Download Pathogenesis of HBV Infections Acute Infection

HEPATITIS VIRUSES
Part 2
Pathogenesis of HBV Infections
• HBV is transmitted only in blood and body fluids
• Replication starts in the hepatocytes, “the only host cells”
• HBsAg particles are liberated into blood stream, “they are
not infective”
• Dane particles “complete virion” are so numerous, up to
1010/ml, 0.001 ml of blood can transmit infection
• Incubation period 50-180 days
• Liver injury may be due to cellular immune response
directed toward the new antigens deposited in the cell
membrane of infected cells
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Pathogenesis of HBV Infections
1. Acute Infection
• Follows initial infection and is characterized by a high
rate of viral replication.
• Damage to liver cells which results in:
• high blood concentration of liver enzymes
• and the obstruction of small bile tubes due to inflammation
leads to the development of jaundice.
• In severe cases liver function may be so damaged that
clotting is impaired or hepatic encephalopathy develops.
This is referred to as acute fulminant hepatitis.
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Pathogenesis of HBV Infections
• Percentage of acute infection that will not be cleared and
become chronic infection:
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Between 1% and 4% of adults,
about 70–80% of infants and children,
and 90% of neonates
40% of hemodialysis patients
and up to 20% of patients with immune deficiencies.
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Pathogenesis of HBV Infections
2. Chronic infections
• Chronic HBV infection is defined as HBV infection
lasting longer than 6 months.
• It includes a spectrum from chronic asymptomatic carrier
state to chronic active hepatitis with rapid progression to
cirrhosis.
a) Chronic persistent (carriers):
• are often asymptomatic and may not be aware that they are
infected;
• they are capable of infecting others
• no anti HBsAg “antibodies”
• “mild degree of liver damage”
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Pathogenesis of HBV Infections
b) Chronic active hepatitis:
• develops in more than 25% of carriers and often results in
cirrhosis
• Significant damage to the liver
• Patients at risk may develop cirrhosis or hepatocellular
carcinoma which arises as a result of integration of viral
genome into the DNA of the hepatocytes.
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Laboratory Diagnosis
• HBV infection cannot be differentiated on the basis of
clinical symptoms alone, and definitive diagnosis depends
on the results of serologic testing
• Serologic markers of HBV infection vary depending on
whether the infection is acute or chronic.
• Liver function tests, abnormally elevated “transaminases,
bilirubin, alkaline phosphatase, LDH”
• The presence of HBsAg confirms diagnosis, tested by
ELISA, PCR, RIA
• Liver biopsy
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Laboratory Diagnosis
• HBsAg is the most commonly used test for diagnosing
acute HBV infections or detecting carriers.
• HBsAg can be detected as early as 1 or 2 weeks and as
late as 11 or 12 weeks after exposure to HBV when
sensitive assays are used.
• The presence of HBsAg indicates that a person is
infectious, regardless of whether the infection is acute or
chronic.
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Laboratory Diagnosis
1. May be recovering from acute HBV infection
2. May be distantly immune and the test is not sensitive
enough to detect a very low level of anti-HBs in serum
3. May be susceptible with a false positive anti-HBc
4. May be chronically infected and have an undetectable
level of HBsAg present in the serum
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Control of HBV Infections
• Blocking of person-to-person transmission, prevent blood or
body fluids of infected persons gaining access to the
circulation of
someone else.
• Active immunization with HBsAg obtained by recombinant
DNA technology (in yeast) for high-risk groups and infants
or plasma derived vaccine.
• Passive immunization: Human immunoglobulin with a high
titer of anti-HBs (HBIg: hepatitis B immunoglobulin), which
gives immediate passive protection, should be given with
active vaccine.
• HBIg is given for healthcare staff who suffer “needle-stick”.
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Treatment
• Two major groups of antiviral treatment have been
licensed for the treatment of chronic HBV infection in
many countries.
• These include interferon alpha (IFNa, or PEG-IFNa)
and nucleoside or nucleotide analogues such as
lamivudine.
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Hepatitis C
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It belongs to Flaviviridae family genus hepacivirus
HCV diameter is 50 nm
Icosahedral symmetry, Enveloped
Positive single stranded RNA
There are 6 major genotypes (1-6)
HCV has 2 envelope glycoproteins; E1 and E2,
two transmembrane proteins; NS1 and NS2 in addition to RNA
polymerase (NS5B) and interferon resistance protein(NS5A)
• HCV has a high mutation rate
• HCV has high rate of replication, one trillion particles per day
• Transmission is similar to HBV
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Epidemiology
• Incubation period: 2-26 weeks
• An estimated 170 million people are infected worldwide with HCV.
• About 2-3 million people are infected per year
• Co-infection with HIV is common
• HCV is considered to be the most common cause of
post- transfusion hepatitis.
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Pathogenesis
1. Acute hepatitis C
• It refers to the first 6 months after infection with HCV.
• Between 60-70% of infected people develop no symptoms
during the acute phase.
• Symptoms include decreased appetite, fatigue, abdominal pain,
jaundice and itching.
• HCV is detected in blood within 1-3 weeks after infection
using PCR technique.
• Antibodies are detectable within 3-15 weeks.
• Viral clearance rates are highly variable, 10-60% of infected
persons clear the virus during the acute phase as shown by
normal liver enzymes.
• Most patients develop chronic infection lasting more than 6
months
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Pathogenesis
2. Chronic hepatitis C
• It is often asymptomatic.
• One third of patients progress to liver cirrhosis in less than 20
years, others may develop liver cancer.
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Treatment
• IFN-α-2a injection
• Ribavirin tablets (a purine nucleoside analogue), it inhibits viral RNA
polymerase, it may cause shift of TH2 into TH1.
• Treatment may last for 24-48 weeks depending on HCV genotype.
• Vaccination against HAV and HBV is strongly recommended, as
infection with a second virus could worsen their liver disease.
• No vaccine against HCV is available.
• Alcoholic beverages consumption accelerates HCV associated cirrhosis
and makes liver cancer more likely.
• Smoking may have the same effect.
• Amantadine may be effective in combination with IFN-α and Ribavirin.
• HCV resistant strains develop against IFN-α and/or Ribavirin
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Laboratory Diagnosis
• Liver enzymes increased (ALT in particular)
• PCR
• Used to diagnose HCV in the acute phase
• To monitor the response to antiviral therapy
• Anti HCV antibodies
• Genotyping is recommended to determine the length
and potential response to IFN-α.
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Delta Agent (HDV)
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Incomplete RNA virus
HBV-dependent “for replication”
It may be transmitted along with HBV
May be detected in hepatocyte nuclei of patients with
chronic HBV infection
• Its outer coat is formed from HBsAg
• It uses HBV S antigen to provide the protein for its envelope
and thus HDV can only replicate and spread within HBVinfected individuals.
• Recovery is usually complete and development of chronic
hepatitis D is rare (less than 5% of acute hepatitis).
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Laboratory Diagnosis
• Diagnosis of the active infection depends on detecting
the delta antigen or its IgM antibody in the blood
• Immunization against HBV also protects against
infection with delta agent
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Hepatitis E Virus “HEV”
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RNA(+), single stranded.
Icosahedral symmetry, nonenveloped.
Size: 27-34 nm.
HEV has one serotype and 4 genotypes.
• Genotypes 1 and 2 are restricted to humans.
• Genotypes 3 and 4 infect humans, pigs and other animal species.
• In addition an avian virus has been described which causes hepatitisspleenomegaly syndrome in chickens.
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Spread via fecal-oral route
Clinically, it is comparable to HAV.
HEV causes severe infection in pregnant women.
Incubation-period 2-7 weeks
A vaccine has been developed recently which is based on recombinant
viral proteins, (registered in China).
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Laboratory Diagnosis
• Definitive diagnosis of hepatitis E infection is usually
based on the detection of specific IgM antibodies to the
virus in a person’s blood; this is usually adequate in
areas where disease is common.
• Additional tests include reverse transcriptase
polymerase chain reaction (RT-PCR) to detect the
hepatitis E virus RNA in blood and/or stool.
• This test is particularly needed in areas where hepatitis E is
infrequent, and in cases with chronic HEV infection.
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