of the infected neonates become chronic
carriers.
 Approximately 20% of HBsAg carriers, nearly 1% of all
adult patients infected with HBV, and high percentage of
neonates infected with the virus progress to develop
hepatocellular carcinoma or cirrhosis.

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 The hepatocellular carcinoma appears to be the result of

persistent cellular regeneration that tends to replace the
dead hepatocytes.
 Also it is suggested that the integration of HBV DNA with
hepatocytes DNA could activate a cellular oncogene,
resulting in loss of control of the growth of hepatocytes.
 However, the HBV genome has no oncogene which can be
responsible directly for causing hepatocellular carcinoma.

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Host Immunity
 Hepatitis B virus natural infection induces a lifelong
immunity.
 The immunity is primarily mediated by humoral
antibodies against HBsAg.
 Antibodies to HBsAg are protective.
 These antibodies bind to surface antigens or with the virus
and prevent it from interaction with receptors on the
hepatocytes.
 These antibodies appear to neutralize the infectivity of
HBV.
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 But the antibodies against core antigen HBcAg are not

protective because the antibodies cannot act with
HBcAg present inside the cells.

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Clinical Syndromes
 Hepatitis B virus is one of the most important causes of
acute and chronic hepatitis.
 The clinical manifestations vary from subclinical hepatitis
to symptomatic and icteric hepatitis.
 The incubation period varies from 6 weeks to 6 months.
 The clinical manifestations of HBV infection depend on
(a) age of infection,
(b) immune status of the host, and
(c) the level of HBV.

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Acute hepatitis B virus infection

 The prodromal or pre-icteric phase is characterized by
gradual onset of anorexia, malaise, and fatigue.
 During the icteric phase, the liver becomes tender with
development of jaundice.
 Nausea, vomiting, and pruritus with passing of dark-
colored urine are the symptoms noted in this stage.
 Clinical manifestations of acute hepatitis B are similar to that
of hepatitis A but with the difference that the symptoms tend
to be more severe and life-threatening with HBV
infection.
 The clinical disease associated with acute HBV infection
may range from mild disease to a disease as severe as
fulminant hepatitis occurring in less than 1% of the
patients.
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Chronic hepatitis B virus infection

 Chronic HBV infection is one of the major
complications of HBV infection.
 The risk of chronic infection is also higher in those
infected at birth (90%) and in patients who are
immuno-compromised.
 Only 5–10% of older children or adults progress to
develop chronic infection.

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Complications of Hepatitis B virus infection:

 Cirrhosis and hepatocellular carcinoma are the long-
term but rare complications of hepatitis B.
 Perinatal transmission or infection in children is
associated with few or no symptoms, but infection
has a high risk of becoming chronic.
 Fulminant hepatic failure is another major
complication of HBV infection.
 This condition occurs in approximately 0.5–1% of
HBV-infected patients. The condition progresses to
fulminant hepatic failure with coagulopathy,
encephalopathy, and cerebral edema.
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 The case fatality rate of these patients is very high nearing

80%.
 Patients with chronic HBV infection have a very high risk of
developing hepatocellular carcinoma.
 The cancer appears to be due to repeated episodes of chronic
inflammation and cellular regeneration.
 The cancer that develops an average of 25–30 years after
initial infection is the leading cause of cancer-related deaths
in areas where HBV is endemic.
 Glomerulonephritis, polyarteritis nodosa*, varieties of skin
manifestations, cardiopulmonary manifestations, and joint and
neurologic manifestations are other important complications of
HBV infection.
*is a systemic vasculitis of small- or medium-sized muscular
arteries
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Reservoir, Source and Transmission of Infection

 Individuals with chronic HBV infection are the major
reservoir of HBV infections.
 These people with HBeAg in their serum tend to have
high viral titers and thus greater infectivity.
 Hepatitis B virus is present at a high level in serum.
 The virions are also present at very low levels in semen,
vaginal mucosa, saliva, and tears, and all are
infectious.
 The virus is not detected in urine, stool, or sweat;
hence these specimens are not infectious.

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 The hepatitis B virus can be transmitted in the

following ways:

Perinatal transmission:
 This is the major route of transmission of the virus
worldwide.
 The transmission occurs from infected mother to
child due to contact with mother’s infected blood
during the time of delivery as opposed to
transplacental passage of the virus.
 Although HBV is found in breast milk, the role of
breast-feeding in transmission is unclear

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Parenteral transmission:
 This transmission occurs due to transfusion of HBV-
infected blood and blood products.
 This was one of the important modes of transmission
before 1970s, but with the starting of screening of blood
donors for HBsAg, the rate of blood transfusion
associated HBV infection has reduced considerably
worldwide.
 Patients with hemophilia, renal dialysis, and those
receiving organ transplantation and intravenous drug
users remain at increased risk of infection.
 The risk of acquiring HBV among health workers after
needle stick injury from infected individuals is estimated
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to be as high as 5%.
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Sexual transmission of HBV:

 Hepatitis B virus is transmitted sexually more easily than
Hepatitis C virus (HCV) or Hepatitis D virus (HDV).
 The infection is associated with vaginal intercourse,
genital rectal intercourse, and non-genital intercourse.
 Health workers with exposure to infected blood or body
fluids, heterosexual persons with multiple partners,
household contact, or sexual partners of HBV carriers
are other groups at risk.

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Laboratory Diagnosis
 Laboratory diagnosis plays an important role to confirm
the HBV etiology of hepatitis.
Specimen
 Serum is an important specimen because definitive
diagnosis of HBV depends on serological testing for
HBV infections.

Serodiagnosis
 Diagnosis of acute infection is made by demonstration of
HBsAg as well as HBeAg in the serum.
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 Both HBsAg and HBeAg are the important serum

markers of acute HBV.
 They indicate viral replication.
 When viral replication slows, HBeAg disappears and
anti-HBeAg is detected.
 Hepatitis B surface antibody (HBsAb) produced may
persist for many years.
 This is followed by demonstration of IgM antibodies
against hepatitis B core antigen (HBcAb).

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Clinical and serologic events occurring in a patient with acute

hepatitis B virus infection

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HBsAg:
 The antigen appears in blood during incubation
period and is detectable in most patients during
prodrome and acute phase of the disease.
 Persistent presence of HBsAg in blood for at least 6
months indicates the carrier state and also indicates
the risk of chronic hepatitis and hepatic carcinoma.
 It is not detectable in the serum during
convalescent stage.
 The presence of HBsAg alone does not necessarily
indicate replication of complete virion, and the
patients may not have symptoms of liver damage.
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HBsAb:
 HBsAb is a protective antibody that neutralizes the virus
and is usually not detectable during the acute disease
since it forms immune complex with HBsAg because it is
bound to the large amount of HBsAg present in blood.
 It is also not detectable in the chronic carrier stage.

HBcAb:
 Demonstration of HBcAb is useful to confirm the
diagnosis of HBV infection.
 Total HBcAb including IgM and IgG antibodies indicates
exposure to the virus and viral replication.
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 The HBcAb appears shortly after HBsAg in acute disease

and persists for life.
 Detection of IgM HBcAb is diagnostic of acute HBV
infection during window phase.
 The HBcAb are present in individuals with acute
infection, chronic infections, and also in those who have
recovered from acute infection.
 Therefore, the presence of HBcAb IgG does not
differentiate between acute and chronic infection.
 HBcAg is not detectable in the serum, but can be
demonstrated in the liver cells by immunofluorescence.

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HBeAg:
 HBeAg is present in the blood during the incubation and
also during the prodrome and early acute disease.
 This is also present in certain chronic carriers.
 The presence of HBeAg indicates a high likelihood of
infectivity and transmissibility.
 Chronic replication of HBV is characterized by the
presence of circulating HBsAg, HBeAg usually with
HBcAg.
 Both HBsAg and HBeAg are not present in serum during
convalescence.
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 Serum IgG antibodies to HBsAg, HBcAg, and HBeAg

appear during the stage of convalescence.
 In essence, hepatitis B serology is useful to describe the
course and nature of the disease.
 Acute and chronic HBV infection can be differentiated by
the presence of HBsAg and HBeAg in the serum and
distribution pattern of the antibodies to the individuals’
HBV antigen

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Hepatitis B virus DNA and DNA polymerase

 Hepatitis B virus DNA and DNA polymerase activity are
detectable during the incubation period and early in the disease.
 HBV DNA levels are typically low or absent in inactive carriers.
 HBV DNA levels are higher in patients with chronic hepatitis and
are associated with increased infectivity.
 The detection of viral DNA in the serum indicates acute infection.
 HBV PCR for demonstration of HBV DNA is highly valuable to
monitor the treatment of chronic HBV infection with antiviral
therapy.
 This is also useful to identify HBV as the cause of liver infection
in HBsAg-negative patients.

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Other tests
 These tests include elevation of ALT and AST.
 High levels are found in acute hepatitis (1000–2000
IU/mL).
 Estimation of serum bilirubin indicates the intensity of
jaundice.

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Treatment
 No specific antiviral treatment is available for patients with
acute HBV infection.
 Supportive and symptomatic care continues to be the
mainstay of therapy for most of the patients.
 Therapy is recommended for patients with chronic hepatitis
B infection.
 Interferon and nucleoside analogs, such as Lamivudine,
Adefovir, and Telbivudine are the antiviral drugs used
widely.
 These antiviral drugs achieve viral suppression as
demonstrated by loss of HBeAg in serum and suppression
of HBV DNA. 57
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Interferons:
 Interferon-alpha (IFN-α) has been the mainstay in
treatment of chronic hepatitis B since its introduction in
mid-1980s.
 Interferon acts by immunomodulation and prevents
progression of acute hepatitis to chronic stage.
 It also promotes more rapid resolution of viremia and
normalization of serum aminotransferase levels.
Nucleoside analogs:
 These block the replication of viruses by directly blocking
the replication of HBV.
 These nucleoside analogs are highly effective against HBV,
and are bioavailable and extremely well targeted. 58
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 However, neither interferon nor nucleoside analogs cure

HBV infection.
 The goal of antiviral therapy is only to reduce morbidity
due to HBV and to prevent complications.

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Prevention and Control

 Hepatitis B infection can be prevented by the use of
either vaccine or hyper-immunoglobulin or both

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Vaccines:
 Hepatitis B infection is one of the major diseases of humans that
can be prevented with vaccination.
 Plasma-derived and recombinant DNA HBV vaccines are the
two types of vaccines that use HBsAg to stimulate the production
of anti-HBs in non-infected individuals.
 The vaccines are highly effective with more than 95% of
seroconversion.
 The vaccine for adults is recommended at 0, 1, and 6 months
and for infants at the time of birth, at 1–2 months, and at 6–
18 months.
 The vaccine is indicated for all infants and for all people who are
at high risk of infection.
 The high-risk group includes the people who are frequently
exposed to blood and blood products, patients receiving
multiple transfusion or dialysis, patients suffering from
sexually transmitted disease, and intravenous drug users.
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Hepatitis B Immunoglobulin
 Hepatitis B immunoglobulin (HBIg) is used for passive
immunization of patients after or just before the exposure.
 This immunoglobulin is derived from human plasma and
contains high titer of HBsAb. It is prepared from plasma from
patients who have recovered from hepatitis B infection.
 Passive immunization with HBIg is recommended for:
 people who have a history of recent exposure to patient(s) infected with
HBV,
 a household contact with acutely infected patient,
 sexual contact with an acutely infected patient, and
 infants born to HBsAg-positive mother.

 Screening of blood and blood products for HBsAg is important

to prevent transfusion-related HBsAg.
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According to WHO………
 WHO recommends that all blood donations be tested for
hepatitis B to ensure blood safety and avoid accidental
transmission to people who receive blood products.
 Acute HBV infection is characterized by the presence of
HBsAg and immunoglobulin M (IgM) antibody to the
core antigen, HBcAg.
 During the initial phase of infection, patients are also
seropositive for hepatitis B e antigen (HBeAg).
 HBeAg is usually a marker of high levels of replication
of the virus.

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 The presence of HBeAg indicates that the blood and body

fluids of the infected individual are highly contagious.
 Chronic infection is characterized by the persistence of
HBsAg for at least 6 months (with or without concurrent
HBeAg).
 Persistence of HBsAg is the principal marker of risk for
developing chronic liver disease and liver cancer
(hepatocellular carcinoma) later in life.
 WHO recommends the use of oral treatments - Tenofovir
or Entecavir, because these are the most potent drugs to
suppress hepatitis B virus.

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 They rarely lead to drug resistance as compared with

other drugs, are simple to take (1 pill a day), and have
few side effects so require only limited monitoring.

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WHO’s Preventive Strategy

 The hepatitis B vaccine is the mainstay of hepatitis B
prevention.
 WHO recommends that all infants receive the hepatitis B
vaccine as soon as possible after birth, preferably within 24
hours.
 The birth dose should be followed by 2 or 3 doses to complete
the primary series.
 In most cases, 1 of the following 2 options is considered
appropriate: a 3-dose schedule of hepatitis B vaccine, with the
first dose (monovalent) being given at birth and the second and
third (monovalent or combined vaccine) given at the same
time as the first and third doses of diphtheria, pertussis
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 A 4-dose schedule, where a monovalent birth dose is

followed by three monovalent or combined vaccine doses,
usually given with other routine infant vaccines.
 The complete vaccine series induces protective antibody
levels in more than 95% of infants, children and young
adults.
 Protection lasts at least 20 years and is probably lifelong.
 Thus, WHO does not recommend booster vaccination for
persons who have completed the 3 dose vaccination
schedule.

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 All children and adolescents younger than 18 years-old and

not previously vaccinated should receive the vaccine if they
live in countries where there is low or intermediate
endemicity.
 In those settings it is possible that more people in high-risk
groups may acquire the infection and they should also be
vaccinated.

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 They include:
 people who frequently require blood or blood products,
dialysis patients, recipients of solid organ transplantations;
 people interned in prisons;
 persons who inject drugs (IDUs);
 household and sexual contacts of people with chronic HBV
infection;
 people with multiple sexual partners;
 health-care workers and others who may be exposed to
blood and blood products through their work; and
 Travelers who have not completed their hepatitis B vaccination
series, who should be offered the vaccine before leaving for
endemic areas.
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WHO also organizes

World Hepatitis Day
on
July 28
every year to increase
awareness and understanding of
viral hepatitis.
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Questions