Lecture 11: Virology -Hepatitis Viridae Flashcards

1) Viral hepatitis and liver enzyme elevation 2) Epidemiology, serology, and treatment of Hepatitis A virus 3) Transmission, pathogenesis, serology, and treatment of Hepatitis B virus 4) Transmission, manifestations, diagnosis, and treatment of Hepatitis C virus 5) Hepatitis D, E, and G viruses

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1
Q

Viral Hepatitis

A

Infection of liver hepatocytes by viruses

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2
Q

5 RNA Hepatitis Viruses

A
Hep A (HAV)
Hep C (HCV)
Hep D (HDV)
Hep E (HEV)
Hep G (HGV)
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3
Q

1 DNA Hepatitis Virus

A

Hep B (HBV)

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4
Q

Acute Viral Hepatitis

  • what?
  • ________ incubation period
  • symptoms
  • enzymes produced
A

sudden illness with a mild to severe course followed by complete resolution

  • variable incubation period
  • flu like symptoms
  • 1-2 wks later patient develops jaundice
  • necrosis of hepatocytes produces enzymes aspartate aminotransferase (AST), alanine aminotransferase, gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase
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5
Q

Chronic Viral Hepatitis

  • what?
  • which strains?
  • why is diagnosis difficult?
A

prolonged course of active disease or silent asymptomatic infection

  • HBV, HCV, & HDV can cause chronic hep
  • diagnosis difficult due to patient being asymptomatic with only an enlarged tender liver and mildly elevated liver function enzyme levels
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6
Q

Hepatocytes produce ____ and ____. The cells that line the bile canaliculi produce _______________ and ______.

A

AST; ALT

alkaline phosphatase; GGT

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7
Q

Cell necrosis results in release of ___ and ____

A

AST; ALT

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8
Q

Initially there is high ___ and ____ & little elevation in _____________ and _____

A

AST; ALT

alkaline phosphatase; GGT

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9
Q

As infection worsens, the liver ____ and the canaliculi _________, resulting in a backup of ____________ in the blood

A

swells; narrows; bilirubin

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10
Q

Hepatitis A Virus

  • structure
  • family?
  • transmission
A

-naked icosahedral capsid with (+) ssRNA nucleic acid
family picornaviridae
-transmitted by fecal-oral route

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11
Q

Hepatits A Virus

-Epidemiology

A
  • 6000 cases reported each year in the US
  • Poor hand washing, persons ingesting fecally contaminated drinking water, close person-to-person contact in institutions such as day care
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12
Q

Hepatitis A Virus

  • Serology
  • > what part is antigenic?
  • > which immuniglobulins?
  • > active vs old infection
A
  • HAV capsid is antigenic; host production of anti HAV IgM and later anti-HAV IgG
  • Patient with active infection has anti-HAV IgM detectable in the serum
  • Anti-HAV IgG indicates old infection, no active disease
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13
Q

Hepatitis A Virus

-Treatment

A
  • inactivated Hepatitis A vaccine recommended for high risk adults
  • once exposed, pooled immune serum globulin will prevent or decrease the severity of infection, if given early
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14
Q

Hepatits B Virus

  • Structure
  • > family
  • > size
  • > genome
  • intact virus is called what? and is composed of?
A
  • Hepadnavirus
  • HBV= BIG and BAD
  • Big virus (42 nm) with an enveloped icosahedral capsid and circular dsDNA
  • intact virus is callled Dane particle composed of an envelope and capsid studded with protein spikes
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15
Q

Hepatitis B Virus

-Viral Proteins

A

4 viral proteins encoded by viral DNA:

1) Capsid protein (hep B capsid antigen) [HBcAg]
2) Envelope protein (hep B surface antigen) [HBsAg] -anti-HBsAg are protective
3) Multifunctional reverse transcriptase/DNA polymerase
4) Nonstructural regulatory protein, X protein

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16
Q

Hepatitis B Virus

  • Transmission
  • > found where?
  • > titer amount as high as?
  • > soluble component of the core is? serves as what?
  • > pregnant mothers
A
  • found in all human body fluids of an infected patient and serves as a source of infection
  • titer of virus in acute infection is as high as 10^8 virus particles /ml
  • during active infection, a soluble component of the core is released called HBeAg, a marker for active disease and a highly infectious state
  • pregnant mothers with HBeAg in their blood have a 90% transmission rate to offspring
17
Q

Hepatitis B Virus

-Pathogenesis

A

Causes both acute and chronic hepatitis. Disease states caused by HBV:

  • Acute hepatitis
  • Fulminant hepatitis -severe acute hepatitis with rapid destruction of the liver
  • Chronic hepatitis: (see next notecard)
18
Q

Hepatits B Virus
Pathogenesis
->Chronic Hepatits

A
  • Asymptomatic carrier -never develops antibodies against HBsAg (anti-HBsAg)
  • > Chronic-persistent hepatitis: low grade “smoldering” hepatits
  • > chronic active hepatitis: acute hepatits continuing without normal recovery (lasts longer than 6-12 months
  • > co-infection with hepatitis delta virus (HDV)
  • liver injury is due to cell-mediated immune response
  • HLA-I-restricted cytotoxic T cells, react specifically with HBcAg and HBeAg expressed on surface of infected hepatocytes
  • immune complexes of antibody and HBsAg can deposit in tissues and activate immune system resulting in arthritis, skin, and kidney damage
19
Q

What is an indication that an HBV infection has become chronic?

A

the continued presence of HBsAg beyond 6 months and the absence of anti-HBs

20
Q

Hepatitis B Virus
-Serology

(see slide 18)

A

HBsAg -indicates live virus and infection
->HBsAg = Disease
->Anti-HBsAg = Immune, Cure, No active disease
HBcAg -antibodies to HBcAg are not protective
->IgM anti-HBcAg = New infection
->IgG anti-HBcAg = Old infection
HBeAg -indicates high infectivity and active disease
->HBeAg = High infectivity
->anti-HBeAg = Low infectivity

21
Q

The currently used vaccine, containing recombinant hepatitis surface antigen, elicits only ___________ antibody, which is the __________ antibody.

A

anti-HBsAg; neutralizing

22
Q

Hepatitis B Virus

-Treatment

A
  • Active Immunization
  • Anti-viral agents:
    • > Interferons (IFN-alpha) suppress HBV DNA levels and leads to seroconversion of HBeAg in around 35% of chronic HBV patients
    • > Nucleoside analogs (lamivudine, adefovir, entacavir) Drug resistance, need for long-term treatment and expense are drawbacks
23
Q

Hepatitis C Virus

A
  • Emerging disease publicized in mid 90’s
  • Originally termed “non A, non-B” hepatitis
  • Leading cause of chronic hepatitis, 1.5% Americans seropositive for HCV
  • 85% of those with exposure and acute infection develop chronic hepatitis
24
Q

Hepatitis C Virus

-Transmission

A

transmitted parenterally, with primary means being injection drug use

25
Q

Hepatitis C Virus

-Manifestations

A
  • Incubation period is 6-12 weeks

- Acute infection is usually asymptomatic

26
Q

Hepatitis C Virus

-Diagnosis

A
  • diagnosed by testing for anti-HCV antibodies detectable within 6-8 weeks after exposure
  • a positive test is confirmed by recombinant immunoblot assay (RIBA) or measuring HCV viral RNA
27
Q

Hepatitis C Virus

-Treatment

A

Interferon and ribavarin are FDA licensed drugs for treating chronic HCV

Pegylated interferon-alpha plus ribavarin is drug of choice

28
Q

Hepatitis Delta Virus

A
  • RNA virus transmitted parenterally; can only replicate with the help of HBV
  • The helical nucleocapsid uses HBV’s envelope HBsAg

HBV + HDV = BIG BAD DUDE

29
Q

Hepatitis Delta Virus

-Co-infection

A
  • HBV and HDV are both transmitted together parenterally and cause acute hepatitis
  • antibodies to HBsAg is protective against both HBV and HDV
30
Q

Hepatitis Delta Virus

-Superinfection

A
  • HDV infects a person who has chronic HBV infection (like HBV carriers) resulting in acute hepatitis in a patient already chronically infected with HBV
    • > Superinfection is severe with higher incidence of fulminant hepatitis, cirrhosis and greater mortality (5-15%)
    • > Patients with chronic HBV cannot make anti-HBsAg and so remains chronically infected with both HBV and HDV
  • Diagnosis is by the detection of delta antigen and antibodies to delta antigen
31
Q

Hepatitis E Virus

  • aka?
  • transferred how?
  • what does “E” stand for?
A
  • HEV is often referred as “non-A hepatitis” as it shares similarities with HAV
  • transferred by fecal-oral route
  • “E” stands for Enteric. Endemic to Asia, India, Africa, and Central America
32
Q

Hepatitis G Virus

  • RNA or DNA?
  • family?
  • transmission?
A
  • RNA virus in the Flavivirus family
  • Transmitted by transfusion & parenternal routes
  • Not conclusively shown to cause liver disease