Chapter 32: Hepatitis Viruses

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1

(...) is inflammation of the liver caused by viruses, bacteria, protozoa, toxins, and drugs.

hepatitis

2

What six viruses cause hepatitis?

  1. hepatitis A virus (HAV)
  2. hepatitis B virus (HBV)
  3. hepatitis C virus (HCV)
  4. hepatitis D virus (HDV)
  5. hepatitis E virus (HEV)
  6. hepatitis G virus (HGV)
3

What is a common name for HAV?

infectious hepatitis

4

What viral family does HAV belong to?

Picornaviridae (genus Hepatovirus)

5

What type of genome does HAV have?

RNA

6

What is the route of transmission for HAV?

fecal-oral

7

What viral protein is attached to the RNA of HAV at the 5’ end?

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VPg

8

What viral proteins are contained in the capsid of HAV?

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VP1 to VP4

9

Which HAV viral protein is released upon binding to its receptor, causing the virion structure to weaken?

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VP4

10

Which HAV viral protein forms a channel across the plasma membrane, allowing viral RNA to enter the cytoplasm?

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VP1

11

What is the incubation period of HAV?

15 to 45 days

12

What percentage of patients with HAV infection develop jaundice?

70% to 80%

13

What percentage of patients with HAV infection develop chronic liver disease?

none

14

What is used to diagnose HAV?

anti-HAV IgM antibodies

15

What is a rare but commonly known source of HAV infection?

Contaminated food, particularly shellfish from coastal areas close to sewage outlets (they act as a filter and concentrate the virus).

16

Why can HAV can spread rapidly?

Because most infected people are contagious during the asymptomatic incubation period.

17

What are the treatments for HAV? (2)

  1. serum globulin
  2. killed-virus vaccine
18

What is a common name for HBV?

serum hepatitis

19

What viral family does HBV belong to?

Hepadnaviridae (genus Orthohepadnavirus)

20

What type of genome does HBV have?

RNA

21

What is the route of transmission for HBV?

parenteral or sexual

22

What is the core antigen in HBV that encloses the viral DNA and the polymerase?

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HBcAg

23

What is the surface antigen of HBV that is located on the outer envelope?

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HBsAg

24

What is the viral produce produces by HBV that is secreted from infected cells into the bloodstream?

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HBeAg

25

What does presence of HBeAg indicate?

active HBV infection

26

What are the symptoms of hepatitis? (4)

  1. jaundice
  2. upper right quadrant pain
  3. pale stools
  4. dark urine
27

What symptoms can result when immune complexes form between antibodies and HBsAg? (4)

  1. arthritis
  2. maculopapular rash
  3. glomerulonephritis
  4. acute necrotizing vasculitis
28

Why does chronic HBV infection tend to occur in newborns?

Because they have insufficient cell-mediated immunity to clear the acute infection completely.

29

The initial phase of chronic HBV infection is referred to as the (...) phase, where the virus replicates to high levels.

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immune tolerance

30

What is clinically important about the immune tolerance of chronic HBV infection?

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Patients in this phase are highly infectious.

31

What are the levels of HBV DNA and ALT during the immune tolerance phase of HBV infection?

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HBV DNA is high, ALT is normal.

32

The immune tolerance phase of chronic HBV infection is followed by the (...) phase.

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immune clearance

33

What are the levels of HBV DNA and ALT during the immune clearance phase of HBV infection?

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HBV DNA decreases, ALT levels peak.

34

The immune clearance phase of chronic HBV infection is followed by the (...) phase.

inactive chronic

35

What is the serious potential complication of persistent carriage of HBV?

primary hepatocellular carcinoma

36

What is unique about primary hepatocellular carcinoma in regards to prevention?

It is a vaccine-preventable cancer (as is cervical cancer).

37

What is the is the most important laboratory test for the detection of early HBV infection?

HBsAg

38

What conclusion can be made if a patient tests positive for HBsAg?

The patient has an acute or chronic infection and can pass the virus to others.

39

What conclusion can be made if a patient tests positive for HBsAg on two occasions at least 6 months apart?

The patient is considered a chronic carrier.

40

What antibody is produced by the body in response to HBsAg?

anti-HBs

41

What conclusion can be made if a patient tests positive for anti-HBs?

The patient is immune to HBV because they either (a) were vaccinated, or (b) recovered from an acute infection.

42

What antibody is produced by the body in response to HBcAg?

anti-HBc

43

What conclusion can be made if a patient tests positive for anti-HBc?

The patient is either infected currently with HBV or was infected in the past.

44

What antibody is used to detect an acute HBV infection?

IgM anti-HBc

45

What conclusion can be made if a patient tests positive for IgM anti-HBc?

The patient was infected with HBV within the last 6 months.

46

What is the best marker of active HBV infection?

HBeAg

47

What conclusion can be made if a patient tests positive for HBeAg?

The patient has high levels of virus in the blood and can readily infect others.

48

What antibody is produced by the body in response to HBeAg?

anti-HBe antibody

49

What conclusion can be made if a patient tests positive for anti-HBe antibody?

The patient has chronic HBV infection, but there are lower levels of HBV in the blood.

50

What conclusion can be made if a patient tests positive for HBV DNA?

This indicates that the virus is multiplying and that the patient is highly contagious.

51

In chronic hepatitis, necrosis, inflammation, and fibrosis are observed, leading to the development of (...).

cirrhosis

52

Why is chronic hepatitis associated with very young and immunocompromised persons?

Progression to chronic hepatitis is associated with the inefficiency of the immune response.

53

What percentage of primary hepatocellular carcinoma can be attributed to chronic HBV infection?

80%

54

(...) occurs when the mucous membranes of the baby are contaminated by infected maternal blood during birth.

vertical transmission

55

What are the treatments for HBV? (3)

  1. pegylated interferon-α
  2. antiviral drugs
  3. HBV vaccine
56

What antiviral drugs are used to treat HBV?

  1. lamivudine
  2. adefovir
  3. entecavir
  4. tenofovir
57

What is the mechanism of action of lamivudine?

It is a reverse transcriptase inhibitor (prevents transcription of RNA to DNA).

58

What is the mechanism of action of adefovir?

It is a is an adenosine analog that competitively inhibits the HBV DNA polymerase.

59

What is the mechanism of action of entecavir?

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It is a is an guanosine analog that competitively inhibits the HBV DNA polymerase.

60

Tenofovir has the same mechanism of action as adefovir. What is an advantage of tenofovir over adefovir?

It has less kidney toxicity; thus, a higher dose can be used and better antiviral activity can be achieved.

61

What is a common name for HCV?

posttransfusion hepatitis

62

What viral family does HCV belong to?

Flavivirus (genus Hepacivirus)

63

What type of genome does HCV have?

RNA

64

What is the route of transmission of HCV?

parenteral (or sexual)

65

What two membrane glycoproteins are encoded in the HCV genome?

E1 and E2

66

What receptors on HCV facilitate virus uptake into hepatocytes? (2)

  1. scavenger receptor class B type I
  2. tetraspanin CD81
67

What enzyme mediates the generation of the negative-strand and positive-strand HCV RNA?

RNA-dependent RNA polymerase

68

Hepatitis C is the most common (...) in the United States.

blood-borne infection

69

What percentage of patients with acute HCV infection progress to chronic HCV infection?

70%

70

How soon after exposure are anti-HCV antibodies detectable in the blood?

6 month

71

How soon after infection is HCV RNA detectable in the blood?

2 to 3 weeks

72

What is the significance of the high replication rate of HCV (about 1012 virions per day)?

This high replication rate produces viral mutants that can escape detection by the immune system.

73

What HCV envelope glycoproteins elicit humoral and cell-mediated immune responses?

E1 and E2

74

In chronically HCV infected patients, the release of TNF-α can cause (...) that can cause liver damage.

cytokine storm

75

What population is at high risk for HCV?

Health workers with a history of accidental needlesticks.

76

What is the treatment for HCV? (4)

  1. pegylated interferon-α
  2. ribavirin
  3. telaprevir
  4. boceprevir

(Newer drugs include sofosbuvir, simeprevir, and daclatasvir)

77

What is pegylation?

Conjugation of poly(ethylene glycol) to interferon.

78

What is the purpose of pegylation of interferon?

It increases its circulation time in blood.

79

Which HCV genotypes are more likely to respond to interferon-α therapy?

2 and 3

80

What is a common name for HDV?

delta agent

81

What type of genome does HDV have?

RNA

82

What is the route of transmission of HDV?

parenteral or sexual

83

Why is HDV considered a “viral parasite”?

Because it requires the presence of HBV to replicate.

84

What HDV enzyme replicates the viral RNA in a after entry into the host cell?

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RNA polymerase II

85

HDV RNA forms a loop structure with enzymatic activity called a (...), which cleaves the viral genome to produce mRNA that encodes the small delta antigen.

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ribozyme

86

What is clinically significant about HDV-HBC co-infection?

It can cause hepatic encephalopathy and massive hepatic necrosis, fatal in 80% of cases.

87

What are the treatment for HDV infection?

  1. pegylated interferon (low efficacy)
  2. vaccination for HBV
88

What is a common name for HEV?

enteric non-Α, non-B hepatitis

89

What type of genome does HEV have?

RNA

90

What is the route of transmission for HEV?

fecal-oral

91

What population is at greater risk for mortality from HEV infection?

pregnant women

92

What is unique about the manifestations of HEV infection?

Hepatitis E may cause extrahepatic manifestations, including neurologic syndromes.

93

What is the treatment for HEV?

ribavirin

94

What viral hamily does HGV belong to?

Flavivirus

95

What type of genome does HGV have?

RNA

96

What is the route of transmission of HGV?

parenteral

97

What is unique about the replication HGV compared to other hepatitis viruses?

It replicates in lymphocytes, not hepatocytes.