Hepatitis Viruses by dffhrtcv3

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									                 Viral Hepatitis

             Hugh B. Fackrell

Filename: Hepatite.ppt




                                   4/25/2013
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           Hepatitis Virus Outline

    Definitions
    Classification
    Structure
    Multiplication
    Clinical manifestations
    Epidemiology
    Diagnosis
    Control                         4/25/2013
2                Baron’s Web Site
                     Hepatitis

    an ancient disease, the etiology has only
     recently (50 yrs.) been revealed.




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                          Hepatitis

An inflammatory disease
            of hepatocytes
    necrosis
    mononuclear response destroys liver architecture

Liver excretion of bile pigments such as bilirubin
 into the intestine is interrupted




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                      Bilirubin

    Bilirubin: greenish-yellow pigment
     accumulates in the blood and tissues
    Jaundice -
         yellow tinge in the skin and eyes
      caused    by bilirubin


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                 Types of Jaundice

    Pre hepatic: Hemolytic Jaundice
      normal    feces, anemia, reticulocytes
    Hepatic: Hepatocellular Jaundice
        fecal fat, bilirubinuria, Alkaline phosphatase
        high, gamma globulins high
    Post Hepatic: Obstructive Jaundice
      fecal   fat, bilirubinuria, alkaline phosphatase
        high
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          Jaundice of the Newborn

    Premature infants
    bilirubin increases from birth
    peaks at one week
    caused by
      1:excessivehemolysis
      2:immature liver function



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             Hepatitis symptoms

    Swelling and
     tenderness of liver
    Jaundice -yellow
     tinge in the skin and
     eyes
    dark urine
    transaminase, alkaline
     phosphatase levels
                                  4/25/2013
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                 Viral Hepatitis

    Liver infection caused by several
     UNRELATED VIRUSES
    Inflammation and necrosis of the liver
    50% of HAV & HBV are subclincal




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                  Hepatitis types

     Hepatitis A - HAV "infectious hepatitis"
     Hepatitis B - HBV "serum hepatitis"
     Hepatitis C - HCV non A, non B
     Hepatitis D - HDV Delta virus
     Hepatitis E - HEV similar to type “A”



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       Hepatitis A

     “Infectious hepatitis”
     “Epidemic hepatitis”
             HAV

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                   Hepatitis A
             Clinical manifestations
     asymptotic or anicteric in children
     3-5 week incubation period
     liver inflammation
     malaise - flu like symptoms
     self limiting
     low mortality

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                   Hepatitis A
                    Structure
     Picornavirus
     Only one serotype
     Enterovirus type 72
     27-29 nm icosahedral
      ssRNA



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                    Hepatitis A
                   Host Defenses
      antibodies develop late in incubation period
     IgM
       within  a week of dark urine
       peaks a week later
       lasts 40-60 days

     IgG
       after IgM
       peaks 60-80 days
                                             4/25/2013
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                       Hepatitis A
                      Epidemiology
     Global distribution- underreported
     Fecal-oral route,
       person     to person
          water
     Overcrowding & poor sanitation
      Infected food handlers common vector


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         Annual Incidence Viral food
               borne diseases
     Norwalk-like viruses Total Viral food borne
        23,000,000         30,883,391
      Rotavirus           Total Microbial food
        3,900,000          borne incidence
                                 38,629,64
     Astrovirus
          3,900,000
     Hepatitis A
       83,391                CDC

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                       Hepatitis A
                       Diagnosis
     Clinical manifestions
      Viral antigens
       Immunoelectron    microscopy
       RIA
       ELISA
       Immune     Adherence hemagglutination (old
         method)
     Viral antibodies
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                       Hepatitis A
                        Control
      No specific control
     Improve hygiene and sanitation
     Human immunoglobulin
       2   IU anti Hepatitis A /kg body weight
     HAV vaccines in clinical field trials



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     Hepatitis B

     “Serum hepatitis”
          HBV


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                 Hepatitis B
           Clinical Manifestations
     typical viral hepatitis symptoms
     4-26 week incubation period
     more severe than HAV
     CHRONIC PERSISTENT HEPATITIS
     CHRONIC ACTIVE HEPATITIS



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                    Hepatitis B
                     Structure
      Hepadnavirus
      dsDNA, circular, 3200 nucleotides
     enveloped icosahedral virus
     42 nm




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                 Australia antigen
                 “Dane particle”
     small pelomorphic particles 20-22nm
     tubular forms
     excess viral capsids released into blood
      stream




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     3 forms of HBV




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     Dane Particles




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                     Hepatitis B
                    Host Defenses
     Cell mediated Immunity
                for recover in acute phase
       important
       autoimmune liver damage in chronic infections

     Humoral Immunity
          always protective
       not
       HBsAg for Vaccines

     Interferon
       notdetected during infection
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       exogenous application effective
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                    Hepatitis B
                   Epidemiology
     Parenterally ie via blood, saliva, menstrual
      and vaginal discharges, semen and breast
      milk
     infected blood and blood products
     sexual contact
     perinatally from mother to child


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                      Hepatitis B
                      Prevalence
      AREA               HBsAg      anti HBsAg
     Western Europe    0.2-0.5%     4-6%
      USA
     Eastern Europe     2-7 %       20-55%
      USSR
     China              8-20 %      70-95%
      Asia
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                  Hepatitis B
                  Diagnosis
     Electron microscopy
     Viral DNA polymerase
     Viral DNA probes
     Serology




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                         Hepatitis B
                          Serology
     Hepatitis B surface antigen- HBsAg
          10 subtypes
     Hepatitis B core antigen- HBsCAg
     Soluble core associated antigen HBeAg
        Corresponding antibodies to
              each antigen occur


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                      Hepatitis B
                       Control
     No specific control
     Passive Immunization
        HBV immunoglobulin
       250-500 IU within 48 hours
       neonates of infected mothers -immediately after
        birth
     Active Immunization
       HBsAg
       recombinant   DNA in yeast              4/25/2013
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                HBV & Cancer

1. Transformation of the cell by virus
2. Helper virus if the transforming virus is
  defective
3. Co-carcinogen, chemical, cigarette smoke




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               Transformed cells

     lose contact inhibition
     continue to divide
     form random aggregations
     can become invasive
     Not warts: Papovavirus



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     Primary Hepatocellular Carcinoma

     Highest incidence:
       Central  Africa
       Southeast China
       Pacific Islands, Borneo, Sarawak, Taiwan

     Icteric symptoms:
       jaundice,   dark urine, pale stools
      Global 250,000- 1,000,000 deaths /year
      U.S.A. 5000 deaths / year
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                   Acute HBV & Cancer

                           Acute Hepatitis B
              90%                                         1%
                                     Resolution
       Fulminant Hepatitis
     Resolution                                   Chronic Active
                  Asymptomatic                     Hepatitis
                  Carrier            Chronic
                                                    Cirrhosis
           50%
                                                  Hepatic
                                 Extrahepatic     Cell Carcinoma
                                 Disease
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     Hepatitis C

         HCV
     Non -A Non-B


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                  Hepatitis C
            Clinical Manifestations
     resembles HBV
     persistent carrier state
     50% of patients have chronic liver damage
     associated with hepatocellular carcinoma




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               Hepatitis C
     is probably caused by several
            different viruses



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                   Hepatitis C
                  Epidemiology
      in USA causes 90% of post transfusion
      hepatitis
     Mother to infant transmission




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                    Hepatitis C
                    Diagnosis
     C100-3 recombinant viral antigen
     anti c100-3 marker of chronic infection




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                          Hepatitis A               Hepatitis B            Hepatitis C
                            HAV                       HBV                    HCV

        Structure             RNA                        DNA                   HBV

 Cultured in cells             yes                        no                    no


   Epidemiology       endemic & epidemic               endemic               endemic

                           oral/fecal,              blood/serum,            blood/serum,
   Transmission                                     close contact         intimate contact
                          water & food

Incubation period          2-7 weeks                 1-6 months             2-8 weeks

       Symptoms      fever, G-I tract disorder   fever, rash, arthritis   similar to HBV

        Jaundice          1 case in 10                 common                common

           Onset           acute/short             gradual/chronic         acute/chronic

         Vaccine          not available                   yes              not available

 Diagnostic tests              yes                        yes                   yes
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     Hepatitis D

        HDV




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                    Hepatitis D

     Dependovirus, it is defective and cannot
      produce infection unless the cell is also
      infected with HBV.
     Viroid - a naked strand of RNA that enters
      the cell in piggy-back fashion.



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                  Hepatitis D
            Clinical Manifestations
     Dual infection is more severe than HBV
     fulminating hepatitis
     severe rapidly progressive hepatitis
     severe exacerbations




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                   Hepatitis D
                    Structure
     35-37 nm virus particle
     shares coat protein of HBV
      small RNA genome
     one serotype




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                   Hepatitis D
                  Epidemiology
      hemophiliacs and IV drug users
     Contaminated blood and blood products




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     Geographic distribution of HDV




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                      Hepatitis D
                      Diagnosis
     Clinical manifestations
      Delta antigen
       Immunofluorescence
       RIA
       ELISA

     Anti delta antigen
       same   as above

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     Hepatitis E Virus




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                    Hepatitis E

     fecal/oral route
     predominantly found in developing
      countries but is world wide.
     symptoms similar to HAV but mortality 1-
      2% (ten times that of Hepatitis A).
     epidemics - India, Pakistan, Nepal, Burma,
      North Africa and Mexico.
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