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Hepatitis Viruses
SAMUEL AGUAZIM .M.D.
Lange Chapter 41
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HCV- most common cause of post
transfusion hepatitis most prevalent
blood-borne pathogen in the U.S.
HEV: Fatality in pregnant women
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Many viruses cause hepatitis. Of these, five
medically important viruses are commonly
described as “hepatitis viruses”:
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hepatitis A virus (HAV)
hepatitis B virus (HBV)
non-A, non-B viruses, of which hepatitis C
virus (HCV) is the most common
hepatitis D virus (HDV, delta agent)
Hepatitis E virus (HEV).
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HEPATITIS A VIRUS
Disease: HAV causes hepatitis A.
Important Properties:
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enterovirus classified in the picornavirus family.
single-stranded positive polarity RNA genome
nonenveloped icosahedral nucleocapsid
replicates in the cytoplasm of the cell.
known as enterovirus 72.
one serotype
no antigenic relationship to HBV or other hepatitis
viruses.
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HAV Transmission & Epidemiology:
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transmitted by the fecal-oral route.
appears in the feces 2 weeks before the
appearance of symptoms.
Children are the most frequently infected group
summer camps and boarding schools.
fecally contaminated water or food such as
oysters grown in polluted water and eaten raw.
Unlike HBV, HAV is rarely transmitted via the blood,
because the level of viremia is low
chronic infection does not occur.
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Pathogenesis HAV:
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probably replicates in the GI tract and spreads to the
liver via the blood. Hepatocytes are infected.
infection of cultured cells produces no cytopathic
effect.
likely that attack by cytotoxic T cells causes the
damage to the hepatocytes.
no chronic infection occur.
HAV Immune response
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IgM antibody, detectable at the time jaundice
appears followed 1—3 weeks later by the production of
IgG antibody, which provides lifelong protection.
IgM Important in the laboratory diagnosis of hepatitis
A.
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HAV Clinical Findings:
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Fever, anorexia (diminished appetite) nausea, vomiting, and
jaundice are typical.
Dark urine, pale feces, and elevated transaminase levels are seen.
Most cases resolve spontaneously in 2—4 weeks.
short incubation period (3—4 weeks) or ( 15-40 days), in contrast
to that of hepatitis B, which is 10—12 weeks.
Laboratory Diagnosis:
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The detection of IgM antibody is the most important test
Treatment: No antiviral therapy is available.
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HAV Prevention:
a.
Active immunization with a vaccine
containing inactivated HAV is available.
b. Passive immunization with immune serum
globulin prior to infection or early in the
incubation period can prevent or mitigate
the disease.
c. Observation of proper hygiene, eg,
sewage disposal and hand washing after
bowel movements, is of prime importance
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HEPATITIS B VIRUS
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hepadnavirus family.
42-nm enveloped virion, icosahedral nucleocapsid
core containing a partially double-stranded circular DNA
genome.
Important antigens
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surface antigen (HBsAg): protein in the envelope which is
important for laboratory diagnosis and immunization.
core antigen (HBcAg): located in the core (nucleocapsid)
e antigen (HBeAg): located in the core is an important
indicator of transmissibility and active viral replication.
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HBV
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Electron microscopy of a patient’s serum reveals
three different types of particles:
a few 42-nm virions and many 22-nm spheres and
long filaments 22 nm wide, which are composed of
surface antigen.
HBV is the only human virus that produces these
spheres and filaments in such large numbers in the
patient’s blood.
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HBV Transmission &
Epidemiology:
Four main modes of transmission are:
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via blood
during sexual intercourse
perinatally from mother to newborn.
Intravenous ( IV)
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HBV Facts
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found worldwide but is particularly prevalent in Asia.
more than 300 million people are chronically
infected with HBV.
high incidence of hepatocellular carcinoma
(hepatoma) in many Asian countries
Immunization against HBV in Taiwan has significantly
reduced the incidence of hepatoma in children.
HBV vaccine is the first vaccine to prevent a
human cancer.
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HBV Pathogenesis & Immunity:
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After entering the blood, the virus infects
hepatocytes
viral antigens are displayed on the surface of the
cells.
Cytotoxic T cells mediate an immune attack against
the viral antigens
inflammation and necrosis occur.
probably the result of this cell-mediated immune injury
HBV itself does not cause a cytopathic effect.
Antigen-antibody complexes cause some of the
early symptoms, eg, arthritis, and some of the
complications in chronic hepatitis, eg, immunecomplex glomerulonephritis, and vasculitis.
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HBV Chronic Carrier
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Unlike hepatitis A patients, about 5% of patients with hepatitis B
become chronic carriers of HBV.
chronic carrier: someone who has HBsAg persisting in their
blood for at least 6 months.
a persistent infection of the hepatocytes, which results in the
prolonged presence of HBV and HBsAg in the blood.
more likely to occur when infection occurs in a newborn than in
an adult, probably because a newborn’s immune system is less
competent than an adult’s.
90% of those infected as neonates become chronic carriers.
neonatal infection is associated with a high risk of
hepatocellular carcinoma.
Lifelong immunity occurs after the natural infection and is
mediated by humoral antibody against HBsAg
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Chronic Active Hepatitis
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Active inflammation on biopsy
Fibrosis present
May progress to liver cancer
Will lead to cirrhosis
Due to Hep b: Tx with interferon and lamuvidine
Due to Hep c: Tx with interferon and ribavarin
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HBV Clinical Findings:
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Many HBV infections are asymptomatic and are
detected only by the presence of antibody to
HBsAg.
mean incubation period for hepatitis B is 10—12
weeks, which is much longer than that of hepatitis A
(3—4 weeks).
clinical appearance of acute hepatitis B is similar
to that of hepatitis A.
However, with hepatitis B, symptoms tend to be
more severe, and life-threatening hepatitis can
occur.
Most chronic carriers are asymptomatic, but some
have chronic active hepatitis, which can lead to
cirrhosis and death.
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Liver cirrhosis
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consequence of repeated immune system
attacks
cirrhosis cannot be cured
progress may be stopped if the cause is treated
cessation of enzymatic processes in the liver
Ascites, jaundice, internal bleeding, and
hepatic encephalopathy
candidates for liver transplantation
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Fulminant hepatitis
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occurs in 1% of acutely infected
individuals; more likely if HBV and HDV
coinfect.
more severe symptoms, can be fatal
severe liver damage: ascites and bleeding
liver shrinkage
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Primary hepatocellular
carcinoma
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Liver carcinoma follows HBV infection after 935 years
Chronic HCV infection can also result in
hepatocellular carcinoma
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Extrahepatic Findings of HBV
infections
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* Polyarteritis Nodosa
* Membranous nephropathy
* Membranoproliferative glomerulonephritis
type 1.
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On histology
CHRONIC HEPATITIS B
may show pathonomonic
ground glass hepatocyte
inclusions
(arrows heads) which is a
granular homogenous
eosinophilic staining of
cytoplasm caused by
presence of HBsAg
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Laboratory Diagnosis HBV:
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The most important laboratory test for the
detection of early HBV infection is the
immunoassay for HBsAg.
HBsAg appears during the incubation
period, first viral marker detected in the
blood of HBV infection and is detectable in
most patients during the prodrome and acute
disease
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HBeAg
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arises during the incubation period and is present
during the prodrome and early acute disease and
in certain chronic carriers.
HBeAg has a high correlation with DNA
polymerase activity.
presence is an important indicator of
transmissibility, and, conversely
finding
of
HBeAb
indicates
low
transmissibility
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HBcAg
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found within the nuclei of infected
hepatocytes
not generally in peripheral circulation except
as an integral component of Dane particle.
Anti-HBc may be the only detected
serologic
marker
during
the
early
convalescent phase of an HBV infection
“window phase”.
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HBV Treatment:
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Alpha interferon is clinically useful for the treatment of chronic
hepatitis B infections.
Lamivudine that inhibit the reverse transcriptase of HIV also
effective against the DNA polymerase of HBV.
HBV Prevention:
 involves the use of either the vaccine or hyperimmune globulin or
both.
(1)The vaccine, eg, Recombivax, contains HBsAg as the
immunogen. Second generation vaccine is using recombinant
DNA.
(2) Hepatitis B immune globulin (HBIG) contains a high titer of
HBsAb because it is prepared from sera of patients who have
recovered from hepatitis B.
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Vaccine Recommended
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Newborns/youth
Healthcare Workers
IV drug users
Individual with multiple sexual partners
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NON-A, NON-B HEPATITIS
VIRUSES
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describes the cases of hepatitis for which
existing serologic tests had ruled out all
known viral causes.
term is not often used because the main
cause of non-A, non-B hepatitis, namely,
hepatitis C virus, has been identified.
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HEPATITIS C VIRUS
Disease: HCV causes hepatitis C.
Important Properties:
 enveloped virion containing a genome of
single-stranded, positive-polarity RNA.
 member of the flavivirus family.
 no virion polymerase.
 Multiple serotypes exist.
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HEPATITIS C VIRUS
Transmission & Epidemiology:
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transmitted via blood.
most common cause of posttransfusion hepatitis.
intravenous drug user: all new HCV infections
Sexual transmission and transmission from mother to child
have been difficult to document.
most prevalent blood-borne pathogen - U.S.
4 million people in the U.S. (1—2% of the population) are
chronically infected with HCV.
infects hepatocytes: 30-50% of cases progress to chronic
liver diseases
Alcoholism: hepatocellular carcinoma
Cancer: caused by prolonged liver damage and rapid growth
rate of hepatocytes as the cells attempt to regenerate rather
than by a direct oncogenic effect of HCV.
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Liver transplant
Clinical Findings HCV
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acute infection with HCV is milder than infection with
HBV.
Fever, anorexia, nausea, vomiting, and jaundice are
common.
Dark urine, pale feces, and elevated transaminase
levels are seen
Laboratory Diagnosis:
 detecting antibodies to HCV in an ELISA.
 Blood products can now be tested for Ab to HCV.
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HCV Treatment & Prevention:
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Sofosbuvir ( first line)
A combination of alpha interferon and ribavirin is
the treatment of choice for chronic hepatitis C, but it
is expensive and has side effects that can limit its
use.
Patients with chronic HCV infection should be
advised to reduce or eliminate their consumption of
alcoholic beverages to reduce the risk of
hepatocellular carcinoma and cirrhosis
Simeprevir
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HEPATITIS D VIRUS (DELTA VIRUS)
Disease: Hepatitis D virus (HDV) causes hepatitis
D (hepatitis delta).
Important Properties & Replicative Cycle:
 unusual in that it is a defective virus
 cannot replicate by itself because it does not have
the genes for its envelope protein.
 HDV can replicate only in cells also infected
with HBV, because HDV uses the surface antigen
of HBV (HBsAg) as its envelope protein.
 HBV is therefore the helper virus for HDV.
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Transmission & Epidemiology HDV:
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transmitted by the same means as is HBV
sexually, by blood
perinatally.
In the United States, most HDV infections occur
in intravenous drug users who share needles.
HDV infections occur worldwide with a similar
distribution to that of HBV infections.
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HDV Pathogenesis & Immunity:
 the pathogenesis of hepatitis caused by HDV and HBV
is the same
 the virus-infected hepatocytes are damaged by
cytotoxic T cells.
 There is some evidence that delta antigen is
cytopathic for hepatocytes.
 IgG antibody against delta antigen is not detected for
long periods after infection
 uncertain whether long term immunity to HDV exists.
 Because HDV can replicate only in cells also infected
with HBV, hepatitis delta can occur only in a person
infected with HBV.
 A person can either be infected with both HDV and
HBV at the same time, ie, be “coinfected,” or be
previously infected with HBV and then be infected
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with HDV.
HDV
Laboratory Diagnosis:
 detecting either delta antigen or IgM antibody
to delta antigen in the patient’s serum.
Treatment:
 Alpha interferon can mitigate some of the
effects of the chronic hepatitis caused by
HDV but does not eradicate the chronic
carrier state
Prevention of HBV infection:
 Vaccine
 hyperimmune globulin
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HEPATITIS E VIRUS
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major cause of enterically transmitted hepatitis.
common cause of water-borne epidemics of hepatitis
in Asia, Africa, India, and Mexico
uncommon in the United States.
nonenveloped, single-stranded RNA virus tentatively
classified as a member of the calicivirus family.
Clinically the disease resembles hepatitis A, with
the exception of a high mortality rate in pregnant
women.
Pregnant women who acquire HEV have a 20%
fatality rate (compared to 0.5% for the rest of the
population).
India, a country where HEV is endemic.
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HEPATITIS G VIRUS
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member of the flavivirus family, as is HCV.
unlike HCV, which is clearly the cause of both
acute hepatitis and chronic active hepatitis and
predisposes to hepatocellular carcinoma, HGV
has not been documented to cause any of these
clinical findings.
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 EVERY
TIME YOU TAKE
2 STEPS FORWARD YOU
HAVE SUCCEEDED IN
ELIMINATING FAILURE
AND
BACKWARDNESS….

DRS
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