Viral Hepatitis Flashcards

1
Q

What is the virus structure?

A
• are not able to replicate by themselves
but require host cells and its cellular
biochemical machinery to generate
progeny
• consist of DNA or RNA enclosed within a
virus-encoded protein coat
(nucleocapsid) and (sometimes) an
outer-most host cell membrane-derived
envelope
• attach to host cell using receptorbinding proteins targeting host cell
surface molecules that also serve as
virus-specific receptors
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2
Q

What are the clinical symptoms of hepatitis?

A
  • yellowing of skin and eyes (jaundice- increase bilirubin)
  • dark urine
  • clay-coloured stool
  • nausea and vomiting
  • loss of appetite
  • fever
  • abdominal pain
  • weakness
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3
Q

What are the biochemical and serological tests for hepatitis?

A
• biochemical blood tests for hepatitis
= liver enzymes (ALT, AST, ALP, GGT)
= other liver proteins (e.g. albumin, prothrombin)
= bilirubin (direct, indirect)
• serological and molecular tests for viral hepatitis
s
- Enzyme Immunosorbent Assays (EIA)
= Viral antigen
= Anti-viral antibody
- Molecular assays
= PCR
= Viral load
- Sequencing
= Genotype
= Antiviral resistance
• liver biopsy
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4
Q

Which hepatitis viruses are similar?

A

A and E (faecal, oral transmission)

B, C and D (parenteral, sexual)

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5
Q

Describe Hepatitis A Virus

A

• non-enveloped ss+ve RNA picornavirus
• at least 6 major genotypes, I-VI (type I is prevalent worldwide)
• incubation time is 10-50 days (avg 25-30 days)
• primarily children and young adults
• no seasonality (peaks may be seen in autumn)
• faecal-oral transmission
• abrupt onset, commonly with pyrexia
• resolves spontaneously (without chronicity – ie, no carrier
state) followed by life-long immunity
• fatality rate <0.5% in icteric cases (age dependent)
• inactivated virus vaccine (and immunoglobulin*) available
• treatment: supportive

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6
Q

Describe HAV transmission

A
  • Sewage-contaminated water
  • Shellfish filter off virus particles while feeding
  • Shellfish harvested; eaten raw or partially cooked
  • Virus ingested
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7
Q

What is the HAV Course of Infection?

A
- anti-HAV IgM in blood
• IgM antibody to HAV
• indicates recent HAV
infection
• persist for up to 4-6 months
post infection
- HAV RNA in blood
• present at the onset of
symptoms/signs
- anti-HAV IgG in blood
• IgG antibody to HAV
• indicates HAV infection (or
vaccine response)
• detectable by onset of
symptoms/signs
• persists for life
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8
Q

Describe Viral Hepatitis Prevalence

A
A= Sub Saharan Africa, India, SE Asia
B= Sub Saharan Africa, SE Asia, Russia
C= anywhere, European and north American
D= Europe, South America, Sub Saharan Africa
E= higher distribution, E Europe, South France
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9
Q

What is the HAV outcome?

A
Children vs Adults
=Subclinical infection= C 80-95%/ A 10-25%
=Icteric disease= C 5-20%/ A 75-90%
=Complete recovery= >98% both
-No chronic disease
=Fatality rate= C 0.1%/ A 0.3-2.1%
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10
Q

Describe Hepatitis B Virus

A

• Enveloped partially dsDNA hepadnavirus
• At least 8 main genotypes, A-H (type
A is prevalent in Europe)
• Incubation time is 40-180 days (avg 60-90 days)
• Primarily babies and young adults
• No seasonality
• Parenteral, vertical, sexual transmission (close contact)
• Insidious onset, sometimes apyrexial
• Virus remains in hepatocytes for life and may re-active under
immunosuppression (anti-HBcAb IgM may become detectable again)
• Chronic infection* (carrier state) develops in 5-10% of adults (but >95% of
neonates) and is associated with hepatocellular cancer
• Up to 2% fatality rate in icteric cases- liver failure

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11
Q

Describe HBV treatment

A

Recombinant HBV surface antigen vaccine (and immunoglobulin**) available
• Treatment (for chronic infection): Interferon alpha OR antivirals (eg, tenofovir,
entecavir); HBsAg seroconversion will occur in a small proportion of cases
treated with interferon alpha, but is even less likely to occur with antivirals;
however, antivirals are very effective in suppressing virus replication
(* Hepatitis B surface antigen-positive >6 months; ** Limited use)

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12
Q

Describe HBV structure

A
  • Virion Dane particle
  • Surface antigen= protein on envelope
  • HB particles
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13
Q

Describe HBV Nomenclature

A

Hepatitis-B Surface Antigen (HBsAg)
• Found in HBV envelope
• Indicates active HBV infection
• Found in serum during acute and chronic (carrier state) infection
• Anti-HBsAg (antibody to HBsAg)
= Indicates past HBV infection or immune response to HBV vaccine
or passive antibody transferred following administration of HBV Ig
(HBIG)

Hepatitis-B Core Antigen (HBcAg)
• Part of the HBV nucleocapsid
• Anti-HBcAg IgM (IgM antibody to HBcAg)
= Indicates recent HBV infection
= Persists for 4-6 months post infection
• Anti-HBcAg IgG (IgG antibody to HBcAg)
= Indicates recent or past infection with HBV
= Detectable by onset of acute symptoms and persists for life
Hepatitis-B E Antigen (HBeAg)
• Associated with HBV nucleocapsid
• Indicates active HBV infection
• Anti-HBeAg (antibody to HBeAg)
= Indicates HBV seroconversion
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14
Q

Describe HBV acute infection

A

Anti-HBc
-1 month= onset
Antibodies take time to develop-Surface antigen eliminated from blood when antibodies take over
E antigen= high viral load

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15
Q

Describe HBV chronic infection

A

-HBsAg
Surface antigen persists
Surface antibodies neutralise

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16
Q

HBsAg HBV Serological Profile

A

Incubation period
Acute HBV
Carrier (high infectivity)
Carrier (low infectivity)

17
Q

Anti-HBsAg HBV Serological Profile

A

Convalescence
Recovery
Vaccination
HBIG

18
Q

Anti-HBcAg IgM HBV Serological Profile

A

Acute HBV

Convalescence (-/+)

19
Q

Anti-HBcAg IgG HBV Serological Profile

A

Acute HBV
Convalescence
Recovery
Carrier (high and low infectivity)

20
Q

HBeAg HBV Serological Profile

A

Incubation period
Acute HBV
Carrier (high infectivity)

21
Q

Anti-HBeAg HBV Serological Profile

A

Convalescence
Recovery (+/-)
Carrier (low infectivity)

22
Q

HBV Prevalence in Europe, N America and Australia

A

HBsAg= 0.2-0.5%
Anti-HBs= 4-6%
Neonatal infection= Rare
Childhood infection= Rare

23
Q

HBV Prevalence in East Europe, Med, USSR, South America, SW Asia

A

HBsAg= 2-7%
Anti-HBs= 20-55%
Neonatal infection= Frequent
Childhood infection= Frequent

24
Q

HBV Prevalence in SE Asia, China, Africa

A

HBsAg= 8-20%
Anti-HBs= 70-95%
Neonatal infection= Very frequent
Childhood infection= Very frequent

25
Q

Describe vertical transmission of HBV in endemic regions (Asia, Africa)

A
  • New-borns, infants
  • 5% recovery from acute infection
  • 95% progression to chronic infection
  • 10-20% chronic carriers
26
Q

Describe contact transmission of HBV in endemic regions

A
  • Young children
  • 20% recovery from acute infection
  • 80% progression to chronic infection
  • 10-20% chronic carriers
27
Q

Describe parenteral and sexual transmission of HBV

A
  • Teenagers, adults
  • 90-95% recovery from acute infection
  • 5-10% progression to chronic infection
  • 0.5% chronic carriers
28
Q

Describe Hepatitis C Virus

A

Enveloped ss+ve RNA flavivirus
• At least 6 main genotypes, 1-6 (types 1 and 2 are prevalent in Europe)
• Incubation time is 15-160 days (avg 50 days)
• Primarily adults
• No seasonality
• Parenteral transmission (?sexual route)
• Acute phase very often completely asymptomatic
• Chronic infection established in 70-90% of cases
• Chronic infection (carrier state) is associated with hepatocellular cancer
• Up to 1% fatality rate in icteric cases

29
Q

Describe HCV treatment

A

• No vaccine available
• Treatment: Interferon alpha together with ribavirin OR direct-acting
antivirals (DAAs) such as protease inhibitors (eg, boceprevir, telaprevir)
and/or polymerase inhibitors (sofosbuvir)
• Increasingly, with the advent of DAAs, HCV is fast becoming a largely
curable (>90% [genotype independent]) infection

30
Q

What are the novel HCV antiviral drugs?

A
-Targeting translation and polyprotein processing
= Protease inhibitors
=NS5A
--Targeting RNA replication
=NNPI
=NS5B polymerase inhibitors
31
Q

Describe HCV course of infection

A
Anti-HCV Antibodies
• Antibodies to HCV
• Indicates recent and/or past HCV
infection
• Take up to 3 months to develop
HCV Antigen
• Reflects viraemia (active
infection)
HCV PCR
• Determines viraemia and, thus,
whether infection is an active one
(which requires treatment; success
depends on genotype)
IL28B genotype (single nucleotide polymorphism)
• Helped to determine susceptibility
to antiviral therapy, but is of
reduced/limited use now
32
Q

What is Viraemia?

A

Virus in blood = active infection; virus is actively replicating

33
Q

Describe Hepatitis D virus

A

enveloped circular ss-ve RNA
• at least 3 major genotypes, I-III (type I is most prevalent worldwide)
• similar to HBV, envelope contains HBsAg
• defective virus that needs HBV for
replication
• co-infection with HBV:
• severe acute disease
• low risk of chronicity
• super-infection on chronic HBV infection:
• chronic HDV infection
• high risk of severe chronic liver disease
• HBV vaccination provides indirect protection against HDV

34
Q

Describe Hepatitis E Virus

A

• non-enveloped ss+ve RNA hepevirus
• 7 genotypes, 1-4 in human [type 1 and
2
cause outbreaks in humans; type 3 and 4
are also found in animals (incl swine,
deer); type
3 is found worldwide]
• faecal-oral transmission
• incubation time 15-60 days (avg 40 days)
• overall fatality rate is 1%-3% (but 15%-
25% in pregnant women in outbreaks
[HEV genotype 1])
• no chronicity identified (except in the
immunocompromised)
• probably endemic in Europe but underdiagnosed
• no vaccine (HEV genotype 1 vaccine
available in China)
• treatment: Supportive; ribavirin can be
used to treat chronic infection

35
Q

What are other viral causes of Hepatitis?

A
  • Non-A/E hepatitis
  • Epstein-Barr virus (EBV)
  • Cytomegalovirus (CMV)
  • Herpes simplex virus type 1/2 (HSV-1/2)
  • Rubella virus
  • Enteroviruses
  • Yellow fever virus