HCV Treatment guidelines Flashcards
After stating HCV treatment, what is the follow up procedure?
Weeks 2-4:
Contact (usually by telephone) to assess for compliance and complications
Weeks 4-end of treatment:
Contact depending on case complexity and support requirements
Week 12 - End of treatment:
HCV RNA check for SVR
LFT
Fibroscan - if >7kPa at initial assessment
If Fibroscan is >7kPa at initial assessment, will need follow up for fibrosis/ cirrhosis/ HCC in future, even once cleared HCV
HCV patient completed 12 weeks treatment
When can they be discharged from clinic?
Discharge
Following SVR12 assessment, patients should be discharged if the following criteria are met:
- FibroScan score < 7kPa
- Normal LFT, plt and PT
Advice should be given regarding blood borne virus prevention, vaccination recommendations and liver disease risk factor avoidance.
How are patients prioritised for HCV treatment?
- Liver function - patients with liver failure will receive top priority.
- Liver disease stage - more severe will be prioritised
- Medical co-morbidities. Examples include medical complications of hepatitis C, liver cancer, HIV and conditions that require immunosuppression such as liver transplantation.
- Other hepatitis C associated complications
- Infection risk to others
- Patient being within a limited “treatment window”
- Iatrogenic infection
- Time on waiting list
Treatment of genotype 1 & 4
Non-cirrhotic
First line
Grazeprovir NS3A/NS4A
Elbasavir NS5A
12 weeks
Treatment of genotype 1 & 4
Cirrhotic - compensated
First line
Grazeprovir NS3A/NS4A
Elbasavir NS5A
12 weeks
Treatment of genotype 2/ 3/ 5/ 6
Non-cirrhotic
First line
Velpatasvir NS5A
Sofosbuvir NS5B
12 weeks
Treatment of genotype 2/ 3/ 5/ 6
Cirrhotic - compensated
First line
Velpatasvir NS5A
Sofosbuvir NS5B
12 weeks
+/- ribavirin for genotype 3
Treatment of genotype 1 - 6
Cirrhotic - decompensated
First line
Genotype 1 -
- Ledipasavir
- Sofosbuvir
- Ribavirin
Genotype 2-6 -
- Velpatasavir
- Sofosbuvir
- Ribavirin
12 weeks
HCV DAA treatment duration normally 12 weeks
In what circumstances would you extend to 16 weeks?
Consider increasing to 16 weeks, and adding ribavirin -
- genotype 1a
- high viraemia - >800 000 copies
- NS5A RAVs (resistance associated variants)
Patient is re-infected with HCV, following successful treatment of previous infection
What are first line drugs for re-infection?
Given it is a new infection, treat with first line therapy depending on genotype
HCV DAA treatment failure
Without decompensated cirrhosis
What is rescue treatment option?
Voxilaprevir NS3A/ NS4A
Velpatasvir NS5A
Sofosbuvir NS5B
12 weeks
Make sure to re-genotype virus, and check for resistance mutations
HCV DAA treatment failure
With decompensated cirrhosis
What is rescue treatment option?
Sofosbuvir
Velpatasvir
Ribavirin
24 weeks
HCV/ HBV co-infection
How to decide which to treat first?
Viral loads to assess which disease is dominant - this should be treated first
Once the dominant virus has controlled, close observation is required as it may have been suppressing the other virus, which could then require treatment.
HCV/ HIV co-infection
HIV is significant risk factor for HCV disease progression, so would want to treat early. However, many drug interactions.
What is recommended treatment goals in these patient groups:
- CD4 <350
- CD4 350 - 500
- CD4 >500
1) In the presence of co-infection, if CD4 count is < 350 x 106 cells/L then HIV therapy is recommended. If treatment for HCV is being instigated then HIV therapy should be established first.
2) If CD4 count is 350-500 x 106 cells/L and HCV treatment is required, HIV therapy should be instigated first.
3) If CD4 count is > 500 x 106 cells/L then HCV treatment can be instigated before HIV therapy is required.
What are common examples of
NS3A/ NS4A DAA
NS3A/ NS4A DAA
Glecaprevir*
Grazeprovir
Voxilaprevir
*less commonly used
What are common examples of
NS5A DAA
NS5A DAA
Elbasavir
Ledipasvir
Pibrentasvir*
Velpatasvir
*less commonly used
What are common examples of
NS5B DAA
NS5B DAA
Sofosbuvir
What is the drug name for combination therapy
Ledipasvir-sofosbuvir
Elbasvir-grazoprevir
Ledipasvir-sofosbuvir - Harvoni
Elbasvir-grazoprevir - Zepatier
What is the drug name for combination therapy
Sofosbuvir-velpatasvir
Sofosbuvir-velpatasvir-voxilaprevir
Sofosbuvir-velpatasvir - Epclusa
Sofosbuvir-velpatasvir-voxilaprevir - Vosevi
What is the drug name for combination therapy
Glecaprevir-pibrentasvir
Glecaprevir-pibrentasvir - Mavyret
What are common side effects of DAA drugs?
Fatigue 50%
GI symptoms 40% (diarrhoea/ nausea)
Headache 15%
Anaemia 15% (ribavirin main culprit)
Photosensitivity 5%
Dyspnoea 2%
Approximately 30% patients on therapy develop side effects
Patients on NS3/4A inhibitors, ribavirin, or interferon require FBC monitoring
NS5A/ NS5B inhibitors do not require any specific monitoring
Interferon and ribavirin are older treatment options
What are common side effects?
Fatigue
GI symptoms
Anaemia - haemolytic
Thrombocytopenia
Neutropenia
Dyspnoea
Flu-like symptoms
Rashes
Interferon is an old drug used for HCV treatment
What is the mode of action?
Targets hepatocytes and immune cells - upregulates host immune response
Ribavirin is an older drug, occasionally still used as HCV treatment
What is its mode of action?
Nucleoside guanosine analogue
Stops viral RNA synthesis
What are contraindications to DAAs?
Cytochrome P450 inducing agents - reduce levels of DAAs
- carbamazepine
- phenytoin
- rifampicin
- St John’s wart
Anti-arrhythmic drugs (sofosbuvir)
- amiodarone
Protease inhibitors (NS3A/4A) contraindicated in Child Pugh B/C cirrhosis
Sofosbuvir - if eGFR <30
Patient with decompensated HCV cirrhosis, requiring transplant.
What treatment should be initiated?
If transplant required, then perform transplant first, and treat HCV after
Why is sofosbuvir contraindicated in renal disease?
<30 eGFR contraindicated
sofosbuvir is 80% renally excreted
metabolite can accumulate in renal failure
Why is sofosbuvir contraindicated in cardiac patients?
Interacts with - amiodarone - risk of life-threatening arrhythmia
May need to wait 3 months for amiodarone to wash out system, before starting sofosbuvir.
Can start sooner if have pacemaker in situ
HIV and HCV drug interactions
Which HIV drugs are contra-indicated with HCV DAAs?
NRTI
NNRTI
PI
INT
NRTI -
- tenofovir - potential interaction
NNRTI
- efavirenz - severe
- nevirapine - severe
PI
- Atazanavir/ ritonavir - severe
- Darunavir/ ritonavir - severe
- Lopinavir/ ritonavir - severe
INT
- none
Sofosbuvir is good as does not interact with any HIV medication
What are common drug contra-indications between HCV DAAs and lipid lower drugs
Significant interaction -
- atorvastatin
- simvastatin
No interaction -
- ezetimibe
Sofosbuvir is good as does not interact with lipid lowering medication
Which DAAs do antacids interact with?
Antacids
PPI
H2 antagonist
Increased gastric pH decreases absorption of -
- NS5A - Ledipasavir/ Velpatasvir
- NS5B - Sofosbuvir
Can still take antacids, but may need to move doses around.
e.g take 4 hours before PPI dose
Which HCV DAAs are contra-indicated in patients on anti-coagulants/ anti-platelets?
Sofosbuvir is ok with all, except warfarin - potential interaction
Rest of DAAs should be avoided if possible
What is advice for women on oral contraceptive pill, starting HCV DAAs?
- Combined oral contraceptive pill contra-indicated - associated with raised ALT
- Progesterone only pill is allowed
- Recommend other forms of contraception
What is advice for women who are breast feeding, on DAAs?
Avoid breast feeding if possible - safety has not yet been established
What are risks of ribavirin in pregnancy?
Teratogenic
Women must be on appropriate contraception
Combined OCP is contra-indicated
Why are Protease inhibitors (NS3A/4A) contraindicated in Child Pugh B/C cirrhosis?
Increase levels of protease inhibitors in cirrhosis
Can lead to liver decompensation
Patient with HCV infection, about to start treatment
Patient also HBsAg positive
How does this affect HCV treatment?
If HBsAg positive, and meet criteria for HBV treatment - should be started on both treatment for HCV and HBV
If HBsAg positive, but HBV is not current problem, offer 12 weeks nucleoside/ nucleotide analogue therapy prophylaxis until HCV therapy complete
Treating HCV infection can allow HBV to become dominant virus, and lead to worsening hepatitis, so prophylaxis is recommended
Patient with HCV infection, about to start treatment
Patient is HBsAg neg, but antiHBc pos
How does this affect HCV treatment?
Monitor ALT levels
If they do not improve or worsen on HCV therapy, then check HBsAg and HBV DNA again.
If detected, then initiate nucleoside/ nucleotide analogue therapy
Patients with severe renal disease eGFR <30
What are treatment options?
glecaprevir + pibrentasavir for 12 weeks
Avoid sofosbuvir
Other drugs may be used if there is resistance, but close monitoring is required
Patient shown to have acute HCV infection
When should treatment be offered?
Better outcomes if treatment offered early, before chronicity develops (90% develop chronic infection)
ledipasavir
sofosbuvir
8 weeks
recommended regimen
Nurse receives needlestick injury from man who is known HCV RNA positive yesterday
Should PEP be offered?
DAAs are not indicated unless HCV RNA is detected in recipient
Not to be used as PEP
Patient develops severe anaemia on ribavirin
When should treatment be stopped?
Anaemia is dose dependent
Reduce dose by 200mg increments until Hb stabilises
Rising ALT whilst on DAAs
When should treatment be stopped?
Treatment should be stopped in case of severe adverse events, or in case of ALT flare >10x upper limit normal
