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Parasitology/Virology > Hepatitis Viruses > Flashcards

Hepatitis Viruses Flashcards

1
Q

What are laboratory indications of liver failure/liver inflammation?

A

Elevated AST or ALT

Increased prothrombin time or INR

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2
Q

What is the definition of hepatitis?

A

Inflammation of liver which can lead to damage and potentially liver dysfunction

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3
Q

What are classic signs and symptoms of acute hepatitis?

A

Fatigue, nausea, vomiting, malaise, headache, chills
Abdominal pain (RUQ), loss of appetite
Chalky stools
Jaundice and icterus (bilirubin in skin & sclerae)

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4
Q

Is hepatitis B a RNA or DNA virus?

A

DNA virus (hepadnavirus)

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5
Q

What are the different core antigens of Hepatitis B?

A

Core antigen HBcAg

e antigen HBeAg

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6
Q

What is the e antigen of Hepatitis B?

A

Role not well characterized

Acts as an indicator of active viral replication and increased transmissibility

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7
Q

What is the surface antigen of Hepatitis B?

A

HBsAg - forms viral component of lipoprotein envelope

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8
Q

What is cccDNA?

A

Covalently closed circular DNA (tightly supercoiled)

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9
Q

What is the life cycle of HBV?

A

Binds via surface antigen
Uncoats into cytoplasm
Nucleocapsids release ‘relaxed’ circular DNA (rcDNA) into nucleus
rcDNA is repaired to yield cccDNA (covalently closed circular DNA)
cccDNA is transcribed to 4 viral mRNA
- Smaller mRNAs transplated into structural proteins
- Larger mRNA packaged with RT into core particle
- Larger mRNA is finally transcribed by reverse transcriptase into negative strand DNA
Virion can then be released

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10
Q

How long does cccDNA persist in host?

A

Indefinitely, never removed completely from nuclei of host

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11
Q

What causes the liver damage associated with Hepatitis B?

A

Immune response (primarily cytotoxic T cell response) to viral antigens expressed on hepatocyte cell surface

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12
Q

How many genotypes are there of Hep B?

A

8 (A-H)

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13
Q

What are modes of HBV transmission?

A

Sexual, parenteral, perinatal

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14
Q

What body fluids have highest concentration of Hep B virus?

A

Blood, serum, wound exudates

Semen, vaginal fluid, saliva are moderate

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15
Q

What age will show clinical symptoms of Hep 5?

A

Usually > age 5

Under age 5 don’t have a fully functional immune system, and immune response is what causes clinical presentation

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16
Q

What age is more likely to develop chronic infection from acute infeciton?

A

Usually < age 5
Immune system is not fully developed and cannot fight off disease as well
(>90% of children progress to chronic, <5% of adults)

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17
Q

What are the different serologic markers of Hepatitis B?

A 
HBsAg
HBeAg
Anti-HBs
Anti-HBe
Anti-HBc (IgM)
Anti-HBc (IgG)
HBV DNA
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18
Q

What is the definition and clinical use of HBsAg?

A

Hepatitis B surface antigen
General marker of infection
First serologic marker to appear
Persistence for >6 months = chronic infection

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19
Q

What is the definition and clinical use of HBeAg?

A

Hepatitis B e antigen

Indicates active replication of virus

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20
Q

What is the definition and clinical use of Anti-HBs?

A

Antibody to hepatitis B surface antigen
Indicates recovery from natural infection and/or immunity
Detectable after Hep B immunization

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21
Q

What is the definition and clinical use of Anti-HBe?

A

Antibody to hepatitis B e antigen
Marker of reduced level of replication
Not often done in acute evaluation

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22
Q

What is the definition and clinical use of Anti-HBc (IgM)?

A

Antibody to hepatitis B core antigen

Marker of current acute hepatitis B infection

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23
Q

What is the definition and clinical use of Anti-HBc (IgG)?

A

Antibody to hepatitis B core antigen

Marker of current or past infection

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24
Q

What is the definition and clinical use of HBV DNA?

A

Hepatitis B virus genomic DNA
Marker of HBV replication
Used for monitoring response to therapy

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25
Q

What is the first serologic marker of HBV to appear?

A

HBsAg

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26
Q

Can you ever see expression of HBsAg and anti-HBs serologic markers at the same time?

A

No, there is window period between these two

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27
Q

What is serologic profile of someone with an active acute Hepatitis B infection?

A 
HBsAg POSITIVE
Anti-HBs NEGATIVE
Anti-HBc (IgM) POSITIVE
Anti-HBc (IgG) NEGATIVE
HBV DNA POSITIVE
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28
Q

What is serologic profile of someone with a resolved Hepatitis B infection?

A 
HBsAg NEGATIVE
Anti-HBs POSITIVE
Anti-HBc (IgM) NEGATIVE
Anti-HBc (IgG) POSITIVE
HBV DNA NEGATIVE
29
Q

What is serologic profile of someone who developed chronic Hep B disease?

A 
HBsAg POSITIVE (at least 6 months apart)
Anti-HBs NEGATIVE
Anti-HBc (IgM) NEGATIVE
Anti-HBc (IgG) POSITIVE
HBV DNA POSITIVE
30
Q

What is a key group of individuals who should be screened for Hep B?

A

Persons born in countries with >2% HBsAg prevalence (endemic areas)

31
Q

What serologic marker will be detectable after HBV immunization?

32
Q

Who receives treatment for HBV?

A

Patients who have evidence of liver damage (elevated ALT or significant fibrosis/inflammation)
Usually treat indefinitely

33
Q

What is the major treatment endpoint?

A

Reduction of HBV DNA

34
Q

What is the most common therapy for HBV?

A

Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)
(Usually tenofovir or entecavir)

35
Q

What options are available for hepatitis B prevention?

A

Hepatitis B immunoglobulin

Hepatitis B vaccine

36
Q

What is unique about Hepatitis D?

A

Requires co-infection with Hepatitis B

37
Q

How is diagnosis of Hepatitis D made?

A

Serology

Anti-HDV IgM (acute) or IgG (chronic)

38
Q 
What is the diagnosis of this serologic profile?
Anti-HCV positive
Anti-HBs positive
Anti-HBc (IgG) positive
HBsAg negative
Anti-HAV negative
A

Chronic hepatitis C with resolved HBV

39
Q

Is Hepatitis C a RNA or DNA virus?

40
Q

How many genotypes are there of Hepatitis C?

A

7 genotypes (1-7)

41
Q

What is unique about the life cycle of HCV?

A

All occurs outside of the nucleus

Uses host proteases and host cellular membranes to form membranous web on ER where RNA replication occurs

42
Q

What is the main target of HCV therapies?

A

Non-structural proteins (protease, polymerase, NS5A)

43
Q

How do HCV virions get released from the cell cytoplasm?

A

Uses lipid secretion pathways

44
Q

Why do more people progress to chronic infection with HCV than with HBV?

A

HCV is highly mutagenic

Harder to develop strong immune response –> more likely to progress to chronic

45
Q

What cell does HCV primarily infect?

A

Hepatocytes

46
Q

What is the function of HCV NS3-4A core protein?

A

Blunts host innate immune response to virus

47
Q

What causes liver damage in Hep C infection?

A

Immune response (cytotoxic T cells), not the direct cytopathic effect of virus

48
Q

What liver disease can cause hepatocellular carcinoma?

A

Hep B, Hep C, chronic alcoholism

49
Q

What are modes of transmission of HCV?

A

IDU > Sexual > Transfusion

50
Q

When will symptoms of HCV develop?

A

Acute infection - Usually asymptomatic
Chronic infection - May be asymptomatic for years
Symptoms may not be present until cirrhosis develops

51
Q

What is the most important factor associated with disease progression in HCV?

52
Q

Is HCV viral load associated with disease progression?

53
Q

How is HCV diagnosed?

A

ELISA screening for HCV antibodies

Confirmed with HCV viral load

54
Q

Who receives treatment for HCV?

A

Based on degree of liver damage

Evidence of fibrosis (stage 2 or higher) on liver biopsy

55
Q

What is the standard of care for therapy for HCV?

A

Moving away from Inferferon regimens

Now using protease inhibitors, polymerase inhibitors, and NS5A inhibitors

56
Q

What is the goal of therapy of HCV?

A

Attain sustained virologic response (SVR) - undetectable viral load 3-6 months after therapy completion
Is essentially a CURE

57
Q

What drugs are the mainstays of treatment for HCV?

A

Sofosvuvir - NS5B inhibitor
Simeprevir - NS3-4A protease inhibitor
Ledipasvir - NS5A inhibitor

58
Q

What is the diagnosis of these labs and seroglogic profile?
Labs: elevated ALT/AST, elevated prothrombin and INR
Anti-HCV positive
Anti-HBc negative (IgM and IgG)
HBsAg negative
Anti-HBs positive
Anti-HAV (IgM) positive

A

Hepatitis A

theoretically could be HCV but overwhelming majority of those patients are not symptomatic

59
Q

Is Hepatitis A an RNA or DNA virus?

60
Q

What is the mode of transmission of Hepatitis A?

A

Fecal-oral

Close contact, contaminated food, “raw oysters” is buzzword

61
Q

What is the difference in clinical presentation between Hepatitis A and acute Hepatitis B?

A

Trick question! None

62
Q

What is unique for Hepatitis A compared to other hepatitis viruses?

A

No chronic form

63
Q

What is the therapy for Hepatitis A?

A

Supportive therapy

64
Q

What can be done to prevent Hepatitis A infection?

A

Hep A immunoglobulin

Hep A vaccine

65
Q

Which hepatitis viruses have an immunoglobulin that can be given for passive immunization?

A

Hep B and A

66
Q

Is hepatitis E an RNA or DNA virus?

67
Q

What are two major differences between Hepatitis A and Hepatitis E?

A

Hep E has chronic form that can develop in people who are severely immunosuppressed
Hep E has high mortality rate in pregnant women

68
Q

What is the mode of transmission of Hepatitis E?

A

Fecal-oral (associated with contaminated water)

Parasitology/Virology (19 decks)

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