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IAHI Block 3 > Hepatitis > Flashcards

Flashcards in Hepatitis Deck (33):
1

Which form of Hepatitis is infectious?

Which are found in serum?

Which is enterically transmitted?

Which is parenterally transmitted?

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

2

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

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

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3

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

  • 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

4

Picornavirus structure

  • + 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

HAV is steadily released from infected  _______

What is the immune response?

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

6

Hepatitis A - Clinical features

Incubation period:

Jaundice by age group:

Rare complications:

 

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

7

How long is the incubation period for Hepatitis A infection?

3 weeks

8

Preparation of inactivated Hepatitis A vaccines (3 steps)

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

9

Who is reccommended for HAV vaccination?

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

10

Hepatitis E virus Characteristics

  • Enteric Virus
  • Calcivirus family
  • + sense ss RNA virus
  • Icosahedral

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11

Hepatitis E - Epidemiologic Features

  • 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

12

Hepatitis B Virus ( Structure and Characteristics)

  • 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

Outcome of Hepatitis B Virus Infection by Age at infection

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

Pathogenesis of Hep B

  • 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

15

Risk factors for acute Hepatitis B in US

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

 

16

HBV spread through the body

  • Initial infection → blood → Liver → immune complexes → immune complex diseases OR...
  • Initial infection → blood → liver → viremia → bodily fluids → transmission 

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17

Clinical outcomes of HBV infection in adults

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

18

Hepatitis D virus (delta)

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

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

Fulminant hepatitis

20

Hepatitis D clinical features

Coinfection:

Superinfection:

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

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

  • 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

Prevention and Treatment of HBV

  • 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

Hepatitis C (Characterisitics)

  • 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

Liver damage from HCV is due to...

Immunopathology; viral replication induces robust innate immune response

25

Hepatitis C Viral lifecycle

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

26

Sources of infections for persons with Hepatitis C

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

27

What hpapened in 1992 to decrease HCV dramatically in the population

Widespread screening of blood supplies

28

Clinical outcomes of HCV infection of adults

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

29

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

  • 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

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

IL28b gene which incodes antiviral cytokine IFN-λ

31

Which HCV genotype is most prevalent in the US?

HCV genotype 1

32

Areas of HCV lifecycle targeted by drugs

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

33

New 3 drug regimen

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