Infectious Causes of Hepatitis Flashcards

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1
Q

acute viral hepatitis presents with

A
  • non-specific flu like symptoms
  • jaundice
  • dark urine
  • pale faeces
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2
Q

chronic viral hepatitis presents as

A
  • general malaise
  • cirrhosis, liver cancer
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3
Q

early exposure to acute viral hepatitis (HAV, HEV) results in

A
  • less severe acute disease (not mounting as strong an immune response)
  • higher rates of chronic infection
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4
Q

Hep A belongs to what family of viruses?

A

Picornaviridae (polio, rhinoviruses)

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5
Q

What is the structure of HAV?

A
  • non-enveloped - resistant to stomach acid, dessication, outside environements
  • +ssRNA
  • 30nm, 7500nt encode single polyprotein
  • single serotype worldwide
  • replicates in cell culture tf able to produce vaccines
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6
Q

What is the HAV (+HEV) life cycle?

A
  • transmitted from bile or faeces into food/water
  • ingested
  • replicates in intestinal epithelia
  • travels through blood to liver
  • replicates in liver
  • gets into bile and faeces
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7
Q

ALT indicates

A

presence of replicating virus

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8
Q

How is acute viral hepatitis diagnosed?

A
  • determine acute vs chronic/past
  • serological tests (ELISA)
    • IgM Ab to viral proteins (acute)
      • reactive 1-2wks post-infection
    • IgG Ab to viral proteins (convalescent)
      • rising titre confirms acute
  • NA tests (PCR) on blood/faeces (not as helpful with timing infection)
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9
Q

What is the incubation period of HAV?

A
  • Average: 30 days
  • Range: 15-50 days
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10
Q

HEV belongs to which family?

A
  • Hepeviridae
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11
Q

What is the structure of HEV?

A
  • non-enveloped but more fragile than HAV (doesn’t survie environment as well)
  • icosahedral
  • 30nm (small, similar to HAV)
  • +ssRNA (like HAV)
  • 7.7kb (similar size to HAV)
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12
Q

What is the incubation period of HEV?

A
  • Average: 40 days
  • Range: 2-10 weeks
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13
Q

How is HEV diagnosed?

A
  • serology - ELISA for IgM and IgG
  • NA assays (PCR) of serum and faeces
  • Immune EM
  • recently cutltured in vitro - candidate for vaccines
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14
Q

Which hepatitis virus has the highest risk of perinatal transmission?

A

HBV 30-50%

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15
Q

What is the structure of HBV?

A
  • double-walled:
    • outer envelope
    • inner capsid
  • also exists as incomplete envelope-only particles that are non-infectious
    • HBsAg only
  • dsDNA with an incomplete segment
  • carries DNApol and RNA primer
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16
Q

How does HBV replicate?

A
  • infects predominantly hepatocytes
  • core enters nucleus and the ssDNA gap is ‘repaired’
  • forms covalently closed circular DNA episome
  • cccDNA acts as template for pregenome RNA
    • encodes core, precore proteins and polymerase
  • pregenome RNA form an encapsulated structure with polymerase
  • reverse transcribed into DNA forming a new core particle
  • DNA core particle can re-enter nucleus to amplify copies of ccDNA or assemble surface proteins via RER-golgi and bud off to infect
17
Q

What is the life cycle of HBV (and HDV and HVC)?

A
  • transmitted by blood, semen, exudates, secretions
    • sex, close contact, or injection
  • penetrates mucosal epithelia
  • finds its way into blood
  • replicates in hepatocytes of liver
18
Q

How is HBV transmitted?

A
  • perinatally by HBeAg positive in high prevalence populations
  • sexual transmission - sex workers, homosexuals
  • parenteral - IVDA, health workers
19
Q

What is the incubation period of HBV?

A
  • Average: 60-90 days
  • Range: 45-180 days
20
Q

infection with HBV at <5 years results in

A
  • fewer acute symptoms - jaundice in less than 10%
  • higher rates of chronic infection - 30-90%
21
Q

What are the HBV sequelae?

A
  • chronic carrier (HBsAg+)
  • immune mediated liver damage
  • cirrhosis
  • liver failure
  • primary hepatocellular carcinoma
    • most common cause of liver cancer
22
Q

What are the diagnostic markers used in HBV?

A
  • HBsAg - general marker of infection
  • anti-HBs Ig - recovery, immunity, or vaccination
  • anti-HBc IgM - acute infection (rising titre)
  • anti-HBc IgG - past or chronic infection
  • HBeAg - active replication
  • anti-HBe Ig - no longer replicating but can be sAg +ve from integrated HBV
  • HBV-cccDNA - active replication
23
Q

What are the current HBV antivirals?

A
  • pegylated IFN-a
  • nucleoside and nucleotide analogues
    • lamivudine, entecavir
    • adefovir, tenofovir
24
Q

How does HDV infect?

A
  • co-infection with HBV
    • HBV provides sAg protein, in which HDV resides
    • sAg allows HDV passage into hepatoctes
25
Q

What is the structure of HDV?

A
  • within HBsAg
  • 70% self-complimentary ssRNA (viroid)
  • produces delta antigen (core of viral particle)
26
Q

What are the clinical features of HBV-HDV coinfection?

A
  • severe acute disease
  • low risk of chronic infection
  • this is opposite to superinfection, where HBV infects first, then HDV
27
Q

What are the clinical features of HBV-HDV superinfection?

A
  • superinfection = HBV first, then HDV
  • develop chronic HDV infection
  • high risk of sever chronic liver disease
28
Q

What family does HCV belong to?

A

Flavivirus

29
Q

What is the structure of HCV?

A
  • ss linear +RNA genome in nucleocapsid core
  • high mutation rate and genotype diversity
    • Aus: 3a, 1a, 1b, 2
  • enveloped - E1 and E2 glycoproteins
  • forms a polyprotein that is cleaved by non-structural protease
30
Q

How does HCV replicate?

A
  • associates with lipid and enters hepatocytes via lipid receptors or ones that interact with the envelope proteins
  • enters via endosome, uncoated –> release RNA
  • RNA targets ER where its translated
  • produces -ssRNA to increase +ssRNA and tf proteins
  • highly error-prone = mutations
  • viruses leave via excocytosed vesicles into blood
    • can be cell-cell transmission between hepatocytes
31
Q

Telapravir and Boceprevir target

A

NS3, the protease that cleaves the HCV polyprotein

32
Q

What is the incubation period of HCV?

A
  • Average: 6-7 weeks
  • Range: 2-26 weeks
33
Q

What are the clinical features of HCV?

A
  • jaundice is less common (30-40%)
  • 70% risk of chronic hepatitis
  • 70-90% risk of persistent infection
  • no protective Ab response is detected
    • tf vaccines difficult
34
Q

What are the HCV sequelae?

A
  • 70-90% become chronic carriers
  • liver fibrosis, cirrhosis, and failure
  • primary HCC, often in conjunction w/HBV
  • 170-300m carriers
  • 5% lifetime mortality
35
Q

What antivirals are used in HCV?

A

early (effectiveness dependent on IL28B gene):

  • pegylated IFN-a (significant side effects ie fever)
  • ribavirin (nucleoside inhibitor, not v effective)

new:

  • direct acting antivirals (protease inhibitors that target NS3):
    • boceprevir, telaprevir
  • life cycle inhibitors
    • entry, translation, post-processing, replication, assembly
  • nucleotide analogue + protease inhibitor, -IFN-a
    • highly curative for GT1, developing for GT3