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Immunology > Hepatitis > Flashcards

Hepatitis Flashcards

1
Q

Which form of Hepatitis is infectious?

Which are found in serum?

Which is enterically transmitted?

Which is parenterally transmitted?

A

Which Hepatitis is infectious? - Hepatitis A

Which are found in serum? - Hepatitis B and D

Which is enterically transmitted? - Hepatitis E

Which is parenterally transmitted? - Hepatitis C

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2
Q

Which forms of Hepatitis cause chronic viral hepatitis in the US?

A

Hepatitis C (3.9 million) and Hepatitis B (1.25 million)

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3
Q

Hepatitis A Virus characteristics (serotypes, transmission, acute vs chronic)

A
  • RNA picornavirus
    • Single serotype worldwide
    • Acute disease and asymptomatic infection
    • Fecal-oral transmission
    • Spread - contaminated food, water, raw shellfish
  • No chronic infection - protective antibodies develop in response to infection - lifelong immunity
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4
Q

Picornavirus structure

A
    • strand, icosahedral RNA virus
  • CAPSID stable to acid, drying detergents
  • mRNA translated into 1 polyprotein which is cleaved to form mature products
  • Virus is not cytolyic but is shed from cells
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5
Q

HAV is steadily released from infected _______

What is the immune response?

A

Hepatocytes; NK and cytotoxic T cells eliminate infected cells; Ab response also assists in viral clearance

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6
Q

Hepatitis A - Clinical features

Incubation period:

Jaundice by age group:

Rare complications:

A

Incubation period: Average 3- days; range 15-50 days

Jaundice by age group:

  • <6 yrs (<10%)
  • 6-14 years (40-50%)
  • >14 years (70-80%)

Rare complications:

  • Fulminant hepatitis
  • Cholestatic hepatitis
  • Relapsing hepatitis
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7
Q

How long is the incubation period for Hepatitis A infection?

A

3 weeks

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8
Q

Preparation of inactivated Hepatitis A vaccines (3 steps)

A
  • Cell culture adapted virus grown in human fibroblasts
  • Purified produce inactivated with formalin
  • Adsorbed to aluminum hydroxide adjuvant
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9
Q

Who is reccommended for HAV vaccination?

A
  • Infants
  • People working in or traveling to areas with high incidence of HAV
  • People with chronic liver disease
  • People working with HAV
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10
Q

Hepatitis E virus Characteristics

A
  • Enteric Virus
  • Calcivirus family
    • sense ss RNA virus
  • Icosahedral
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11
Q

Hepatitis E - Epidemiologic Features

A
  • Most outbreaks are associated with fecally contaminated drinking water
  • Minimal person-to-person transmission
  • US cases usually have history of travel to HEV endemic areas
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12
Q

Hepatitis B Virus ( Structure and Characteristics)

A
  • HepaDNAvirus (genotypes A-H)
  • Enveloped virus; receptor is sodium/bile acid co-transporter
  • Circular DNA genome, partly double-stranded (ds)
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13
Q

Outcome of Hepatitis B Virus Infection by Age at infection

A

If infected at birth - higher chance of chronic infection (chance decrease as we age)

If infected at older age - higher chance of symptomatic infection

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14
Q

Pathogenesis of Hep B

A
  • Enveloped virus enters through NTCB receptor
  • Genome enters, DNA synthesis occurs to form fully ds DNA
  • Genome goes to nucleus, transcribed to mRNA
  • mRNA translated in cytoplasm
  • mRNA reverse transcribed to ss DNA, DNA made partially ds
  • DNA encapsidated into new virion (on ER)
  • Virions enveloped and released as well as sub-viral particles of sAG (surface antigen)
  • DNA can integrate into chromosome and remain in cell
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15
Q

Risk factors for acute Hepatitis B in US

A
  • Heterosexual sex (32%)
  • Unrecognized (25%)
  • Intravenous drug use (13%)
  • Men having sex with men (MSM) - 12%
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16
Q

HBV spread through the body

A
  • Initial infection → blood → Liver → immune complexes → immune complex diseases OR…
  • Initial infection → blood → liver → viremia → bodily fluids → transmission
17
Q

Clinical outcomes of HBV infection in adults

A
  • 90% Resolution
  • 1% fulminant hepatitis
  • 9% HBsAG+ for > 6 months
    • 50% resolution
    • Asymtpmatic
    • Chronic persistent hepatitis
    • Chronic active hepatitis (rare)
      • Hepatic cell carcinoma
18
Q

Hepatitis D virus (delta)

A

Hepatitis D is a viroid - can only grow in Hepatitis B infected cells

  • small RNA, copied by host RNA polymerase II, catalytically active “ribozyme” that processes itself
  • Encodes 1 antigen, becomes packaged in Hepatitis B sAG
19
Q

Presence of HDV can make it more likely for HBV to lead to what condition?

A

Fulminant hepatitis

20
Q

Hepatitis D clinical features

Coinfection:

Superinfection:

A

Co-infection (with HBV): Severe acute disease; low risk of chronic infection

Superinfection (Subsequent to HBV): usually develop chronic HDV infection; high risk of severe chronic liver disease

21
Q

Why does chronic HVB infection correlate with a high incidence of hepatocellular carcinoma (HCC)

A
  • Injury to liver → proliferation of cells that are usually quiescent → genetic errors accumulate
  • Integration of viral DNA into host causes genomic instability
  • Virally-encoded “X” protein linked to signal transduction cascades decreases p53 activity (guardian of the genome)
22
Q

Prevention and Treatment of HBV

A
  • Blood supply screened
  • Vaccination - Subunit vaccine: recombinant HBsAG produced in yeast
  • Lifestyle precautions
  • Polymerase inhibitors, nuceloside analgos, IFN-α (new approaches to silencing HBV expression)
23
Q

Hepatitis C (Characterisitics)

A
  • Most prevalent “non A non B” hepatitis virus (NANBH)
  • Flavivirus
      • strand, RNA virus, enveloped virions
    • 9kb VLDL: 10 proteins - involves proteolytic processing
  • Encodes multiple immunomodulators enabling virus persistence
24
Q

Liver damage from HCV is due to…

A

Immunopathology; viral replication induces robust innate immune response

25
Q

Hepatitis C Viral lifecycle

A
  • Hepatocyte specific - 1012 virions/day
    • Entry
    • Uncoating
    • IRES-mediated translation/Proteolytic processing
    • Membrane associated RNA replication
    • Assembly
    • Maturation and release
26
Q

Sources of infections for persons with Hepatitis C

A
  • Injecting drug use (60%)
  • Sexual (15%)
  • Transfusion (10%)
  • Occupational (4%)
27
Q

What hpapened in 1992 to decrease HCV dramatically in the population

A

Widespread screening of blood supplies

28
Q

Clinical outcomes of HCV infection of adults

A
  • Recovery and Clearance (15%)
  • Persistent infection (85%)
    • Chronic Hepatitis
      • Liver failure (6%)
      • Cirrhosis (20%)
      • Hepatocellular carcinoma (4%)
29
Q

How/Why does Chronic HCV infection lead to a high incidence of hepatocellular carcinoma

A
  • The HCV core protein interacts with, and regulates, many cellular tumor suppressors
    • Induces steatosis (lipid accumulation) leading to oxidative stress and increases cell proliferation
  • HCV envelope protein (E2) inhibits natural killer cells
  • Viral proteins block action of p53
30
Q

According to GWAS (genome wide association studies), which gene plays a key role in the outcome of HCV infection

A

IL28b gene which incodes antiviral cytokine IFN-λ

31
Q

Which HCV genotype is most prevalent in the US?

A

HCV genotype 1

32
Q

Areas of HCV lifecycle targeted by drugs

A
  • Entry
  • IRES-dependent translation
  • Viral DNA replication
  • Particle assembly/release
33
Q

New 3 drug regimen

A
  1. Protease inhibitor
  2. NS5A inhibitor
  3. Nonnucleoside polymerase inhibitor

Immunology (17 decks)

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