HCV Flashcards

1
Q

What are the most common HCV genotypes in UK?

A

Genotypes UK
1a (32%)
1b (15%)
3a (37%)

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2
Q

What are the common 3 drug targets for DAAs?

NS3A/4A
NS5A
NS5B

A

NS3A/NS4A - Protease inhibitor - prevent cleavage polyprotein

NS5A - unknown - essential for replication

NS5B - RNA dependent RNA polymerase

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3
Q

What are common drug examples?

NS3A/ 4A

A

NS3A/NS4A - Protease inhibitor - prevent cleavage polyprotein

Grazeprovir

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4
Q

What are common drug examples?

NS5A

A

NS5A - unknown - essential for replication

Elbasavir
Velpatasvir

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5
Q

What are common drug examples?

NS5B

A

NS5B - RNA dependent RNA polymerase

Sofosbuvir

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6
Q

What are components of Child-Pugh score?

Used to predict mortality risk in patients with cirrhosis.
Stratify who needs treatment, and who may need transplant

A

Child-Pugh Score

Bil
Alb
INR
Ascites
Encephalopathy

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7
Q

What is mortality rate of these Child Pugh classes?

A
B
C

A

1 year mortality

A - 13%
B - 65%
C - 69%

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8
Q

What are normal and abnormal fibroscan ranges?

A

<7 kPa - normal (Metavir 0/1)

7 - 9.5 kPa - mild (Metavir 2)

9.5 - 12.5 kPa - moderate (Metavir 3)

> 12.5 kPa - severe (Metavir 4)

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9
Q

What is Metavir score?

A

histological staging

used to evaluate the severity of fibrosis seen on a liver biopsy
from a person who has hepatitis C

F0 - no fibrosis
F1 - fibrosis occasional
F2 - fibrosis with occasional bridging
F3 - fibrosis, marked bridging between zones
F4 - cirrhosis

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10
Q

What is Ishak score?

A

histological staging

  • 0 no fibrosis
  • 1 fibrous expansion of some portal areas, with or without short fibrous septa
  • 2/3/4 fibrous expansion in portal areas
  • 5 marked bridging between fibrous areas with occasional nodules (incomplete cirrhosis)
  • 6 cirrhosis, probable or definite
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11
Q

What are transmission routes of HCV?

A

Blood - IVDU, transfusion
Sexual
Transplacental - possible but inefficient

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12
Q

How many patients with acute HCV infection develop acute hepatitis?

A

10% develop acute hepatitis
occurs about 6 weeks after HCV exposure

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13
Q

What percentage of patients infected with HCV develop chronic HCV infection?

A

Chronic defined as HCV RNA detectable >6 months after infection

20% clear spontaneously
80% chronic infection

Chronic infection tends to be progressive, than relapsing remitting

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14
Q

80% of those infected with HCV develop chronic infection.

20% of those with chronic infection develop cirrhosis within 10-30 years

What are risk factors for progression to cirrhosis?

A

HIV/ HBV co-infection
smoking
obesity
alcohol use
male
older age at time of diagnosis

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15
Q

Patients with HCV and cirrhosis, are at risk of HCC
(if no cirrhosis, no risk of HCC)

What proportion of patients develop HCC?

A

The annual risk of HCC in HCV with cirrhosis is 3 to 5%

Even after HCV infection is cleared, patients with cirrhosis will still require follow up 6 monthly USS for HCC

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16
Q

Patient with needlestick injury

When and what blood tests should be taken?

A

At baseline - bloods for storage

6 weeks - HCV RNA

12 weeks - anti-HCV and HCV RNA

24 weeks - anti-HCV

17
Q

HCV workup

What other testing is required?

A

HCV RNA
HCV genotyping

HAV immunity
HBV immunity

USS liver - check for cirrhosis

Other liver screen - liver autoantibodies, immunoglobulins, Alpha-1-antitrypsin, caeruloplasmin, ferritin, HbA1c

FBC, UE, LFT, Coag

18
Q

What are indicators of advanced or decompensated cirrhosis?

A

Definitions of advanced or decompensated cirrhosis -

  • Evidence of present or previous decompensated cirrhosis with an episode of ascites, variceal bleeding, or encephalopathy
  • Child Pugh Score ≥ or = 7
  • The patient is at significant risk of death or irreversible damage. For example, patient is currently listed for liver transplantation
  • The patient has biochemical or haematological indicators of advanced cirrhosis and/or significant portal hypertension eg albumin < 35, platelets < 50.
19
Q

What are extra-hepatic manifestations of HCV?

A

Dermatology -
- Lichen planus
- Porphyria cutanea tarda

Liver -
- Diabetes mellitus

Lymphotropism -
- Cryoglobulinaemia
- Vasculitis
- Non-Hodgkin’s Lymphoma - B cell

Renal -
- Membranoproliferative glomerulonephritis

20
Q

When is HCV infection classified as chronic?

A

Detectable HCV RNA >6 months

21
Q

When picking an HCV RNA PCR assay, what is an acceptable lower limit of detection?

A

<15 IU/ml

22
Q

At what prevalence would it be recommended to start routine population/ cohort screening?
e.g antenatal screening

A

2% - 5% would indicate intermediate to high seroprevalence

23
Q

What percentage of patients with SVR12 relapse?
(not reinfected)

A

<1%

99% of patients with SVR12 will have permanently cleared the virus

24
Q

HCV positive patient, normal ALT

Why do they need non-invasive assessment of liver fibrosis?

A

Since significant fibrosis may be present in patients with repeatedly normal ALT, evaluation of disease severity should be performed regardless of ALT levels.

25
Q

HCV genotyping is required before starting treatment

Why is resistance testing not performed initially?

A

Difficult to perform - genotypic only

Even is they has Resistance Associated Substitutions (RASs), most first line DAAs are still effective, in treatment naïve population

26
Q

What are the rules regarding organ donation in patients who are HCV RNA positive?

A

HCV RNA positive can be transplanted into HCV RNA negative patients

Recipient must start HCV DAA rapidly following transplantation

27
Q

PWID who have cleared HCV infection.

How often should they be offered HCV RNA screening?

A

If ongoing risk factors for infection, screen every 6-12 months

28
Q

What is the nucelotide difference percentage between these terminologies?

Genotype
Subtype
Quasispecies

A

Genotype - genetic heterogeneity among different HCV isolates 65%-75% similar

Subtype - closely related isolates within each of the major genotypes >75% similar

Quasispecies - complex of genetic variants within individual isolates >90% similar