HCV Flashcards
What are the most common HCV genotypes in UK?
Genotypes UK
1a (32%)
1b (15%)
3a (37%)
What are the common 3 drug targets for DAAs?
NS3A/4A
NS5A
NS5B
NS3A/NS4A - Protease inhibitor - prevent cleavage polyprotein
NS5A - unknown - essential for replication
NS5B - RNA dependent RNA polymerase
What are common drug examples?
NS3A/ 4A
NS3A/NS4A - Protease inhibitor - prevent cleavage polyprotein
Grazeprovir
What are common drug examples?
NS5A
NS5A - unknown - essential for replication
Elbasavir
Velpatasvir
What are common drug examples?
NS5B
NS5B - RNA dependent RNA polymerase
Sofosbuvir
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
Child-Pugh Score
Bil
Alb
INR
Ascites
Encephalopathy
What is mortality rate of these Child Pugh classes?
A
B
C
1 year mortality
A - 13%
B - 65%
C - 69%
What are normal and abnormal fibroscan ranges?
<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)
What is Metavir score?
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
What is Ishak score?
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
What are transmission routes of HCV?
Blood - IVDU, transfusion
Sexual
Transplacental - possible but inefficient
How many patients with acute HCV infection develop acute hepatitis?
10% develop acute hepatitis
occurs about 6 weeks after HCV exposure
What percentage of patients infected with HCV develop chronic HCV infection?
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
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?
HIV/ HBV co-infection
smoking
obesity
alcohol use
male
older age at time of diagnosis
Patients with HCV and cirrhosis, are at risk of HCC
(if no cirrhosis, no risk of HCC)
What proportion of patients develop HCC?
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
Patient with needlestick injury
When and what blood tests should be taken?
At baseline - bloods for storage
6 weeks - HCV RNA
12 weeks - anti-HCV and HCV RNA
24 weeks - anti-HCV
HCV workup
What other testing is required?
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
What are indicators of advanced or decompensated cirrhosis?
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.
What are extra-hepatic manifestations of HCV?
Dermatology -
- Lichen planus
- Porphyria cutanea tarda
Liver -
- Diabetes mellitus
Lymphotropism -
- Cryoglobulinaemia
- Vasculitis
- Non-Hodgkin’s Lymphoma - B cell
Renal -
- Membranoproliferative glomerulonephritis
When is HCV infection classified as chronic?
Detectable HCV RNA >6 months
When picking an HCV RNA PCR assay, what is an acceptable lower limit of detection?
<15 IU/ml
At what prevalence would it be recommended to start routine population/ cohort screening?
e.g antenatal screening
2% - 5% would indicate intermediate to high seroprevalence
What percentage of patients with SVR12 relapse?
(not reinfected)
<1%
99% of patients with SVR12 will have permanently cleared the virus
HCV positive patient, normal ALT
Why do they need non-invasive assessment of liver fibrosis?
Since significant fibrosis may be present in patients with repeatedly normal ALT, evaluation of disease severity should be performed regardless of ALT levels.
HCV genotyping is required before starting treatment
Why is resistance testing not performed initially?
Difficult to perform - genotypic only
Even is they has Resistance Associated Substitutions (RASs), most first line DAAs are still effective, in treatment naïve population
What are the rules regarding organ donation in patients who are HCV RNA positive?
HCV RNA positive can be transplanted into HCV RNA negative patients
Recipient must start HCV DAA rapidly following transplantation
PWID who have cleared HCV infection.
How often should they be offered HCV RNA screening?
If ongoing risk factors for infection, screen every 6-12 months
What is the nucelotide difference percentage between these terminologies?
Genotype
Subtype
Quasispecies
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
