Animated hierarchy and process graphics

with SmartArt
Reproducti
Printing Removing
1 on
instruction 2 instruction
s
3 instruction
s
For yoursreference, the To print the If you notice delays in
steps required to reproduction slide effects or a
reproduce each of these instructions in this file: decrease in
slides have been 1.Select the slide that performance, you may
included in the Slide you want to reproduce. want to remove the
Notes. 2.Place your cursor in reproduction
the Slide Notes. instructions in the Slide
3.Press CTRL + A, and Notes. To remove the
then Copy the text. instructions from a
4.Open a new document particular slide:
in Microsoft Word.
5.Then Paste the text 1.Place your cursor in
into the Word the Slide Notes.
document. 2.Press CTRL + A, and
6.Print the Word then press DELETE.
document.
Hepatitis Viruses
Antibodies
-Kiran Govindankutty
 Hepatitis Viruses:
Introduction
• five medically important viruses are
commonly described as "hepatitis
viruses" because their main site of
infection is the liver.
Hepatitis A virus (HAV)
Hepatitis B virus (HBV)
Hepatitis C virus (HCV)
Hepatitis D virus (HDV, delta virus) and
Hepatitis E virus (HEV)
 Clinical Features of Hepatitis
Virus Mode of
Viruses.
Chronic Laboratory Vaccine Immune
Transmission Carriers Test Available Globulins
Usually Useful
Used for
Diagnosis

HAV fecal–oral No IgM HAV Yes Yes

HBV Blood, sexual, Yes HBsAg, Yes Yes

at birth HBsAb,
IgM HBcAb

HCV Blood, sexual? Yes HCV Ab No No

HDV Blood, sexual? Yes Ab to No No

delta Ag
HEV fecal–oral No None No No
 HEPATITIS A VIRUS
• transmitted by the fecal–oral route.
• humans are the reservoir for HAV.
• virus appears in the feces ~ 2 weeks before
the appearance of symptoms, so quarantine
is ineffective.
• children are the most frequently
infected group
• unlike HBV, HAV is rarely transmitted via
the blood, because the level of viremia is
low and chronic infection does not occur.
Pathogenesis & Immunity

• The virus probably replicates in

the gastrointestinal tract and
spreads to the liver via the blood.
• Immune response is initially of IgM
antibody.1–3 weeks later
production of IgG antibody
provides lifelong protection.
 Laboratory Features
Hep.A Virus
• abnormal liver function tests: ↑
aminotransferases and bilirubin,
supplement the clinical findings
• Virus detected in
the liver
stool
bile
and blood
by
immunoassays
nucleic acid hybridization assays, or PCR.
 HAV ANTIBODIES

• Anti-HAV IgM appears

during the acute phase( peaking about 2 weeks
after elevation of liver enzymes)
declines to non-detectable levels within 3–6
months.
• Anti-HAV IgG appears soon after the onset of
disease and persists for decades.
• Thus, detection of IgM-specific anti-HAV in the
blood of an acutely infected patient confirms the
diagnosis of hepatitis A.
Immunologic and biologic events associated with HAV infection
.
 HEPATITIS B VIRUS
(hepadnavirus family)

• an enveloped virion
• a partially double-stranded circular
DNA genome
• envelope contains the protein
surface antigen (HBsAg), which is
important for laboratory diagnosis
and immunization.
 Clinical Findings

Acute infection
– general ill-health, loss of appetite, nausea, vomiting, body
aches, mild fever, itchy skin, jaundice.
– more severe liver disease (fulminant hepatic failure)
– The infection may be entirely asymptomatic and may go
unrecognized.
Chronic infection
– asymptomatic or with a chronic inflammation of the liver,
leading to cirrhosis
– increases the incidence of hepatocellular carcinoma,has
been linked to the development of
Membranous glomerulonephritis
 Lab Diagnosis(HBV)
HBV antigens and
antibodies
detected 1 week after infection.
T HBV PCR used to confirms the
presence of HBV/ measure viral
I load for viral mutants that do not
produce the "e" and/or normal
M surface antigens
Hepatitis B DNA
E
(HBV DNA) detected soon after initial
L infection by hepatitis B at about
the same time as HBV DNA..
I HB DNA Tests for HBV DNA generally
polymerase(HBV DNAp) used as indicators of disease
N progression, suitability for
therapy and research purposes
E

ANTIGENS ANTIBODIES
 HBV Antigens

Antigens

HBx
HBcAg thought to play
not detectable a role in
in blood HBsAg HBeAg development of
HBV-related
Detected in
liver cells Hepatocellular
Carcinoma
Hepatitis B surface Antigen
(HBsAg)
• HBsAg appears during incubation period -detectable in most patients
during the prodrome and acute disease.
• marker of acute and chronic infection.
• Persistence for > 6months signifies chronic infection.
• Disappearance of HBsAg followed by the appearance of HBsAb is the
hallmark of recovery.
• Window period = short period of time during which HBsAg becomes
undetectable, but before the HBsAb is detectable.
• If acute HBV is suspected, an HBcAb IgM is done for diagnosis
• After exposure to HBV, a minority may be positive for both HBsAg and
HBsAb. It is believed that in these cases the HBsAb is not able to
neutralize the HBsAg, and, therefore, the antigen remains detectable
Hepatitis B envelope Antigen
(HBeAg)
• A marker of HBV replication, infectivity and
transmissibility.
• E antigen is secreted from infected cells into
the blood.
• Absence of HBeAg does not always ensure that
there is no HBV replication or infectivity. (The
precore mutant strain of HBV does not produce
HBeAg, but it still successfully replicates and
can cause progressive liver damage).
 HBV Antibodies

Antibodies

HBcAb HBsAb HBeAb

HBcAb IgM HBcAb IgG

 Hepatitis B surface
Antibody (HBsAb)

• HBsAb is the antibody directed against HBsAg.

• Important marker of recovery and of immunization.
• HBsAb is not detectable in the chronic carrier state. HBsAb
is being made but is not detectable in the laboratory tests
because it is bound to the large amount of HBsAg present in
the blood.
• Isolated HBsAb is most commonly the profile seen in
individuals successfully immunized against HBV.
Hepatitis B core Antibody
(HBcAb)

• HBcAb is detectable throughout HBV infection (either IgM or IgG subclass.

• HBcAb is an important marker of natural exposure to the virus
• distinguishes infection from vaccination.
• HBcIgM is usually a marker of more acute infection
• HBcIgG is usually seen during later part of the infection.
• Detectable HBcAb IgM does not always signify acute HBV infection. It may
remain detectable for up to several years after the acute infection and may
increase to detectable levels during exacerbations of chronic HBV.
• After natural infection with HBV, the HBcAb IgG remains detectable whether
the individual recovers or develops chronic infection.
 Isolated HBcAb detected
without
detectable HBsAg or HBsAb
• The explanations may include:
• the window period of acute HBV infection
• years after recovery from HBV infection
• when the titer of HBsAb falls below detectable levels, and after
years of chronic infection
• when the HBsAg levels drop below detectable levels but
without neutralizing antibody (HBsAb) present.
• In cases of isolated HBcAb, there have been cases of positive
HBV DNA and HBV transmission reported.
• The management of an isolated HBcAb case include
– repeat testing of the HBsAb, HBsAg, HBcAb IgM, and IgG.
– It would also be reasonable to check HBV DNA, particularly if chronic
liver disease is suspected.
 Hepatitis B e Antibody
(HBeAb)

• The loss of HBeAg and the appearance of the

HBeAb is called seroconversion.
• When seroconversion occurs, HBV DNA typically
becomes undetectable and there may be remission
in terms of liver disease, although this is not
always the case.
• There have been cases of HBV infection described
in which despite the loss of HBeAg and with the
appearance of HBeAb, there was continued
persistence of HBV DNA with ongoing liver injury.
 ANTIGENS ANTIBODIES
HBcAb IgM
(acute Infection)
HBcAg HBcAb
Detected In liver cells only
HBcAb IgG

marker of
acute and HBsAg HBsAb
chronic Chronic or recovered
infection life long presence

HBeAg HBeAb
marker of recovery and of
immunization

HBx
Protein loss of HBeAg and the appearance of
the HBeAb (seroconversion)
HBV DNA typically becomes undetectable
Remission in terms of liver disease

marker of HBV replication

and infectivity
HEPATITIS B PROFILE

HBsAg
HBeAg
HBcAb IgM
HBcAb Total
HBsAb
HBeAb
 Hepatitis C Virus (HCV)

–RNA virus -6 major genotypes identified

–genetically sequenced in 1989 after which it became possible to test for
HCV.
–transmitted parenterally
–high prevalence among individuals with a history of alcoholism
EXPOSURES ASSOCIATED WITH HEPATITIS C INFECTION
–Transfusion, transplant from infected donor
–Occupational exposure to blood (mostly needle sticks)
–Iatrogenic (unsafe injections)
–Birth to HCV-infected mother, Sex with infected partner (multiple
sex partners)
HOUSEHOLD TRANSMISSION OF HEPATITIS C
–Rare, but not absent
–Could occur through percutaneous/mucosal exposures to blood
eg, IV therapy, injections, razors, toothbrushes.
 CLINICAL PICTURE
Acute Hepatitis C
• In most cases, not identified
• Patients may present with malaise, nausea, vomiting, right upper quadrant pain, and
jaundice.
• Those who do develop symptomatic acute HCV may mount a successful immune response
against the virus and clear the virus without treatment (interferon/ribavirin).
Chronic Hepatitis C
• After exposure to HCV, most individuals will develop a chronic infection with persistent
viremia with no symptoms.
• Symptoms that may be associated- fatigue, nausea, anorexia, myalgia, arthralgia, and
weight loss.
• symptoms are are quite nonspecific; so, other causes must be considered.
• often identified incidentally when an abnormality in the liver tests is noted such as a mild
elevation in the transaminases.
• Chronic HCV may also be detected in patients initially presenting with complications
of cirrhosis such as ascites, variceal bleeding, or encephalopathy in a person previously
unknown to have liver disease. Once an individual is cirrhotic, it is far more likely that
there will be lots of symptoms related to the liver failure.
 Lab Diagnosis

• Diagnostic tests for HCV include serologic tests for antibody and molecular tests to detect
viral proteins (RNA).
Serologic Tests
• Screening assays and Supplemental tests for confirming infection
• The screening assay is a multiantigen enzyme immunoassays (EIA).
– possibility of false positive and negative test results still exists.
– False negative test results may occur in individuals who are immunocompromised (eg, HIV,
hypogammaglobulinemia), and, therefore, may not mount an adequate immunoglobulin response
to be detectable by the assay.
– Factors associated with false positive tests include: low prevalence situations where
– an individual does not have clear risk factors for exposure to HCV or the presence of high
immunoglobulins as with other autoimmune disease.
– If a false positive test is suspected the supplemental assay, the recombinant immunoblot
assay (RIBA) should be used.
• RIBA is performed only on specimens in those cases where a positive EIA result is
called into question as in low risk groups.
• RIBA is not used as the primary screening test (more technically demanding)
• In patients with known risk factors for HCV with a positive screening test for HCV, it is not
necessary to perform a RIBA test—rather, it is more informative to move directly to HCV
RNA quantification and characterization (genotype) with molecular tests.
 Molecular
Tests(HCV)
•based on detecting HCV RNA in serum.
•very important in identifying and quantifying active infection
•monitoring response to antiviral therapy.
•used to assess the viral load or the genotype of the HCV.
•two fundamental types of the viral load molecular tests
– the qualitative tests
– the quantitative tests.
The qualitative tests have a lower threshold of detection of HCV RNA -useful in
confirming evidence of active HCV infection or not. When a qualitative HCV RNA test
is ordered, the result will be either positive or negative.
useful in following patients who have cleared the virus in order to confirm ongoing
clearance with the most sensitive assay possible.
When a quantitative HCV RNA test is ordered, the result will be expressed as an
actual number (viral load)
Molecular tests also allow for identifying the genotype of the virus.
-relevant in cases when patients are considering treatment for their HCV infection
with interferon and ribavirin{Certain genotypes (genotypes 2,3) are significantly
more sensitive to the combination
treatment compared to others (genotypes 1,4), and actually have a shorter course of
treatment with a reduced dosage of ribavirin
HEPATITIS D VIRUS (HDV)

• HDV is a defective RNA virus.

• cannot survive without the HBV, which provides it
with its outer envelope (HBsAg).
• So found only in the setting of concurrent or pre-
existing infection with HBV. HDV does depend on HBV
for its survival, but interestingly, the geographic
distribution of HDV does not exactly parallel that of
HBV.The differences in the geographic distribution
between HDV and HBV have been attributed to
differences in their efficiency of transmission.
• routes of transmission for HDV include sexual,
parenteral, and household.
CLINICAL PICTURE (HDV)

• acquired at the same time as HBV (coinfection) or

• in persons already chronically infected with the HBV (superinfection).
• Coinfection- the clinical picture is identical to that of acute HBV monoinfection.
usually transient and self-limited.
• Superinfection-the clinical picture is that of hepatitis exacerbation in a person
previously known to have HBV or it may be the initial diagnosis of chronic HBV.
Serologic Tests
• include testing for anti-HDV antibodies (IgM and IgG).
• also important to test of other causes of hepatitis especially HBV.
• Testing for HBV will yield information about the phase of HBV infection to try to
figure out whether the current infection represents co-infection or super-
infection. This is important in predicting the clinical course and likelihood of
chronic infection.
The Role of Liver Biopsy
• Tissue markers of HDV infection include hepatitis D antigen (HDAg) and HDV
RNA. intrahepatic HDAg has been proposed as the gold standard for the
diagnosis of current HDV infection.
 HEPATITIS E VIRUS (HEV)

• RNA virus that is enterically transmitted usually in

contaminated water.
• similar to HAV in that both of these viruses are transmitted by
the fecal-oral route.
• HEV typically causes an acute, self-limited hepatitis.
Symptoms similar to that of acute hepatitis
Serologic Tests
– elevation of the transaminases and total bilirubin
– Jaundice often sets in after the peak of the transaminases.
– There are serologic tests to identify antibodies against HEV
and to directly detect HEV antigens, however, these tests are
largely for research purposes
– An important part of making a diagnosis of acute HEV infection
includes excluding the other causes of acute hepatitis
serologically including hepatitis A, B, C, D, as well as
cytomegalovirus (CMV) and Epstein-bar virus (EBV).