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SMP - MIM Part 2 > Lecture 13 - Hepatitis Viruses > Flashcards

Lecture 13 - Hepatitis Viruses Flashcards

1
Q

What are the 5 hepatitis viruses?

A 
hepatitis A virus (HAV) 
hepatitis B virus (HBV)
hepatitis C virus (HCV)
hepatitis D (delta) virus (HDV)
hepatitis E virus (HEV)
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2
Q

Genome of HAV and HEV?

A

RNA

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3
Q

Virus family of HAV?

A

Picornaviruses

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4
Q

Virus family of HBV?

A

Hepadna virus

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5
Q

Which hepatitis virus has a replication similar to HIV? Implication?

A

HBV => some drugs (some of the nucleoside analogs) work against both viruses

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6
Q

Virus family of HCV?

A

Flavi virus (same as Dangue and West Nile viruses)

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7
Q

Genome of HDV?

A

RNA

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8
Q

What is unique about HDV?

A

Requires HBV infection to infect

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9
Q

How are hepatitis viruses different?

A

They are from different virus families with distinct virologic properties:

  1. Structure
  2. Transmission
  3. Epidemiology
  4. Treatment and prevention options
  5. Outcome (acute vs. chronic infection)
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10
Q

How are hepatitis viruses similar?

A

Similar symptoms, esp. during acute infection

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11
Q

Can other viruses cause hepatitis?

A

YUP - but are not as restricted to the liver as hepatitis viruses (e.g. yellow fever)

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12
Q

Lab diagnosis for viral hepatitis? 2

A
  1. High serum levels of liver enzymes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH)
  2. Specific virus markers
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13
Q

How to differentiate between hepatitis viruses?

A
  1. Good history

2. Lab tests

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14
Q

Which 2 hepatitis viruses cause extra-hepatic symptoms?

A

B and C

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15
Q

Which 3 hepatitis viruses cause chronic infections?

A

B, C, and D

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16
Q

Definition of chronic infection?

A

> 6 mos

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17
Q

Number of serotypes of HBV?

A

Only one

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18
Q

5 symptoms of acute viral hepatitis?

A
  1. Typical symptoms of viral infection (e.g. fever)

INDICATIONS OF HEPATITIS:

  1. Jaundice
  2. Abdominal pain
  3. Dark urine
  4. Itching
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19
Q

Are hepatitis viruses generally cytolytic?

A

NOPE

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20
Q

Pathogenesis of acute hepatitis?

A

Cytotoxic effects of cell-mediated immune responses

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21
Q

Pathogenesis of chronic hepatitis? 2

A
  1. Ineffective immune responses that nevertheless cause inflammation and low level cytotoxicity
  2. Extrahepatic effects due to circulating immune complexes (mainly HCV)
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22
Q

What 3 viruses cause the vast majority of acute viral hepatitis in the US? List in increasing order.

A
  1. HAV
  2. HCV
  3. HBV
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23
Q

Why are estimated number of viral hepatitis infections higher than reported infections?

A

Because some infections may be asymptomatic (esp. B and C acute infections)

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24
Q

Higher numbers of acute or chronic infections in the US?

A

More chronic infections

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25
Q

Fraction of patients with chronic HBV that die prematurely?

A

1 in 4

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26
Q

Fraction of patients with chronic HCV that die prematurely?

A

5-10%

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27
Q

Describe the HAV.

A

Small, non-enveloped virus that is highly stable in the environment due to protein shell

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28
Q

What is the HAV inactivated by?

A
  1. Heat

2. Water chlorination

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29
Q

HAV transmission?

A

Fecal-oral: shedding in stool precedes symptoms and is not related to their severity

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30
Q

Number of HAV serotypes?

A

Only 1

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31
Q

Implications of a virus only have 1 serotype?

A
  1. Recovery leads to lifelong protection against re-infection
  2. Good candidate for vaccine
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32
Q

Describe the acute hepatitis caused by HAV infection.

A
  1. Variable intensity (severity increases with age and pre-existing liver disease)
  2. Frequently asymptomatic
  3. Fulminant hepatitis <1% of cases
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33
Q

How long does recovery from HAV infection take?

A

Can take months, particularly in older individuals

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34
Q

When is HAV present in the stool? What to note?

A

Weeks 2-5.5 of infection

NOTE: regardless of symptoms

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35
Q

What is the period of clinical illness with HAV infection?

A

Weeks 2.5-6.5 of infection

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36
Q

Peak of HAV infection? What does it coincidence with?

A

4.5 weeks => IgM anti-HAV antibodies

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37
Q

What are IgG antibodies indicative of?

A

Previous viral exposure (infection or vaccine)

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38
Q

What are IgM antibodies indicative of?

A

Current acute infection

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39
Q

Are the symptoms of HAV specific to the virus?

A

NOPE

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40
Q

Is HAV infection always symptomatic?

A

NOPE

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41
Q

What 4 factors in the patient history can point to an HAV infection?

A
  1. They traveled to an endemic area (Mexico, Africa, parts of South America, India, and Greenland)
  2. They were part of an outbreak due to contaminated food or water
  3. They are MSM
  4. They had close personal contact with an infected person
42
Q

Important source of HAV transmission? Explain.

A

Young children because of poor hygiene and because frequently asymptomatic while shedding the virus

43
Q

How to treat HAV infection?

A

No specific therapy, just supportive care

44
Q

4 ways to prevent HAV infections?

A
  1. Hygiene (e.g. hand washing)
  2. Sanitation (e.g. clean water sources)
  3. Hepatitis A vaccine (pre-exposure)
  4. Immune globulin (pre- and post-exposure)
45
Q

Describe the HAV vaccine.

A

Inactivated virus administered in 2 doses, 6 mos apart => Vaqta, Havrix, or Twinrix

46
Q

For what 5 populations is the HAV vaccine recommended?

A
  1. Children at 12-23 months
  2. Travelers to endemic areas
  3. MSM
  4. Child care workers
  5. Patients with chronic HBV, HCV
47
Q

Describe the HBV.

A

Small enveloped virus

48
Q

Is the HBV vaccine therapeutic?

A

NOPE

49
Q

HBV infection transmission? 3

What to note?

A
  1. Parenteral
  2. Perinatal
  3. Sexual

NOTE: in 56% of cases, mode of transmission is unknown

50
Q

Symptoms of acute HBV and HCV infections?

A

Frequently asymptomatic

51
Q

Fatality rate of acute HBV infection?

A

Low: 0.5-1% among reported cases

52
Q

Consequence of chronic HBV infection?

A

High risk of life-long:

  1. Chronic liver disease

2 Liver cirrhosis

  1. Primary hepatocellular carcinoma (leading cause is HBV)
  2. Liver failure
53
Q

Is there a cure for primary hepatocellular carcinoma?

A

NOPE

54
Q

Describe the 2 antibodies against HBV.

A
  1. Anti-surface protein: protective and only appear during acute infection
  2. Anti-core protein: NOT protective and appear during both acute and chronic infections
55
Q

What indicates recovery from acute HBV infection? 3

A
  1. Loss of symptoms
  2. Loss of HBsAg
  3. Appearance of anti-HBs
56
Q

What does the presence of HBsAg in the blood indicate?

A

Presence of virus (acute or chronic)

57
Q

What does the presence of HBe/anti-HBe in the blood indicate?

A

Can be useful for assessing status of chronic infection and need for therapy

58
Q

Test result:
HBsAg (+)
IgG anti-HBc (+)

DIAGNOSIS?

A

Acute or chronic HBV

59
Q

Test result:
HBsAg (+)
IgG anti-HBc (+)
IgM anti-HBc (+)

DIAGNOSIS?

A

Acute HBV

60
Q

Test result:
HBsAg (+)
IgG anti-HBc (+)
IgM anti-HBc (-)

DIAGNOSIS?

A

Chronic HBV

61
Q

Test resulr:
HBsAg (+)
Total anti-HBc (+)
2X > 6months apart

DIAGNOSIS?

A

Chronic HBV

62
Q

In what % of patients is the HBV vaccine not successful?

A

5%

63
Q

Chance of infection with HBV upon exposure from needle?

A

1 in 3

64
Q

What does the chance of a chronic infection developing from HBV depend on?

A
  1. Age of individual when exposed: the younger, the higher the chances
  2. Symptoms: less symptoms, higher risk
65
Q

Describe the HBV vaccine.

A

Recombinant HBsAg expressed in yeast administered in 3 doses

66
Q

Who gets the HBV vaccine?

A

All newborns

67
Q

What is HBV immune globulin (HBIG) used for? 3

A
  1. Post-exposure prophylaxis
  2. Infants born to HBV positive mothers
  3. Post-liver transplant
68
Q

2 important things to learn about HBV replication? Implication for #2?

A
  1. Virus uses a reverse transcriptase (like HIV)
  2. Virus does not need to integrate in the genome and has a stable intercellular intermediate (cccDNA) that is present (50 copies) in infected hepatocytes and we do not know how to get rid of it => HBV therapy has to be life-long
69
Q

Describe HCV.

A

Enveloped virus with no stable intracellular form.

70
Q

How many genotypes of HCV?

A

Multiple strains

71
Q

What is partly responsible for the high rate of chronic HCV infections?

A

RNA genome and its rapid changes in envelop gene

72
Q

Is there a vaccine for HCV infections?

A

NOPE

73
Q

Which 3 hep viruses have the longest incubation periods? List in decreasing order.

A
  1. HCV: 2-26 weeks (6-7 weeks on average)
  2. HBV: 45-180 days
  3. HAV: 15-45 days
74
Q

Fatality rate of acute HCV infection?

A

Low rate

75
Q

Are HCV or HBV infections more likely to become chronic?

A

HCV (60-85% of them)

76
Q

Symptoms of chronic HCV infection?

A

Asymptomatic but may eventually lead to active hepatitis (50% of cases)

77
Q

Mortality rate of chronic HCV infection?

A

5-10%

78
Q

What % of chronic HCV infections have extrahepatic manifestations?

A

50%

79
Q

% of HCV patients with chronic hepatitis that have further complications leading to liver failure?

A

20%

80
Q

What are the 5 factors associated with progression of chronic HCV?

A
  1. Age
  2. Alcohol
  3. HBV infection
  4. HIV infection
  5. Male > female
81
Q

Plasma marker of acute HCV infection? What does it coincide with?

A

HCV RNA

Coincides with symptoms and ALT level

82
Q

Sign of HCV infection recovery?

A
  1. HCV RNA disappears

2. Anti-HCV antibodies

83
Q

Markers of progression into HCV chronic infection? Implication?

A
  1. Symptoms may or may not go away
  2. ALT levels go up and down after the acute spike
  3. HCV RNA levels are not constant and there is sporadic absence of detectable RNA in serum => need to test more than once (separated by several weeks) to distinguish between chronic and acute
84
Q

Symptoms of acute HCV infection?

A

Usually asymptomatic, but could also see typical signs of hepatitis

85
Q

Symptoms of chronic HCV infection?

A

Non-specific (e.g. chronic fatigue)

86
Q

What does anti-HCV antibodies in the blood indicate?

A
  1. Resolved acute infection
    OR
  2. Chronic current infection
87
Q

HCV transmission?

A

Primarily via exposure to infected blood

88
Q

4 risk factors for HCV infection? Which is most important?

A
  1. Injection drug use***
  2. Sex with infected person
  3. High risk practices: multiple sex partners, unprotected sex, etc.
  4. Occupational exposure
89
Q

How has prevalence of HCV infections changed since the 90s?

A

Dramatic reduction

90
Q

2 ways to prevent HCV infections?

A
  1. Universal precautions

2. Screen blood and organ donors

91
Q

Is post-exposure prophylaxis available for HCV infections?

A

NOPE

92
Q

What is the goal of therapies against HCV?

A

Sustained viral response (SVR) = sustained loss of viral RNA for 12 weeks after therapy ends for the infection to be considered cured

93
Q

2 therapies for HCV infections?

A
  1. Interferon

2. Direct-acting antiviral agents (DAA)

94
Q

Describe HCV replication. Which are 2 targets for antiviral agents? What to note?

A

Large protein complex is formed intracellularly in order to replicate

  1. Processing of viral proteins into individual functional units by HCV NS3-4A protease
  2. Synthesis of viral RNAs by HCV polymerase (NS5B) and accessory protein NS5A

NOTE: need to target both or else mutations will escape treatment

95
Q

Can all anti-virals be used against all HCV infections?

A

NOPE - varies by HCV genotype (except for NS5B targets) and stage of liver disease

96
Q

What cohort has the highest HCV incidence?

A

1945-1965 birth cohort

97
Q

Are vaccines available for HEV and HDV infections?

A

NOPE

98
Q

How are HEV and HDV transmitted?

A
  1. HEV: fecal-oral

2. HDV: parenterally

99
Q

HEV: chronic, acute, or both?

A

Only acute

100
Q

HDV: chronic, acute, or both?

A

Both

101
Q

How to determine level of chronic disease?

A

Liver biopsy

SMP - MIM Part 2 (13 decks)

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