Lecture24 - Viral Hepatitis Flashcards

1
Q

Cause of jaundice

A

Hyperbilireubinaemia

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2
Q

Type of cancer that hepatitis can lead to

A

Hepatocellular carcinoma

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3
Q

Effect of hepatitis viruses on host cells

A

Cytopathic (cause pathology), but not cytolytic (don’t lyse host cells)

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4
Q

Different prognosis of hepatitis disease based on age of transmission

A

Younger exposure leads to less severe acute disease, greater likelihood of chronic disease Older exposure leads to more severe acute disease, lesser likelihood of chronic disease

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5
Q

Is there any cross-protection between hepatitis viruses?

A

No

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6
Q

Enteric hepatitis viruses

A

Hep A and E

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7
Q

Chronic hepatitis viruses

A

Hep B, D and C

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8
Q

How are hep B, C and D transmitted?

A

Percutaneously, permucosally

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9
Q

How to diagnose acute hepatitis

A

1) Serological tests (EG: ELISA) 2) Nucleic acid tests (EG: PCR). This is less effective than ELISA.

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10
Q

ELISA tests for acute hepatitis 1) 2) 3)

A

1) Over 90% sensitive, over 99% specific 2) IgM antibodies detectable at between 1-2 weeks after exposure. 3) Rising IgG titres indicates an acute infection

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11
Q

Hepatitis A viral family

A

Picornaviridae

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12
Q

Hep A virion characteristics 1) 2) 3)

A

1) Non-enveloped, (+)ssRNA virus 2) 30nm particle, resistent to stomach acid 3) 7.5nt genome, coding for a single polyprotein

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13
Q

Serotypes of hep A

A

Single serotype worldwide. All viral strains elicit the same antibody response.

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14
Q

Hep A and hep E life cycles 1) 2) 3) 4)

A

1) Ingested from contaminated food or water 2) Replication in intestinal epithelia 3) Enters blood, replicates in the liver 4) Excreted via the bile canaliculi into faeces

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15
Q

Fulminant infection

A

Extremely-rapid onset

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16
Q

A spike in what coincides with hepatitis symptoms?

A

Liver enzyme ALT

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17
Q

Hep A incubation period

A

Average 30 days. 15-50 day range

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18
Q

Hep A symptoms by age group 1) 2) 3)

A

1) Under 6 years, 10% show symptoms 2) Between 6-14 years, 40-50% 3) Over 14 years, 70-80%

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19
Q

Hep A symptoms

A

Jaundice, vomiting, pale faeces, dark urine

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20
Q

Hep A complications

A

Fulminant hepatitis (rarely), cholestatic hepatitis

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21
Q

Chronic sequelae of hep A and E

A

None

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22
Q

Typical serological course of hep A infection

A

HEP A

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23
Q

Length of hep A symptoms

A

2-3 weeks

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24
Q

Hep A prevention and treatment 1) 2) 3) 4)

A

1) Sanitation 2) Pre-exposure (for travellers) or post-exposure (within 14 days of exposure) immunoglobulin 3) Supportive rehydration and nutrition 4) Vaccine

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25
Q

Hep A vaccine 1) 2) 3) 4) 5) 6)

A

1) Virus grown in a diploid cell culture 2) Inactivated whole virus with formalin 3) Alum adjuvant 4) 2-3 doses 5) Over 95% effective after 1 dose, ~100% after 2 6) Expensive to produce (because of diploid cells, testing for viral inactivation)

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26
Q

Hep E viral family

A

Hepeviridae. Formerly caliciviridae

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27
Q

Hep E virion characteristics 1) 2) 3) 4)

A

1) Non-enveloped, (+)ssRNA virus. 2) Icosahedral. 3) 7.7kb genome 4) Slightly more fragile virion than hep A

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28
Q

Differences between hep A and hep E distribution

A

Both affect Africa, central America, but hep E has a greater burden on Asia

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29
Q

Hep E epidemiology 1) 2) 3)

A

1) Outbreaks associated with faecally-contaminated drinking water. 2) Minimal human-human transmission 3) Closely-related to a virus infecting pigs. Could be a zoonosis.

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30
Q

Hep E incubation period

A

Average 40 days. 2-10 week range

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31
Q

Hep E case fatality rate

A

~1-3% normally. 15-25% in pregnant women

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32
Q

Hep E typical serological course

A

HEP E

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33
Q

Hepatitis viruses that can be sexually-transmitted

A

All, though hep B is the most likely to be transmitted

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34
Q

Hepatitis viruses that can be transmitted through intravenous drug use

A

Hep B and C

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35
Q

Proportion of Australian intravenous drug users who have hep C

A

50-60%

36
Q

Hep B virion structure

A

Enveloped, with hep B surface antigen in envelope Viral DNA within a core (leading to double-walled structure in an electron micrograph) HBsAg can form VLPs

37
Q

Hep B genome 1) 2) 3) 4)

A

1) 3kb relaxed circle of dsDNA 2) Viral polymerase on 5’ end of (-) strand 3) 2 12bp short direct repeats 4) 18nt ssRNA cap on 5’ end of (+) strand

38
Q

HBeAg

A

A variant of the core protein, which has the pre-C region included

39
Q

HBcAg

A

Hep B core protein (missing pre-C region, which would turn it into HBeAg

40
Q

Life cycle of hep B, C, D 1) 2) 3) 4)

A

1) Contact via blood, sexual fluids 2) Virus penetrates intestinal epithelia (does not replicate here like hep A and E do) 3) Enters blood, travels to liver. 4) Replication in hepatocytes

41
Q

Concentrations of hep B virus in body fluids 1) 2) 3)

A

1) High - Blood, serum, wound exudates 2) Moderate - Semen, vaginal fluid, saliva 3) Low - Urine, faeces, sweat, tears, breast milk

42
Q

Role of hep B pre-core

A

Essential for production of replication-competent viruses

43
Q

Perinatial hep B transmission

A

Pregnant women who are HBeAg positive have a much higher risk of transmitting virus to child. Perinatal is the main source of transmission in high-prevalence areas

44
Q

Hep B incubation period

A

Average 60-90 days 45-180 day range

45
Q

Hep B different proportions of clinical jaundice based on age

A

Under 5 years, under 10% develop symptoms Over 5 years, 30-50%

46
Q

Hep B case fatality rate

A

0.5-1%

47
Q

Hep B chronic infection rate

A

Exposure when under 5 years - 30-90% chronic illness Exposure when over 5 years - 2-10%

48
Q

Hep B mortality from chronic liver disease

A

15-25%

49
Q

Two types of cirrhosis

A

Compensated and decompensated. Decompensated leads to death

50
Q

Acute hep B typical serological course

A
51
Q

Chronic hep B typical serological response

A
52
Q

Hep B sequelae 1) 2)

A

1) Immune-mediated liver damage, leading to cirrhosis, maybe primary hepatocellular carcinoma 2) Most-common cause of liver cancer

53
Q

Number of carriers of hep B worldwide

A

500 million

54
Q

Complication of end-stage liver disease

A

Abdominal ascites

55
Q

Proportion of hep B patients that develop hepatocellular carcinoma

A

2-10%

56
Q

Cause of hepatocellular carcinoma

A

Random integration of hep B genome. Repeated destruction and regeneration of hepatocytes can lead to accumulation of chromosomal damage

57
Q

General biomarker for hep B infection

A

HBsAg

58
Q

Biomarker for recovery from hep B, or vaccination

A

anti-HBsAg Ig

59
Q

Marker of acute hep B infection

A

Anti-HBsAg IgM

60
Q

Marker of chronic or past hep B infection

A

Anti-HBsAg IgG

61
Q

Marker of current hep B viral replication

A

HBeAg, hep B DNA

62
Q

Biomarker that indicates that hep B is no longer replicating

A

Anti-HBeAg Ig

63
Q

Hep B vaccine 1) 2) 3)

A

1) Subviral particles purified from yeast 2) Alum adjuvant 3) 2-3 doses

64
Q

Hep D viral family

A

Deltaviridae

65
Q

Hep D characteristics 1) 2) 3)

A

1) 70% complementary ssRNA genome 2) Only encodes a delta protein, which surrounds genome, 3) Requires hep B infection

66
Q

Different ways to be infected with both hep B and D 1) 2)

A

1) Coinfection - Exposure to hep B and D at the same time. Severe acute disease, low risk of chronic infection. 2) Superinfection - Exposure to hep D when already infected with hep C. Usually develop chronic hep D infection. High risk of severe, chronic liver disease

67
Q

Proportion of global population infected with hep C

A

3%

68
Q

Proportion of hep C infections that occur through injecting drug use

A

80%

69
Q

Proportion of hep C patients that develop chronic infection

A

70%

70
Q

Hepatitis virus that can be initially asymptomatic

A

Hep C

71
Q

Can hep C be cleared?

A

Yes. 30% clear the virus

72
Q

Leading indicator for liver transplantation

A

Hep C infection

73
Q

Hepatitis virus without a vaccine

A

Hep C

74
Q

Hep C viral family

A

Flaviviridae

75
Q

Mutation rate of hep C

A

Greater than that of HIV

76
Q

Immunity against hep C

A

Very poor. Carriers can be superinfected with more than one strain of hep C

77
Q

Is hep C culturable?

A

Not until recently. One strain can now be cultured in cells

78
Q

Hep C virion characteristics 1) 2) 3) 4) 5)

A

1) Double lipid membrane 2) E1E2 glycoprotein envelope dimer 3) Capsid 4) +ssRNA genome 5) Cholesterol droplet within envelope

79
Q

Organisation of HCV genome 1) 2) 3) 4)

A

1) 9.4kb genome 2) 5’ UTR IRES 3) 5’ end of genome has structural proteins. 3’ end has nonstructural proteins 4) Encodes a polyprotein

80
Q

HCV RDRP

A

NS5B

81
Q

Receptors used by HCV

A

CD81, SR-BI, , Claudin-1, OCLDN, LDL-R. Complex series of receptors

82
Q

Hep C incubation period

A

Average 6-7 weeks 2-26 week range

83
Q

Proportion of HCV patients that develop jaundice

A

30-40%

84
Q

Proportion of HCV patients that develop chronic hepatitis

A

70%

85
Q

Proportion of hep C patients that are chronic carriers

A

70-90%

86
Q

Hepatitis virus that is hard to resolve using transmission electron microscopy

A

Hep C