Lec 31 Viral Hepatitis Flashcards

1
Q

What is viral hepatitis?

A

inflammation of liver caused by a virus

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2
Q

What are symptoms of viral hepatitis?

A
  • jaundice [yellow skin/eyes]
  • fatigue
  • ab pain
  • loss of appetite
  • nausea
  • vomit
  • diarrhea
  • low fever
  • headache

or may not have symptoms!

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3
Q

What virus/name for hep A?

A

virus: picornavirus
name: infectious hepatitis

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4
Q

What virus/name for hep B?

A

virus: hepadnavirus
name: serum hepatitis

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5
Q

What virus/name for hep C?

A

virus: flaviviridae
name: Non-A, non-B hepatitis

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6
Q

What virus/name for hep d?

A

virus: deltavirus
name: delta agent

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7
Q

What virus/name for hep E?

A

virus: hepevirus
name: enteric non-A, non-B hepatitis

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8
Q

What are similarities between the Hepatitis viruses?

A
  • similar symptoms
  • liver tropism and infect hepatocytes
  • primary/exclusively associated with liver disease
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9
Q

Hep A: onset, severity, chronicity?

A

onset: abrupt
severity: mild
chronic: no

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10
Q

Hep B: onset, severity, chronicity?

A

onset: slow
severity: occasionally severe
chronic: yes

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11
Q

Hep C: onset, severity, chronicity?

A

onset: slow
severity: usually subclinical
chronic: yes

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12
Q

Hep d: onset, severity, chronicity?

A

onset: abrupt
severity: occasionally severe
chronic: yes

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13
Q

Hep E: onset, severity, chronicity?

A

onset: abrupt
severity: severe in pregnant
chronic: no

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14
Q

Hep A: Is there a vaccine? treatment?

A

vaccine: children > 1 yr, travelers, at risk
treat: none

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15
Q

Hep B: Is there a vaccine? treatment?

A

vaccine: for infants and adults at risk
treat: yes, rarely cures

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16
Q

Hep C: Is there a vaccine? treatment?

A

vaccine: none
treat: yes

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17
Q

Hep d: Is there a vaccine? treatment?

A

vaccine: none
treat: none

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18
Q

Hep E: Is there a vaccine? treatment?

A

vaccine: none
treat: none

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19
Q

Who gets Hep B?

A
  • common in high risk groups –> IV drug users
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20
Q

What are viral characteristics of HBV [including family + genus]?

A

family: hepadnaviridae
genus: orthohepadnavirus
- spherical particle
- enveloped
- partially double stranded
- circular DNA
- small genome

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21
Q

How does replication of HBV occur?

A

via RNA intermediate by reverse transcription

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22
Q

What are possible outcomes of acute HBV infection?

A

if have effective T cell response: get subclinical disease or acute hepatitis and then recover [<1% get fulminant hepatitis and die]

if limited T cell response: get persistant infection leading to recovery or chronic hepatitis and then cirrhosis

– limited response more likely in perinatally infected infants and immunocompromised

23
Q

What is immune response to acut hep B? How does this differ in chronic Heb B

A
  • production anti-HBsAg, anti-HBeAg, anti-HBc-Ag

- in chronic hep B no anti-HBs

24
Q

What are levels of anti-HBc Igm, Anti-HBc IgG, HBsAg, and Anti-HBs in resolved acute HBV?

A

anti HBc IgM: negative
anti HBc IgG: pos
HBsAg: neg
Anti-HBs: pos

25
What are levels of anti-HBc Igm, Anti-HBc IgG, HBsAg, and Anti-HBs in chronic HBV?
anti HBc IgM: neg anti HBc IgG: pos HBsAg: pos Anti-HBs: neg
26
What is virus theory of mech for induction of hepatocellular carcinoma?
- viral products act as oncogenes | - get integration of viral genome and disruption of cellular gene expression
27
What is indirect/nodular cirrhosis theory of mech for induction of hepatocellular carcinoma?
- chronic hepatic injury and repair processes lead to genetic changes causing uncontrolled growth
28
What are the 2 treatments for chronic HBV?
- pegylated interferon alpha = antiviral cytokine | - reverse transcriptase inhibitors [almivudine, entecavir, tenofovir]
29
Who do you treat for chornic HBV?
- pts positive for HBsAg for > 6 mos - high HBV DNA levels - high ALT - evidence of liver disease
30
What is mech of lamivudine? administration? resistance? cost?
mech: nucleoside analog reverse transcriptase inhibitor, similar to deoxyC, terminates chain admin: oral resistance: high levels cost: low
31
What is mech of entecavir? administration? resistance? cost?
mech: nucleoside analog reverse transcriptase inhibitor, similar to deoxyG, terminates chain admin: oral resistance: low levels, cross-resistant with lamivudine cost: high
32
What is mech of tenofovir? administration? resistance? cost?
mech: nucleoside analog reverse transcriptase inhibitor, similar to deoxyA, terminates chain admin: oral resistance: none, use in pts with lamivudine or entecavir resistance cost: intermediate
33
What are vaccines for HBV?
- early ones used HBsAg - current uses non-glycosylated HBsAg in yeast and adjuvant alum - requires multiple immunization, failure common in HIV - can give along with hep B Ig in neonates born to infected mothers just after birth to prevent infection
34
What is hep delta virus? who gets it? symptoms?
- subviral satellite virus --> needs HBV to provide envelope proteins for assembly - only infects HBV+ - increases incidence of active hepatitis, cirrhosis, hepatocellular carcinoma in chronic HBV and likelihood of death from fulminant hep
35
What are top sources of HCV infection?
- IV drug use - sexual - transfusion
36
What are viral properties of HCV including family/genus?
family: flaviviridae genus: hepacivirus - single strand - pos sense RNA - high mutation rate [error-prone RNA pol] - exists to quasispecies
37
What is significance of HCV as a quasispecies?
- allows to escape from immune response | - often resistant to treatment
38
What are outcomes of HCV infection?
acute --> 80% get chronic - -> 35% get stable chronic - -> 65% slowly progressive with some symptoms --> leads to cirrhosis in 30% --> can get slowly progressive cirrhosis or liver failure/cancer/death
39
What is mech of ineffective cellular immune response to HCV?
- co infection with HIV - viral evasion of innate immune response - impaired NK cell, dendritic cell function - glycosylated envelope proteins protect against Ab mediated neutralization - sequence variations allows immune escape for T & B cell
40
How do you diagnose/assess HCV infection?
- serology: look for antibodies to core, NS3 and NS5 detected within 6-8 wks of exposure - RT-PCR: measure viral load in serum, genotype via sequence - liver biopsy: assess stage of liver injury
41
how do you treat HCV?
indirect antivral: - PEG-interferon-alpha + ribavirin direct acting - telaprevir/bocoprevir [protease inhibitors] + PEG-IFN-a + ribavirin - sofusbuvir [polymerase inhibit] - simepravir [protease inhibit]
42
What are downsides of telpravir/bocoprevir as treatment for HCV?
- only targets genotype 1 | - get anemia, rash, interforon still need, 8 hr dosing
43
What are downsides of sofubuvir as treatment for HCV?
- no side effects | - interacts with P-glycoprotein substrate, avoid P-gp inducers [rifampin, st johns wort]
44
What are downsides of simepravir as treatment for HCV?
side effect: photosensitivity/rash | drug interactions: CYP3A4 inducers/inhibitors
45
How is Hep A transmitted?
person to person via fecal-oral route
46
What are clinical features of hep A [time frame, complications]
- self limited [3 wks] | - can profress to fulminant hep failure in pts with underlying liver diesase [HBV or HCV]
47
How do you diagnose HAV?
- symptoms of acute viral hepatitis | - detection of HAV-specific IgM anitbody in acute-phase serum
48
What is treatment for HAV?
supportive
49
How do you prevent HAV?
vaccination [recommend at under 1 yr old]
50
What is typical course of acute hep A?
- jaundice symptoms coincide with peak ALT, then ALT lower, IgM Anti-HAV lowers, Anti-HAV stays high
51
What is clinical presentation of Hep E? Who gets it?
- similar clinical to HAV - found in developing countries with fecal contamination of drinking water - self limited followed by recovery - chronic infection does not occur - occassionaly get fulminant hep in pregnant women
52
How is hep E transmitted?
fecal oral = fecal contamination of drinking water in developing countries
53
What does it mean if you have negative Anit-HBc IgM, anti-HBc IgG, and HBsAg by positive Anti-HBs for HBV?
means you were not infected but had a prior acute vaccination for HBV