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Medical Microbiology and Virology > Viral hepatitis > Flashcards

Viral hepatitis Flashcards

1
Q

When over half the liver is destroyed, function begins to fail, and you may see jaundice as first sign, as bilirubin cannot be transported into bile. Hepatitis can lead to cirrhosis

What virus families do these viruses belong to?

HAV

HBV

HCV

A

HAV - hepatovirus

HBV - hepadnavirus

HCV - flavivirus

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2
Q

What virus families do these viruses belong to?

HDV

HEV

Yellow fever

A

HDV - deltavirus. Required HBV co-infection, as incompelte virus

HEV - orthohepevirus

Yellow fever - flavivirus

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3
Q

Which hepatitis viruses are:

  • ssRNA
  • dsDNA
A 
HAV
HCV
HDV
HEV
YF

HBV

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4
Q

Which hepatitis viruses are transmitted -

  • faecal-oral
  • blood-borne
  • mosquito
A
  • faecal-oral - HAV/HEV
  • blood-borne - HBV/ HCV/ HDV
  • mosquito - YF
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5
Q

What are other rarer viral causes of hepatitis?

A

Adenovirus
CMV
EBV
HSV

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6
Q

Which viruses are most associated with cirrhosis and progression to HCC?

A

HBV

HCV

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7
Q

HAV only has one serotype, and is endemic worldwide. 90% of children have been infected by age 5

What is transmission route?

What is incubation period?

A

Faecal-oral - poor hygiene/ anal itnercourse

4 weeks
Virus present in stool before symptoms appear
Outbreaks occur in schools/ camps, and near sources of contaminated water. Military will be vaccinated

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8
Q

What is life cycle of HAV?

A

Ingested in GI tract
Moves to bloodstream - replicates
Enters hepatocytes
Virions excreted into small intestine - appear in faeces

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9
Q

What are symptoms of HAV?

A

Nausea
Diarrhoea
Fever
Jaundice - more common in adults not previously infected

Has most sudden onset of viral hepatitis viruses

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10
Q

What is management of HAV?

A

Symptomatic
Vaccinate
Occasionally pooled human normal immunoglobulin

Avoid work/ school for 7 days as potentially infectious

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11
Q

How to diagnose HAV infection?

A

HAV IgM

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12
Q

HAV

Which at risk groups require vaccination?

A 
Travellers
Sewage workers
Child day-care
MSM
IVDU
Haemophilia
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13
Q

HEV spreads via faecal-oral route.

Which countries is it more commonly seen in?

A

From East Africa/ middle east/ Asia

Mexico

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14
Q

How many genotypes of HEV are there?

A

Genotypes 1/2 - large outbreaks in resource poor countries. Usually contaminated drinking water

Genotypes 3/4 - developing and developed countries. Usually food borne - undercooked food

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15
Q

What are natural reservoirs for HAV?

A 
Chickens
Pigs
Rabbits
Boar
Dear

Mostly all asymptomatic

Usually transmitted faecal-oral between humans
But can originate in animals from undercooked pork

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16
Q

HEV infection

What are symptoms?

Which groups need to be wary?

A

Usually self-limiting mild illness

Pregnancy - may be severe, with up to 20% mortality

Immunosuppressed - 50% becomes chronic infection

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17
Q

How is HEV diagnosed?

Treatment is supportive. Vaccine in development

A

HEV IgM/ IgG

HEV RNA in blood/ stool

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18
Q

HBV is partially dsDNA virus. Estimated 350million carriers worldwide. Complete HBV virion known as Dane particle.

What are the characteristics of the HBV antigens and antibodies?

HBsAg

HBsAb

A

HBsAg - envelope antigen of HBV particle, can also occur as free particle in the blood. Indicates infectivity in blood. Part of antigen used to create vaccine

HBsAb - antibody response to HBsAg. Indicates post-vaccination response, and after resolved HBV infection

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19
Q

What are the characteristics of the HBV antigens and antibodies?

HBcAb (total)

HBc IgM

A

HBcAb - antibody to HB core antigen. Appears early in infection. Includes HBc IgM. Persists for life

HBc IgM - appears in acute HBV infection. Can last for 3 months. Is marker of acute HBV infection (in past 6 months). Can also be seen in those with HBeAg carriers with high viral replication

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20
Q

What are the characteristics of the HBV antigens and antibodies?

HBeAg

HBeAb

A

HBeAg - antigen derived from HBc. Indicates high transmissibility as indicates high replication and infectivity. It is soluble component secreted by virus core, also expressed on hepatocyte surface as target for host immune response

HBeAb - antibody to HBV core (includes HBeAG/ HBc). This occurs when HBeAg reduces, and is a sign of low-infectivity. HBeAg seroconversion when this antibody produced

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21
Q

What is route of transmission of HBV?

A

Vertical
Sexual
Blood products/ needles/ dialysis equipment
Tattoo/ accupuncture

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22
Q

How many genotypes are there of HBV?

A

10 A-J

ADG UK

Over 40 sub-genotypes

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23
Q

What is incubation period of HBV?

A

6 weeks - 6 months

Median is 2.5 months

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24
Q

HBV infeciton - how does liver damage occur?

A

Virus does not cause direct damage. Immune mediated damage of hepatocytes.

Virus-specific cytotoxic T-cells attack hepatocytes

As damage increases, signs of hepatitis appear

Immune response slowly becomes effective over period of months, so blood is no longer infectious. But virus remains in liver

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25
Q

Healthy adults with vigorous immune response can clear virus rapidly, but suffer severe illness. 10% cannot clear, and become carriers

What is definition of HBV carrier?

Who is at risk of become chronic carrier HBV?

A

Detection of HBsAg in blood 6 months after exposure

Immunodeficient - likely to be carrier, but wont suffer much disease

If infected perinatally, have 95% carriage rate

Males more likely to be carrier

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26
Q

What are complications of HBV?

A

Cirrhosis

HCC - 20-30 years following initial infection

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27
Q

HBeAg is used as marker of infectivity. What other tests help identify infectivity?

A

HBV DNA load become useful marker, as some virus strains have mutations in e antigen, which results in absence of HBeAg, although viable virion produced. Known as pre-core mutant virus

This therefore means they can be HBeAg neg, and HBeAb positive but could be highly infectious.

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28
Q

What are expected test results in the following conditions?

Acute Hepatitis B

HBsAg
HB core antibody (total anti-HBc)
HB core IgM (anti-HBcIgM)
HBeAb (anti-HBe)
HBeAg
HB surface antibody (anti-HBs)
A

Acute Hepatitis B

HBsAg - pos
HB core antibody (total anti-HBc) - pos 
HB core IgM (anti-HBcIgM) - pos
HBeAb - neg
HBeAg - pos
HB surface antibody (anti-HBs) - neg

HBsAg appears in serum during incubation period.

If self-limiting, HBsAg will gradually reduce as HB core IgM is produced. HB core IgM then reduces and is replaced with HB core IgG

If persisting infection, HBsAG remains high. HBeAg begins to icnrease. HB core antibodies are produced, IgM reduces, and is replaced by IgG. But this is ineffective at clearing the virus

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29
Q

What are expected test results in the following conditions?

Past Hepatitis B

HBsAg
HB core antibody (total anti-HBc)
HB core IgM (anti-HBcIgM)
HBeAb (anti-HBe)
HBeAg
HB surface antibody (anti-HBs)
A

Past Hepatitis B

HBsAg - neg
HB core antibody (total anti-HBc) - pos 
HB core IgM (anti-HBcIgM) - neg
HBeAb - pos
HBeAg - neg
HB surface antibody (anti-HBs) - pos
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30
Q

What are expected test results in the following conditions?

Hepatitis B carrier low/ high infectivity

HBsAg
HB core antibody (total anti-HBc)
HB core IgM (anti-HBcIgM)
HBeAb (anti-HBe)
HBeAg
HB surface antibody (anti-HBs)
A

Hepatitis B carrier high infectivity

HBsAg - pos
HB core antibody (total anti-HBc) - pos 
HB core IgM (anti-HBcIgM) - neg
HBeAb - neg
HBeAg - pos
HB surface antibody (anti-HBs) - neg

Hepatitis B carrier low infectivity

HBsAg - pos
HB core antibody (total anti-HBc) - pos 
HB core IgM (anti-HBcIgM) - neg
HBeAb - pos
HBeAg - neg
HB surface antibody (anti-HBs) - neg

anti-HBs only turns positive upon vaccination, or after approx 36 weeks after infection

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31
Q

What are expected test results in the following conditions?

Hepatitis vaccine response

HBsAg
HB core antibody (total anti-HBc)
HB core IgM (anti-HBcIgM)
HBeAb (anti-HBe)
HBeAg
HB surface antibody (anti-HBs)
A

Hepatitis vaccine response

HBsAg - neg
HB core antibody (total anti-HBc) - neg 
HB core IgM (anti-HBcIgM) - neg
HBeAb - neg
HBeAg - neg
HB surface antibody (anti-HBs) - pos
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32
Q

HBV vaccine gives good protection to 90% of people. 10% will not produce protective HB surface antibody.

How many doses are required?

Who is recommended to be vaccinated?

A

Three injections over 6 months
0, 1, 6 months - routine
0, 1, 2 months - accelerated

Healthcare workers
IVDU
Transfusion dependent
Dialysis patient
Sex worker

Now all neonates recommended to be vaccinated

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33
Q

If unvaccinated has needlestick injury, what treatment can be given?

A

Give HepB vaccination -

  • if already immunised - give booster dose
  • if not previously immunised - accelerated course 3 injections 3 months
  • if vaccine non-responder - boost dose an HBIG

Consider HBIG

Check green book - depends on vaccine status of recipient, and risk form source

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34
Q

What is structure of HBV virion?

not DNA genes

A 
DNA 
DNA polymerase
HBcAg
HBsAg with glycoproteins
Envelope
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35
Q

What is structure of HBV DNA?

A

All 10 genotypes (A-J) all contain four long open reading frames (ORFs)

C - core. Encodes HBcAg and HBeAg. Mutations in pre-core region result in lack of HBeAG

S - surface. Encodes pre-S1/ pre-S2/ s region - encode HBsAG

P - polymerase. Encodes DNA polymerase and ribonuclease H. Encompasses 75% of whole genome. Also responsible for reverse transcription.

X gene - encodes polypeptide with several functions

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36
Q

What are possibilities for following serology results HBV?

HBsAg - negative
anti-HBc - positive
anti-HBs - negative

A
  1. False-positive anti-HBc, thus susceptible

2 Resolved infection (most common) - not devleoped anti-HBs yet

  1. “Low level” chronic infection
  2. passive transfer of maternal anti-HBc – in children up to 3 years of age
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37
Q

What are phases 1-3 (5) of HBV infection?

The progression through these phases of chronic HBV infection can be accompanied by the development of hepatic fibrosis, cirrhosis and HCC formation

Phases related to HBeAg/ HBV DNA levels

A

Phase 1 - high replicative, low inflammatory state. HBeAg positivity, high viral load, normal aminotransferases

Phase 2 - HBeAg positive chronic hepatitis B phase, fluctuating aminotransferases, high HBV DNA, inflammation on liver biopsy

Phase 3 - HBeAg negative phase, low levels HBV DNA, and normal aminotransferases. If persists, has lower rate of progression towards cirrhosis

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38
Q

What are phases 4-5 (5) of HBV infection?

The progression through these phases of chronic HBV infection can be accompanied by the development of hepatic fibrosis, cirrhosis and HCC formation

A

Phase 4 - HBeAg negative, representing late immune reactive phase, with periodic fluctuating levels of aminotransferases and HBV DNA. Virus may have nucleotide substitutions in pre-core or basal core promoter region, explaining lack of HBeAg

Phase 5 - HBSag negative phase, HBV DNA usually undetectable

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39
Q

What are advantages of genotyping HBV?

A

Can locate origin - different genotypes more prevalent certain regions

Tailor treatment to patient

Certain genotypes have different modes of transmission e.g vertical/ horizontal, useful for epidemiology

Genotype influences disease outcomes and development of HCC

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40
Q

Mutation in error prone HBV polymerase creates genetic variability, termed genotype.

What are potential benefits of mutations?

A

Antiviral drug resistance mutations

Antiviral drug-associated potential vaccine escape mutants

Immune escape mutants - evade B cells

Deletion mutants unable to express non-essential HBV proteins e.g HBeAg

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41
Q

Where are most common HBV genotypes found geogrpahically?

A

genotype A found in North America, Europe, South-East Africa and India;

genotypes B and C in Asia and Oceania;

genotype D, the most widespread, in North America, North Africa, Europe, the Middle-East and Oceania;

genotype E in West Africa;

genotype F in South America;

genotypes G and H in Central and South America

UK - ADG

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42
Q

Which HBV genotypes are transmitted vertically?

Which HBV genotypes are transmitted horizontally?

A

Vertical -
A2
B
C

Horizontal -
A1
D
E
F
G
H
I
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43
Q

Which HBV genotypes are more likely to be HBeAg positive?

A

A2 - early seroconversion

C - late seroconversion

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44
Q

Which HBV genotypes are at higher risk of developing cirrhosis/ HCC?

A

A1
C
D
F

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45
Q

Which HBV genotypes are more responsive to IFN-alpha?

A

A1

B

46
Q

Apart from HBV serology, what are initial tests for someone presenting with suspected HepB?

Do not check initial HBV genotype. Treat first, and if fails, check genotype

A

HAV Ab
HCV DNA/ Ab
HIV Ab

STIs
Chlamdyia
Gonorrhoea
Syphilis

FBC
U+Es
LFTs
Coag
AFP

USS liver/ fibroscan

47
Q

HBeAg negative chronic HBV, compensated liver disease. What are treatment options?

Wait until it is chronic, as 90% will clear spontaneously

A
  • initial 48-week course of peginterferon alfa-2a as first-line treatment (cannot be continued past this date. So if treatment to continue e.g lifelong, switch to other agent
  • Offer entecavir or tenofovir disoproxil as second-line treatment to people with detectable
    HBV DNA after first-line treatment with peginterferon alfa-2a.
48
Q

HBeAg positive chronic HBV, compensated liver disease. What are treatment options?

A
  • initial 48-week course of peginterferon alfa-2a as first-line treatment. NICE guidelines. Other countries suggest straight to tenofovir/ entecavir
  • tenofovir disoproxil as second-line treatment to people who do not undergo HBeAg seroconversion or who relapse (revert to being HBeAg positive following seroconversion) after first-line treatment with peginterferon alfa-2a.
  • entecavir as an alternative second-line treatment to people who cannot tolerate
    tenofovir disoproxil or if it is contraindicated.
49
Q

Woman diagnosed HBv positive during pregnancy/ breast feeding. What are treatment options?

A

tenofovir disoproxil in the third trimester to reduce the risk of transmission of HBV to the baby

Avoid peginterferon alfa-2a in pregnancy. Must use contraception if on treatment and not pregnant

50
Q

What is mechanism of action of:

peginterferon alfa-2a

A

immunomodulatory - acts by binding to human type 1 interferon receptors. Activation and dimerization of this receptor induces the body’s innate antiviral response by activating the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway

51
Q

what is mechanism of action of:

tenofovir

entecavir

A

tenofovir - NRTI - selectively inhibits viral reverse transcriptase by causing DNA chain termination

entecavir - NRTI - guanosine analgoue, cause DNA chain termination

52
Q

What is treatment for HBV decompensated liver disease?

A
  • Refer hepatology/ transplant
  • pegylated interferon contraindicated
  • entecavir first line (if no history lamivudine resistance)
  • tenofovir second line (if history lamivudine resistance)
53
Q

Fibroscan can be used to monitor liver stiffness, as marker of cirrhosis. It assesses large area of liver, so may give better idea of cirrhosis, than liver biopsy

What results indicated liver stiffness measurement (LSM):
Mild
Severe
Cirrhosis

Beware liver elasticity can be influenced by obesity (fatty liver) or alcohol use

A

Mild - 2.5 -7.5 kPa

Severe - 7.5 - 12.4 kPa

Cirrhosis - >12.5 kPa

Treatment usually initiated if LSM >11.0 kPa. If above 11, this is highly suggestive of cirrhosis, and USS is not required.

If between 6-11, cirrhosis cannot be determined. So biopsy may be required.

54
Q

Who should be initiated on treatment for HBV?

A
  1. Any patient with cirrhosis - regardless of HBV DNA/ ALT levels
  2. adults aged 30 years and older -
    - HBV DNA >2000 IU/ml
    - ALT >30 male, >19 female on 2 consecutive tests, conducted 3 months apart
  3. adults younger than 30 years -
    - HBV DNA >2000 IU/ml
    - ALT >30 male, >19 female on 2 consecutive tests, conducted 3 months apart
    - must have necroinflammation or fibrosis on liver biopsy or a transient elastography score greater than 6 kPa.
    - if HBV DNA >20 000 treat irregardless
55
Q

Initial treatment of HBV is peginterferon alfa-2a for 48 weeks.

HBV serology should be checked at 24 weeks. If not improving, what should be done?

A

Review adherence to treatment

Stop treatment if -

  • If HBV DNA level has decreased by less than 2 log10 IU/ml or
  • HBsAg is greater than 20,000 IU/ml or
  • If do not udnergo HBeAg seroconversion/ relapse

Offer tenofovir second line therapy

Offer entecavir alternative second line if tenofovir not tolerated/ contra-indicated

56
Q

After completing 48 weeks of treatment for HBV, when can anti-virals been stopped?

A

No cirrhosis
- stop after 12 months after achieving undetectable HBV DNA and HBsAg seroconversion

Cirrhosis
- Do not stop treatment after achieving undetecable HBV DNA and HBsAg seroconversion

57
Q

How is HBV managed in pregnancy? Mother/ baby

A

Mother -

  • tenofovir in third trimester to reduce risk transmission to baby
  • stop treatment 4-12 weeks after birth, unless meets criteria for long term treatment
  • no risk transmitting via breast milk. Can breast feed on anti-virals

Baby -

  • HepB immunisation
  • HBIG
58
Q

What is treatment if HBV/HCV co-infected?

A

peginterferon alfa and ribavirin

59
Q

What is treatment for HBV/ HDV co-infection?

A

48-week course of peginterferon alfa-2a if evidence significant fibrosis

Stop treatment after HBsAg seroconversion.

60
Q

Some patients may be HBsAg positive, but not meet criteria for treatment. If they begin immunomodulating therapy for AI/ atopic disease, there is risk of full HepB infection.

What prophylaxis should be offered?

HBV DNA >2000 IU/ml

HBV DNA < 2000 IU/ml

A

HBV DNA >2000 IU/ml -
- entecavir or tenofovir

HBV DNA < 2000 IU/ml

  • lamivudine if treatment lasting <6 months
  • entecavir or tenofovir if treatment lasting >6 months

Start prophylaxis before beginning immunosuppressive therapy and continue for a
minimum of 6 months after HBeAg seroconversion and HBV DNA is undetectable

61
Q

HBsAg negative
anti-HBc positive

Patient starting immunotherapy for <6 months. What prophylaxis should be offered?

A

lamivudine

start prophylaxis before beginning immunosuppressive therapy and continue for a minimum of 6 months after stopping immunosuppressive therapy.

62
Q

HBsAg negative
anti-HBc positive
anti-HBs negative

Patient is not starting immunotherapy.

What treatment should be offered?

A

monitor HBV DNA monthly and offer prophylaxis (lamivudine) to people whose HBV DNA becomes detectable

63
Q

HBsAg negative
anti-HBc positive
anti-HBs positive

Patient not starting immunotherapy.

What treatment should be offered?

A

Do not offer prophylaxis

64
Q

Monitoring patients with HBV not on treatment.

how often should LFTs be checked?

A
  • immune-tolerant phase (defined by active viral replication and normal ALT levels [less than 30 IU/L in males and less than 19 IU/L in females]). Check every 24 weeks. Check every 12 weeks if rise in ALT
  • chronic hepatitis B infection (defined as HBeAg negative on 2 consecutive tests with normal ALT [less than 30 IU/L in males and less than 19 IU/L in females] and HBV DNA less than 2000 IU/ml). Check every 48 weeks
65
Q

HBV infection, patient has HBeAg seroconversion (produces antibodies to HBeAg)

When should bloods be monitored?

A

Weeks 4, 12, 24

66
Q

HBV infected patient, when do bloods need checked in following patients

entecavir
lamivudine
tenofovir

A

Routine bloods -
week 4
then every 3 months

HBV serology -
week 12
week 24
week 48

67
Q

In patients with significant fibrosis due to HBV, how often should be monitored for HCC?

A

Significant fibrosis -
every 6 months with USS/ AFP

no fibrosis -

  • if HBV DNA >20 000 - consider USS
  • if HBV low, no follow up
68
Q

Why is HBeAg seroconversion an important marker?

A

In HBeAg-positive disease, HBeAg seroconversion is a predictor of durable response to antiviral
treatment and can be used as a milestone after which treatment can be stopped

no marker exists for HBeAg negative disease

69
Q

What are infective causes of acute hepatitis?

A

Hep A-E
CMV
EBV
HSV

Brucellosis
Leptospirosis

70
Q

What general advice should be given to someone with acute hepB infection?

Advice for close contacts

A

HAV vaccination

Avoid sexual intercourse

Avoid alcohol

Avoid sharing razors

HepB vaccination close contacts

Contact trace

71
Q

When to stop treatment for HBV?

A
  • HBeAg seroconversion, and HBV DNA undetectable - continue treatment for 12 months after this point.
  • 50% seroconvert by 5 years
  • If HBeAG negative - continuee lifelong treatment to prevent cirrhosis/ HCC
72
Q

Hepatitis D has small single stranded RNA genome. It is defective virus, and can only multiply in HBV co-infected cell.

What is structure of HDV?

A

HDV single stranded RNA
HDV Ag
HBsAg acquired when buds from hepatocyte

Once inside hepatocyte, uses host RNA polymerases to replicate

73
Q

How is HDV infection diagnosed?

A

HDV antigen
HDV IgM/IgG
HBsAg

74
Q

What is treatment for HDV infection?

A

Treat as HBV guidelines

HBV vaccination is reducing incidence of HDV

75
Q

HepC is +ss RNA virus in hepcivirus genus in falvivididae family. Estimated 185 million worldwide infected

What is transmission route?

A

Blood
Needles
Tatto/ piercing/ accupuncutre
Dialysis

Uncommon vertical transmission

76
Q

HCV has six major genotypes, and more than 100 subtypes, due to high error rate in RNA replication by NS5b polymerase.

Which genotypes are prevalent in different geographical distributions?

A

90% of infections in Europe are genotype 1, 2, 3
(1 + 3 most common)

Americas - genotype 1/2

Northeast/central Africa - genotype 4

Asia - genotype 6

77
Q

What is significance of HCV genotype?

A

Predictive of antiviral therapy response

Genotype 1 associated with poor response

Being infected with one genotype does not protect against other. Therefore making vaccine more difficult

78
Q

How many HCV infected people developed chronic HCV?

What is incubation period?

A

80% become chronically infected
20% spontaenosuly clear virus by 6 months (90% in HBV)

2-4 months. Mean 7 weeks

79
Q

What are symptoms of HCV infection?

A

Most have subclinical infection

25% develop jaundice, as opposed to 90% seen in acute HBV infection

80
Q

what percentage spontaneously clear HCV?

What percent of those with chronic HCV go on to develop cirrhosis/ HCC?

A

25% spontaneously clear (90% in HBV)

80% HCV infected will develop cirrhosis

10% will progress to HCC

81
Q

What tests are used for HCV?

A

HCV RNA - shows if current infection

HCV Ab - shows if ever had infection or current infection

82
Q

The goal of treatment is to eradicate the virus, achieve a sustained virological response (SVR), and prevent disease progression

SVR - undetectable HCV RNA in the blood 12 weeks after treatment completion is considered equivalent to a cure

All patients with HCV are eligible for treatment (regardless of fibrosis status). Treatment is Direct Acting Antivirals (DAA)

How long is treatment for?

A

Initial tests same as HBV

8 - 12 weeks treatment which costs approx £40 000

90% will be cured by end of treatment

83
Q

What does choice of HCV treatment depend on?

A

Genotype
Liver disease - Child-Pugh score

If HCV viral load dose not reduce by 4 weeks, then spontaneous clearance unlikely. Consider starting treatment

HCV can become resistant to anti-virals. On stopping treatment this reverses backto “wild-type”. Restarting treatment does not trigger resistance again, because RNA virus cannot store resistance genes

84
Q

HCV treatment

Non-cirrhotic

Genotype -
1a
1b
2
3
4
5/6
A

1a sofosbuvir + ledipasvir (8-12 weeks)

1b sofosbuvir + ledipasvir (8-12 weeks)

2 sofosbuvir + ledipasvir

3 sofosbuvir + ledipasvir

4 grazoprevir plus elbasivir

5/6 sofosbuvir + ledipasvir

85
Q

HCV treatment

Compensated cirrhosis

Genotype -
1a
1b
2
3
4
5/6
A

1a sofosbuvir + ledipasvir

1b sofosbuvir + ledipasvir

2 sofosbuvir + ledipasvir

3 sofosbuvir + ledipasvir

4 grazoprevir plus elbasivir

5/6 sofosbuvir + ledipasvir

Difference from non-cirrhotic, is all must be 12 weeks treatment

86
Q

HCV treatment

Decompensated cirrhosis

Genotype -
1a
1b
2
3
4
A

1a sofosbuvir + ledipasvir + ribavirin

1b sofosbuvir + velpatasvir + ribavirin

2 sofosbuvir + velpatasvir + ribavirin

3 sofosbuvir + velpatasvir + ribavirin

4 grazoprevir + elbasvir + ribavirin

All for 12 weeks

Primary treatment is liver transplant, so should be managed by gastroenterologist

87
Q

What are four clases of DAA drugs for HCV?

A

NS3/4A PI

NS5A inhibitor

Nucleotide/ nucleoside NS5B polymerase inhibitor

Non-nucleoside NS5B polymerase inhibitor

88
Q

Mechanism of action of DAA HCV

NS3/4A PI

Examples

A

Binds to viral protease inhibiting it
Grazoprevir
Simeprivir

89
Q

Mechanism of action of DAA HCV

NS5A inhibitor

Examples

A

Blocks NS5A virus protein required for replication

Elbasvir
Ledipasvir
Velpatasvir

90
Q

Mechanism of action of DAA HCV

Nucleotide/ nucleoside NS5B polymerase inhibitor

Examples

A

Prevents HCV replication in hepatocyte

Sofosbuvir

91
Q

Mechanism of action of DAA HCV

Non-nucleoside NS5B polymerase inhibitor

Examples

A

Binds to polymerase preventing further viral replication

Dasabuvir

92
Q

What are most common side effects of DAA HCV?

A

Fatigue - anaemia
GI symptoms
Headache
Insomnia

93
Q

HCV treatment, when is HCV RNA levels monitored?

A

Weeks 2, 4, 8, 12

Assess for SVR - absence of HCV RNA by PCR at 6 months on completing treatment

An increase in viral load from on-treatment nadir of greater than 1 log is indicative of poor adherence and virological breakthrough and treatment will be discontinued. Discontinuation avoids futile therapy
and minimises the development of drug resistance.

94
Q

HCV +ssRNA virus

RNA contains 10 proteins, what are they?

A

C - core protein
E1/E2 - envelope proteins
NS2a - envelope protein
NS2, NS3, NS4a, NS4b, NS5a, NS5b -non-structural

95
Q

What are extraheptaic manifestations of HCV infection?

A 
lichen planus
Mixed cryoglobulinaemia
Membranoproliferative glomerulonephritis
porphyia cutanea tarda
pulmonary fibrosis
Sjogren's syndrome
Thyroid disease
96
Q

HCV initial investigations before starting treatment

A

HCV Ab - detectable after 6 weeks (HIV may have false-negative result)

HCV RNA - detectable after few days

Genotype testing

Fibroscan/ USS or liver biopsy

97
Q

HIV HCV co-infection is associated with faster progression towards cirrhosis.

Must start/ continue HIV ART.

When would you not start HCV DAA?

A

CD4 count less than 200 cells/mm3, it may be advisable to first initiate antiretroviral therapy and defer HCV therapy until the person is stable on antiretroviral therapy with suppressed HIV RNA levels

Most clinical trials evaluating the efficacy of HCV therapy in persons with HIV have enrolled those with suppressed HIV RNA levels and CD4 counts greater than 200 cells/mm3.

ART will slow HCV progresison towards liver cirrhosis

98
Q

HIV/ HCV co-infection

What aspects should be considered about drug therapy?

A

If treatment for both HIV and HCV is indicated, the selected treatment regimens should consider potential drug interactions and whether the recommended duration for persons with HCV monoinfection should be given for a longer duration because of the confection with HIV.

LFTs may raise substantially more if co-infected, and may be attributed to immune reconstitution inflammatory syndrome

99
Q

Monitoring hepatotoxicity on DAA for HCV.

Up to what level of transaminases is safe?

A

5x upper limit of normal

However, if develops rising bilirubin, and symptoms such as nausea, weakness. Need to evaluate treatment/ other causes e.g HBV, alcohol,

If blood tests show raised LFTs, then perform more frequent monitoring

100
Q

HIV/ HCV co-infection

Which ART drugs are contra-indicated?

NRTI

NNRTI

INSTI

PI

CCR5

A

NRTIs: avoid tenofovir + sofosbuvir

NNRTIs: avoid efavirenz and etravirine

INSTIs: avoid with tenofovir

PIs - avoid all

CCR5 - maraviroc safe

101
Q

All blood and organ donors need to be screened for infection to prevent transmission

Which tests are performed?

A

HIV Ag/Ab, RNA

HBsAg, HBV DNA

HCV Ab, HCV RNA

HTLV Ab

CMV IgG

EBV VCA (viral capsid antigen) IgG - only organ donor

Treponema pallidum Ab

Toxoplasma IgG - only organ donor

Travel histroy dependent:
West Nile Virus
Trypanosoma cruzi IgG
Malarial Ab

Individuals who receive blood products, particularly pooled blood products, could have false positive serology tests due to passively acquired antibodies from donor

102
Q

How to reduce risk of sharp injuries/ BBV exposure?

A

Treat ever patient as potentially infectious

Training on how to deal with sharps

Sharps bins

Gloves

Mask/ eye shield if splash exposure

Vaccinate HBV

103
Q

Healthcare worker with HIV.

What are they allowed to do at work?

A

If viral load >200 copies/ ml, not allowed to practice exposure prone procedures

104
Q

Healthcare worker with HBV

What are they allowed to do at work?

A

HBeAg positive - cannot practice exposure prone procedures

HBeAg negative - if HBV DNA >1000 genome copies/ml

HBeAg negative - if HBV DNA <1000 genome copies/ml can return to exposure prone procedures

HCV - RNA undetectable
HIV - RNA <200 copies

105
Q

Healthcare worker with HCV

What are they allowed to do at work?

A

Not allowed exposure prone procedure if HCV RNA detectable

Can return to work is sustained virological response to antiviral therapy

106
Q

Child with CVID given regular immunoglobulin replacement. Which of the following tests cannot be explained by immunoglobulin replacement:

Detectable -
CMV IgG
EBV VCA IgG
HCV IgG
Anti-HBc
Toxoplasma IgG
A

HCV IgG

Pooled immunoglobulins contain large variety of immunoglobulins to various organisms, so patient will test positive to lots of organisms.

In UK, blood is screened for HIV, HTLV, HCV, so not expected to be present in immunoglobulin preparations.
CMV/ EBV/ toxoplasma/ HepB core antigen are not routinely screened for, and could appear as passive antigens

107
Q

What is definition of exposure prone procedure?

A

Exposure Prone Procedures (EPP) are invasive procedures where there is a risk that injury to the worker may result in the exposure of the patient’s open tissues to the blood of the worker (‘bleed-back’).

These include procedures where the worker’s gloved hands may be in contact with sharp instruments, needle tips or sharp tissues (e.g. spicules of bone or teeth) inside a patient’s open body cavity, wound or confined anatomical space where the hands or fingertips may not be completely visible at all times.

108
Q

Patient has following results:

HBsAg detected
HBeAG not detected
HBV DNA 10 000 IU/ml

Which of these procedures can they perform?

Arterial cutdown
Deep suturing cardiac arrest
Laparotomy
Repair perineal tear after delivery
Venepuncture
A

Venepuncture

Other procedures are exposure prone procedures. They carry risk of injury to worker, which may result in exposure of patient’s open tissues to the blood of the worker

Can perform EPP once viral load <1000 copies/ml

109
Q

47 year old with AML about to have stem cell transplant. Blood tests showe:

HBsAg - not detected
anti-HBc - detected
anti-HBs - <10mIU/ml
HBV DNA 340 IU/ml

What is appropriate management?

Accelerated HepB vaccination
No anti-viral treatment as HBsAg negative
Start adeofvir
Start entecavir or tenofovir
Start lamivudine
A

Blood tests suggest previous HBV exposure through infection. This means risk of possible reactivation.

Give 6 monts entecavir or tenofovir

Lamivudine would also be suitable, but resistance develops if used for longer periods such as 6 months

110
Q

HBsAg positive, with other serology negative.

What are possibilities for this?

A

False positive HBsAg - need to repeat on another platform, and perform neutralisation

False negative antibody test

Recent vaccination, but nor produced anti-HBs yet

Newly recently acquired HBV infection, and has not yet sero-converted

Patient with immunodeficiency or on chemotherapy - so produces inadequate antibody response. May have been infected at any time

111
Q

HBsAg positive
HBeAg positive
other serology negative

What is explanation for this?

A

Acute HBV infection

High viral replication, prior to immune response/ sero-conversion

112
Q

What is importance of genotyping a virus?

A

Check inherent resistance before treatment

Assess risk of cirrhosis/ HCC

Assess source of infection - certain genotypes associated with vertical or horizontal transmission

Epidemiological studies

Medical Microbiology and Virology (60 decks)

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