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302: Scientific basis of medicine > Pathogenesis of viral hepatitis > Flashcards

Pathogenesis of viral hepatitis Flashcards

1
Q

Classifications of viral hepatitis

A

Subclinical

Acute hepatitis

Acute liver failure

chronic hepatitis

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2
Q

Histological staging of hepatitis- Stage 1

A

Fibrous expansion of portal areas

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3
Q

Histological staging of hepatitis- Stage 3

A

Expansion of most portal areas, occasional portal bridging

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4
Q

Histological staging of hepatitis- Stage 4

A

Fibrous expansion

Marked bridging

  • Portal-portal
  • Portal-central
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5
Q

Histological staging of hepatitis- Stage 5,6

A

Cirrhosis is probable/defined

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6
Q

Morphology of hepatitis virus

A

Surface antigen outside lipid bilayer
- HBsAg

Lipid bilayer

Core antigen
- HBcAg

DNA

Reverse transcriptase/ polymerase within core

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7
Q

HBV replication

A
  1. Virus enters cell
  2. Outer shell is shed and core particle enters nucleus.
  3. Reverse transcription via reverse transcriptase of RNA template produces complementary DNA.
  4. DNA undergoes normal transcription and translation to make core proteins.
  5. Uses the infected cell to package its RNA and is transporter out of cell via vesicle
  6. Core particle can be recycled whilst packaging to re-enter nucleus.
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8
Q

HBsAb development

A

Neutralising antibody that forms in the later stage of viral clearance.

Binds to HBsAg and prevents its uptake by uninfected hepatocytes.

Provides life long immunity from further infections

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9
Q

Factors that contribute to persistent infection

A

Age of infection

  • HBeAg induces tolerance to HBcAg
  • Leads to suppressed elimination of infected cells but switching response to Th2

Immunosuppression

  • Inadequate cell-mediated immunity
  • Poor CD4/8 response in liver due to high viral load or antiviral therapy

HBV X protein interferes with Ag processing and presentation

Foxp3 on Treg cells suppress T cell responses to HBV

CD28 upregulation promotes apoptosis
- downregulates T cell responses

CTLA4 switch off cell responses

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10
Q

Role of IL-10 in persistent infection

A

Downregulates antiviral immune responses

Inhibits IFN-g and IFN-a
- Suppresses CD4 and CD8

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11
Q

Persistent infection with HBV

- Age

A

95% of immunocompetent adults clear the infection

90% of neonates infection develop chronic infection

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12
Q

HCV

  • Features
  • Chronicity
  • Vaccination?
A

RNA virus
- rapidly replicates

80% develop chronic infection

No vaccine

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13
Q

Features of resolving HCV infection

  • Viremia
  • T cell response
  • Neutralising Ab
A

Early phase
- As viral load increases, t cell responses increase shortly after (recognise HCV peptides, produces TNF, IFN)

  • Th2 cells activate B cells to produce neutralising antibodies

Later phase

  • Neutralising antibodies help to remove virus
  • T cell responses persist
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14
Q

Features of chronic HCV infection

  • Viremia
  • T cell response
  • Neutralising Ab
A

Neutralising antibodies are present but T cell responses are poor
- Viral load persists

Ab does not prevent re-infection

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15
Q

Hepatitis A

  • Cause
  • Incubation period
  • Endemic areas
  • Presentation
A

Contracted via fecal-oral route, shellfish

Incubation period
- 2-6 weeks.

Endemic areas
- Africa, South aemrica

Presentation

  • Fatigue, malaise, fever
  • Later= jaundice, hepatosplenomegaly
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16
Q

Hepatitis A

  • Diagnosis
  • Treatment
A

Tests

  • LFTs: raised ALT and AST
  • Anti-Hep A IgG

Treatment
- Prophylaxis: active immunisation

17
Q

Hepatitis B

  • Transmission
  • Incubation period
  • Presentation
  • Endemic regions
A

Bodily fluids

  • Blood contact (IVDU)
  • sexual contact

Incubation period
- 1-6 months

Presentation

  • Malaise, fever, anorexia, nausea
  • Arthralgia
  • Later= jaundice, hepatosplenomegaly

Endemic regions

  • Far east
  • Africa
  • Mediterranean
18
Q

Hepatitis B

  • Diagnosis
  • Treatment/ vaccine
A

Diagnosis

  • Initial stage: HBsAg, HbeAg. HBsAg >6 months += carrier
  • HBV PCR
  • Later= antibodies against HBcAg and HBsAg
  • HBsAg alone= vaccination

Vaccine
- Passive immunisation (anti-HBV Ig) after high risk exposure

Treat with anti-viral

19
Q

Hepatitis C

  • Spread
  • Incubation period
  • Presentation
  • Endemic regions
A

Spread
- Sex, blood

Incubation period
- 2 weeks- 6 months

Presentation

  • May be asymptomatic for a while
  • Cirrhosis signs: jaundice, ascites, splenomegaly
20
Q

Hep C

  • Diagnosis
  • Treatment
A

HCV PCR

Anti-HCV antibody

Treatment
- Protease inhibitors

21
Q

Hep E

  • Spread
  • Incubation period
  • Endemic areas
  • Diagnosis
A

Fecal-oral spread

Incubation period
- 2-6 weeks

Endemic

Presentation

  • Jaundice
  • Nausea, fatigue, pruritus

Diagnosis
- IgM anti-HEV

302: Scientific basis of medicine (28 decks)

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