All Wales Hepatitis C treatment guidelines

All Wales Hepatitis C treatment guidelines

This guidance has been produced by the All Wales Hepatitis C group. Updated January 2024, unless otherwise stated.

This content is hosted by WMAS. While externally developed by the All Wales Hepatitis C group, we believe it has undergone appropriate governance and review processes. WMAS publish this content to support safe and effective patient care.

On this page
1. Basic principles
2. Resistance testing
3. Drug-drug interactions
4. Virtual panel
5. Video Observed Therapy (VOT)
6. Treatment recommendations
7. Prison guidelines for hepatitis C
8. Community guidelines for hepatitis C

Basic principles

  • Adhere to principles of Prudent Healthcare
  • Meet the World Health Organisation elimination targets
  • Find patients, link them to care and deliver treatment successfully
  • #gettestedgetcured 
  • Individualised treatments based on most appropriate treatment for each patient (Healthcare professionals in partnership with patients free to choose the most appropriate agent)
  • Reduce barriers to treatment including simplification of treatment pathways
  • Use of pan-genotypic agents (Maviret or Epclusa) once the PCR result is known and prior to the genotype being made available where appropriate to simplify treatment regime and improve access to care
  • Drugs listed in price order
  • The cheapest agent should be used whenever possible.  However, nothing is more costly than treatment failure and as such, treatment should be tailored to the individual.
  • Treatment choice will be influenced by cost, pill burden, drug-drug interactions, treatment duration, availability of genotype, renal failure, adherence and other patient characteristics / circumstances (list not exhaustive).
  • Panel approval required for all DAA treatment failure patients so that the most appropriate treatment can be given
  • Panel approval required for use of expensive medications –  e.g. Vosevi, Sofosbuvir + Maviret, Zepatier to ensure that there is not a cheaper suitable alternative.
  • The following have been removed from the guidelines in order to simplify the guidelines but are still available and can be prescribed if necessary (panel approval recommended): Sofosbuvir/Pegylated interferon/ribavirin, Zepatier, Sofosbuvir + ribavirin
  • Developing services that will enable treatment in the community is essential for delivery against WHO elimination targets

Resistance testing

The type of resistance testing performed depends on patient and viral characteristics as well as the regimen being considered. NS5A resistance testing should be tested for in the following circumstances:

  • Genotype 3 cirrhotics
  • Prior to Zepatier (apart from certain circumstances)
  • Decompensated cirrhosis
  • Genotypes 4, 5 and 6
  • Prior DAA treatment failure

Drug-drug interactions

All treatment should be administered in line with SPC recommendations and drug-drug interactions checked on the Liverpool website https://www.hep-druginteractions.org/checker

Virtual panel

A virtual panel is available to provide advice. Please refer via the following link:

Cases that are not straightforward can be sent to the panel for review.  The panel will consist of the 6 BBV leads, Matthijs Backx, Rhys Oakley with one external representative from England (David Mutimer) who will be co-opted for difficult cases.  A record of all decisions will be kept. 

The following cases should be sent for review. 

  1. Previous Direct Acting Antiviral failure patients
  2. Non standard regime being considered
  3. Patients requiring expensive regimes (e.g. Vosevi, Sofosbuvir + Maviret, Zepatier)
  4. Decompensated cirrhotic patients in whom 24 week treatment is considered desirable

Any patient can be referred to the virtual panel for an opinion.  Reasons for referral (not exhaustive) could include requests for opinions on:

  1. A patient’s suitability for treatment (e.g. will treatment likely result in an  increased life expectancy or significant improvement in quality of life)
  2. Choice of regime
  3. Duration of regime
  4. Use of ribavirin
  5. Use outside SPC recommendation
  6. Use of regime including protease inhibitor for patients with Child Pugh B & C

Video Observed Therapy (VOT)

VOT has been used in tuberculosis with high reported levels of patient acceptability and reduced costs compared to Directly Observed Therapy (DOT). VOT is an option for hepatitis C patients who require adherence support.

VOT involves patients being provided with a smartphone and a sim card with unlimited minutes and sufficient data to support sending videos. The smart phone and sim card will be sent to a location of your choice. The videos willl be observed by a central team and there will be no requirement for observing the video by the treating team. The central team will contact the treating team if videos have not been uploaded on 3 consecutive days. Videos are deleted immediately after viewing.

Patients will be required to sign agreement forms which will be provided by the central team.

If you think VOT is an option for your patient please contact Brendan Healy / Rhys Oakley / Michelle Robinson

Treatment recommendations

Pan-Genotype

Can be used in treatment naïve PCR positive patients prior to genotype being available.

Non-cirrhotic
  1. Maviret (glecaprevir / pibrentasvir)
  2. Epclusa (sofosbuvir / velpatasvir) 1

8 weeks

12 weeks

Compensated cirrhosis (Child Pugh A only)

Consider waiting for genotype and baseline resistance testing prior to initiation of treatment in G3.

  1. Maviret (glecaprevir / pibrentasvir)
  2. Epclusa (sofosbuvir / velpatasvir) +/- ribavirin 2
    (SVR without ribavirin 93%)

8 weeks

12 weeks

Decompensated cirrhosis (Child Pugh B or C)

Consider waiting for genotype +/- baseline resistance testing prior to initiation of treatment.

  1. Epclusa (sofosbuvir / velpatasvir) + ribavirin

12 weeks

For dosing see product literature.

1 Note: If Epclusa is used as a pan-genotypic and at a later date the patient is shown to have G1 and meet the criteria for 8 weeks Harvoni, then Gilead will provide a rebate so that the cost is the same as 8 weeks Harvoni – inform your local pharmacy team who will request the rebate.

2 Note: At present there is no evidence that ribavirin improves SVR rate in these patients. However, the SVR rate for these groups is less than 95% when treated with Epclusa alone. Ribavirin is generally well tolerated. As such, consideration should be given to adding ribavirin in the first instance. It would be reasonable (due to the lack of evidence of benefit) to have a relatively low threshold for stopping ribavirin in these patients. The following negative predictive factors should be taken into account when assessing use of ribavirin: NS5A RAVs, presence of cirrhosis, baseline HCV RNA ≥800,000 IU/mL, Platelets <100 x 103/µL, Albumin <35, FibroScan > 15.

Genotype 1a

Order of preference based on cost.

Non-cirrhotic
  1. Harvoni (sofosbuvir / ledipasvir) 3
  2. Maviret (glecaprevir / pibrentasvir)
  3. Epclusa (sofosbuvir / velpatasvir)
  4. Harvoni (sofosbuvir / ledipasvir) 5
  5. Harvoni (sofosbuvir / ledipasvir) 5 + ribavirin

8 weeks (FS < 12.5) 4

8 weeks

12 weeks

12 weeks

12 weeks

Compensated cirrhosis (Child Pugh A only)
  1. Maviret (glecaprevir / pibrentasvir)
  2. Epclusa (sofosbuvir / velpatasvir)
  3. Harvoni (sofosbuvir / ledipasvir) 5
  4. Harvoni (sofosbuvir / ledipasvir) 5 + ribavirin

8 weeks

12 weeks

12 weeks

12 weeks

Decompensated cirrhosis (Child Pugh B or C)

Consider baseline resistance testing.

  1. Epclusa (sofosbuvir / velpatasvir) + ribavirin 6
  2. Harvoni (sofosbuvir / ledipasvir) + ribavirin 6

12 weeks

12 weeks

For dosing see product literature.

3 Cut off FibroScan score of 12.5 used in the registrational studies.

4 Optimal duration in this group has not been categorically determined. 8 weeks treatment has a high success rate (93%) and should be used whenever possible. Treatment guidelines recommend 8 week duration in treatment naïve patients with viral loads < 6 million IU/mL. “Real world” data from Germany suggests that 8 week treatment duration is suitable in other categories of patients as well (e.g. treatment experienced – small numbers and not recommended by NHS England) and that the stage of disease may be a more reliable predictor of success. AASLD guidance recommends NOT shortening treatment in HIV patients. Cut off FibroScan score of 12.5 used in the registrational studies.

EASL 2016 guidance states “Treatment can be shortened to 8 weeks in treatment-naïve patients without cirrhosis if their baseline HCV RNA level is below 6 million (6.8 Log) IU/mL. This should be done with caution in patients with F3 disease.”

As there are suitable alternatives (including some with 8 week duration) and cost is no longer such a significant issue we can afford to be more conservative with the use of shortened 8 week therapy of Harvoni (sofosbuvir / ledipasvir) – i.e. use in treatment naïve patients with viral loads < 6 million IU/ml and F0-F2 disease.

5 If there is no suitable alternative ribavirin should be added to those who are G1a treatment experienced. SVR rates are around 90% if Harvoni is used for 12 weeks without ribavirin.

6 If ribavirin is not tolerated or unable to be used, then perform resistance test and refer to virtual panel.

Genotype 1b

Order of preference based on cost.

Non-cirrhotic
  1. Harvoni (sofosbuvir / ledipasvir) 7
  2. Maviret (glecaprevir / pibrentasvir)
  3. Epclusa (sofosbuvir / velpatasvir)
  4. Harvoni (sofosbuvir / ledipasvir)

8 weeks (FS < 12.5) 8

8 weeks

12 weeks

12 weeks

Compensated cirrhosis (Child Pugh A only)
  1. Maviret (glecaprevir / pibrentasvir)
  2. Epclusa (sofosbuvir / velpatasvir)
  3. Harvoni (sofosbuvir / ledipasvir)

8 weeks

12 weeks

12 weeks

Decompensated cirrhosis (Child Pugh B or C)

Consider baseline resistance testing

  1. Epclusa (sofosbuvir / velpatasvir) + ribavirin 9
  2. Harvoni (sofosbuvir / ledipasvir) + ribavirin 9

12 weeks

12 weeks

For dosing see product literature.

7 Cut off FibroScan score of 12.5 used in the registrational studies.

8 Optimal duration in this group has not been categorically determined. 8 weeks treatment has a high success rate (93%) and should be used whenever possible. Treatment guidelines recommend 8 week duration in treatment naïve patients with viral loads < 6 million IU/mL. “Real world” data from Germany suggests that 8 week treatment duration is suitable in other categories of patients as well (e.g. treatment experienced – small numbers and not recommended by NHS England) and that the stage of disease may be a more reliable predictor of success. AASLD guidance recommends NOT shortening treatment in HIV patients. Cut off FibroScan score of 12.5 used in the registrational studies.

EASL 2016 guidance states “Treatment can be shortened to 8 weeks in treatment-naïve patients without cirrhosis if their baseline HCV RNA level is below 6 million (6.8 Log) IU/mL. This should be done with caution in patients with F3 disease.”

As there are suitable alternatives (including some with 8 week duration) and cost is no longer such a significant issue we can afford to be more conservative with the use of shortened 8 week therapy of Harvoni (sofosbuvir / ledipasvir) – i.e. use in treatment naïve patients with viral loads < 6 million IU/ml and F0-F2 disease.

9 If ribavirin is not tolerated or unable to be used, then perform resistance test and refer to virtual panel.

Genotype 2

Non-cirrhotic
  1. Maviret (glecaprevir / pibrentasvir)
  2. Epclusa (sofosbuvir / velpatasvir)

8 weeks

12 weeks

Compensated cirrhosis (Child Pugh A only)
  1. Maviret (glecaprevir / pibrentasvir)
  2. Epclusa (sofosbuvir / velpatasvir)

8 weeks

12 weeks

Decompensated cirrhosis (Child Pugh B or C)
  1. Epclusa (sofosbuvir / velpatasvir) + ribavirin

12 weeks 10

For dosing see product literature.

10 There is limited data on the treatment of genotype 2 patients with decompensated cirrhosis. SmPC recommends use with ribavirin.  The risks and benefits of ribavirin need to be carefully considered in this group. If ribavirin is not tolerated or unable to be used, then perform resistance test and refer to virtual panel.

Genotype 3

Treatment experienced (TE) defined as peg IFN + ribavirin + /- sofosbuvir or sofosbuvir + ribavirin. For combination DAA treatment failures see later section.

Non-cirrhotic

  1. Maviret (glecaprevir / pibrentasvir)
  2. Epclusa (sofosbuvir / velpatasvir)
  3. Vosevi (sofosbuvir / velpatasvir / voxilaprevir) 11

Treatment naïve (TN)

8 weeks

12 weeks

n/a

Treatment experienced (TE)

16 weeks

12 weeks

12 weeks 11

Compensated cirrhosis (Child Pugh A only)

Consider baseline resistance testing (NS5A) prior to initiation of treatment in patients with significant markers of poor response. 12

If Y93H present, then ribavirin will need to be added to Epclusa or Maviret used instead. If no Y93H present, then Epclusa can be used without ribavirin.

  1. Maviret (glecaprevir / pibrentasvir)
  2. Epclusa (sofosbuvir / velpatasvir) +/- ribavirin 12
    (SVR without ribavirin 93%)
  3. Vosevi (sofosbuvir / velpatasvir / voxilaprevir) 11

Treatment naïve (TN)

8 weeks

12 weeks

12 weeks 11

Treatment experienced (TE)

16 weeks

12 weeks

12 weeks 11

Decompensated cirrhosis (Child Pugh B or C)

Baseline resistance testing recommended.

  1. Epclusa (sofosbuvir / velpatasvir) +/- ribavirin 13

Treatment naïve (TN)

12 weeks

Treatment experienced (TE)

12 weeks

For dosing see product literature.

11 Panel approval required.

12 Note: At present there is no evidence that ribavirin improves SVR rate in these patients. However, the SVR rate for these groups is less than 95% when treated with Epclusa alone. Ribavirin is generally well tolerated. As such, consideration should be given to adding ribavirin in the first instance. It would be reasonable (due to the lack of evidence of benefit) to have a relatively low threshold for stopping ribavirin in these patients. The following negative predictive factors should be taken into account when assessing use of ribavirin: NS5A RAVs, presence of cirrhosis, baseline HCV RNA ≥800,000 IU/mL, Platelets <100 x 103/µL, Albumin <35, FibroScan > 15.

13 If ribavirin is not tolerated or unable to be used, then perform resistance test and refer to virtual panel.

Genotype 4

Baseline resistance testing recommended.

Order of preference based on cost.

Non-cirrhotic
  1. Maviret (glecaprevir / pibrentasvir)
  2. Epclusa (sofosbuvir / velpatasvir)
  3. Harvoni (sofosbuvir / ledipasvir) 14

8 weeks

12 weeks

12 weeks

Compensated cirrhosis (Child Pugh A only)
  1. Maviret (glecaprevir / pibrentasvir)
  2. Epclusa (sofosbuvir / velpatasvir)
  3. Harvoni (sofosbuvir / ledipasvir) 14,15

8 weeks

12 weeks

12 weeks

Decompensated cirrhosis (Child Pugh B or C)
  1. Epclusa (sofosbuvir / velpatasvir) + ribavirin 16
  2. Harvoni (sofosbuvir / ledipasvir) + ribavirin 15,16

12 weeks

12 weeks

For dosing see product literature.

14 Resistance testing strongly encouraged prior to use and only to be used if no other suitable alternative.

15 Note: Harvoni (sofosbuvir / ledipasvir) +/- ribavirin not recommended by BVHG due to paucity of data.

16 If ribavirin is not tolerated or unable to be used, then perform resistance test and refer to virtual panel.

Genotype 5, 6

Note: Limited data for these genotypes. Resistance testing recommended prior to treatment.

Non-cirrhotic
  1. Maviret (glecaprevir / pibrentasvir)
  2. Epclusa (sofosbuvir / velpatasvir)

8 weeks

12 weeks

Compensated cirrhosis (Child Pugh A only)
  1. Maviret (glecaprevir / pibrentasvir)
  2. Epclusa (sofosbuvir / velpatasvir)

8 weeks

12 weeks

Decompensated cirrhosis (Child Pugh B or C)
  1. Epclusa (sofosbuvir / velpatasvir) + ribavirin 17

12 weeks 18

For dosing see product literature.

17 If ribavirin is not tolerated or unable to be used, then perform resistance test and refer to virtual panel.

18 There is limited data on the treatment of genotype 5 and 6 patients with decompensated cirrhosis. SmPC recommends use with ribavirin. The risks and benefits of ribavirin need to be carefully considered in this group. If ribavirin is not tolerated or unable to be used, then perform resistance test and refer to virtual panel.

DAA Treatment Experienced

Repeat genotype (to exclude re-infection rather than relapse).

Resistance test required prior to retreating.

Panel approval required for DAA experienced patients.

To refer to panel, please complete the following MS form:
https://forms.office.com/Pages/ResponsePage.aspx?id=uChWuyjjgkCoVkM8ntyPrjNDSJPy1vNFvXFtKluB_E9UMjRLQjVFNDdXNkVHQkMzWEEyS05DRU1ZUy4u

Prison guidelines for hepatitis C

From: All Wales Rapid Care Pathway for the treatment of hepatitis C, version 1. March 2022

 Only the following information is required before treatment initiation:

  • Confirmation of hepatitis C viraemia (cepheid, microtubule or venepuncture)
  • Drug-drug interaction (DDI) check using the Liverpool University website

Exclusions:

  • Relapsed patients (may have resistant virus and must be dealt with by the BBV team in collaboration with the National MDT)
  • Hepatitis B surface antigen positive patients (may need additional treatment and will need to be assessed and managed by the local BBV team) 
  • Newly diagnosed HIV (may need additional treatment and will need to be assessed and managed by local BBV team)

Treatment options

Pan-genotypic agents are recommended to speed up and improve access to therapy. Both Maviret (glecaprevir / pibrentasvir) and Epclusa (sofosbuvir / velpatasvir) are extremely well tolerated with very few side effects. Epclusa should be favoured if there is any concern about the presence of cirrhosis. Maviret may be preferred if a shorter duration of therapy is desired.

Monitoring prior to therapy

Prior to treatment, it is preferable (but not required to initiate therapy) to assess liver disease severity with an APRI score or FibroScan and to check the following bloods:

  • FBC (venepuncture or microtubule) (needs local agreement)
  • U&E, LFT (venepuncture or microtubule) (needs local agreement)
  • INR (venepuncture)
  • Hep C PCR (cepheid, microtubule or venepuncture)
  • Hep C genotype (venepuncture)
  • Hep B (venepuncture or DBST)
  • HIV serology (venepuncture or DBST)
  • Hep A (venepuncture)

Any hep B (sAg positive) and/or HIV positive cases should be referred to the local BBV team.

Those susceptible to hepatitis B and hepatitis A should be vaccinated whilst in prison. 

Pathways

Below are two suggested treatment pathways for individuals in the prison setting in Wales depending on the testing methods available. They are intended for treatment naïve or reinfected patients (individuals with a documented SVR and subsequent new infection).

For these pathways to succeed it is imperative that treatments are readily accessible. Prison pharmacies should have a stock of the pan-genotypic agents Maviret (glecaprevir / pibrentasvir) and Epclusa (sofosbuvir / velpatasvir) available to prevent delays in initiation of treatment. Both agents are extremely well tolerated with very few side effects. Epclusa should be favoured if there is any concern about pill burden or the presence of cirrhosis. Maviret may be preferred if a shorter duration of therapy is desired.

An assessment should take place using the local risk assessment tool to determine whether an individual should receive treatment in possession or not. Wherever possible treatment in possession is preferred to avoid the risk of missed doses through inability to access treatment. Note: treatment interruption in HCV treatment can lead to the development of resistance and complicate future treatment options – this must be taken into account during any risk assessment of whether or not to administer treatment in possession.

Patients should be strongly encouraged to take ownership of their health and ensure they take their medication with them if they are transferred to another prison or released early (prison nursing and pharmacy staff should alert the local BBV team to these situations). A one-week buffer of medication should be given at the outset of treatment to mitigate the risk of being released or transferred without medication where appropriate.

For individuals on an opioid substitution therapy programme (e.g. methadone or buprenorphine) who are required to collect their medication, and have it observed daily then their hepatitis C treatment should be administered at the same time (i.e. not in possession).

Remote consultation (e.g. Attend Anywhere) is encouraged to reduce barriers to and speed up access to treatment.

In addition, remote access to SystmOne (or alternative electronic patient record) is also encouraged to aid remote oversight of patients and improve governance.

On treatment monitoring is generally not needed but may be required in certain circumstances, e.g. if co-infected with Hep B (to receive treatment or be monitored for reactivation), if there is a risk of a drug-drug interaction causing toxicity, or if baseline bloods show significantly abnormal renal and/or liver function.

Significant side effects and poor compliance (frequently missed medication or long treatment interruption) should be discussed with the local BBV team or pharmacist (whoever is overseeing treatment).

Completion of a Hepatitis C e-form via Welsh Clinical Portal is required to inform the national elimination programme and aid monitoring of individuals. It can also help with calculating an APRI score.

DBST pathway

Orasure and cepheid pathway

Community guidelines for hepatitis C

From: Algorithm for accelerated treatment of hepatitis C, version 3. January 2020

On treatment monitoring of patients living with hepatitis C normally involves a baseline FibroScan and regular blood tests. In some settings this is not possible – a patient may be unable or unwilling to attend for testing. In most cases this should not preclude treatment as the benefit of eradicating hepatitis C and preventing hepatitis C-related liver disease and onward transmission will outweigh the risks. In cases of advanced liver disease, the risks are greater and where advanced liver disease is suspected treatment should be discussed with the appropriate local team (BBV team or hepatology team) prior to commencing treatment.

Below are two different algorithms based on whether or not testing can be performed.

When it is not possible to obtain venepuncture bloods or a FibroScan it will often be reasonable to proceed to treatment providing there are no concerns from a clinical perspective with regards to advanced liver disease (e.g. Child Pugh B or C cirrhosis) or other significant health problems.

Pan-genotypic treatment options for hepatitis C (Maviret [glecaprevir / pibrentasvir] and Epclusa [sofosbuvir / velpatasvir]) are extremely well tolerated with very few significant side effects. Information from the Summary of Product Characteristics (SmPC) documents the side effects of these medications, contraindications and other considerations of risk. In most patients, the benefit of treatment will outweigh the very minimal risks associated with these treatments, and as such treatment will often be appropriate even if the above preferred algorithm cannot be adhered to. Below is a suggested pathway for these individuals. Patients should be advised to attend for review if they become unwell whilst taking the medication and action taken accordingly.

Considerations

Hepatitis B Virus reactivation
Anyone who is sAg positive (current HBV infection) should be referred for advice and placed onto prophylactic therapy. Those who are sAg negative, cAb positive (past infection) should have their ALT monitored every month and tested for sAg and DNA if ALT increases.

Patients who failed a prior regimen containing an NS5A- and/or an NS3/4A-inhibitor
Resistance test needs to be carried out and the case discussed with BBV team.

Drug-drug interactions
Check Liverpool website (https://www.hep-druginteractions.org/). Refer to BBV team if unsure.

Use in diabetic patients
Diabetics may experience improved glucose control, potentially resulting in symptomatic hypoglycaemia, after initiating HCV direct acting antiviral treatment. Glucose levels of diabetic patients initiating direct acting antiviral therapy should be closely monitored, particularly within the first 3 months, and their diabetic medication modified when necessary. The physician in charge of the diabetic care of the patient should be informed when direct acting antiviral therapy is initiated.

Lactose
Maviret contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. Epclusa does not contain lactose.

Pregnancy
There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of glecaprevir or pibrentasvir in pregnant women. There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of sofosbuvir, velpatasvir or Epclusa in pregnant women.

Breastfeeding
It is unknown whether glecaprevir or pibrentasvir are excreted in human milk. It is unknown whether sofosbuvir, metabolites of sofosbuvir or velpatasvir are excreted in human milk.

Fertility
No human data on the effect of glecaprevir and/or pibrentasvir on fertility are available. No human data on the effect of Epclusa on fertility are available. Animal studies do not indicate harmful effects of sofosbuvir or velpatasvir on fertility.

Pathways

Algorithm 1: Preferred accelerated treatment algorithm to be used where possible

Algorithm 2: Accelerated treatment algorithm to be used where blood tests / FibroScan not possible

Change history

29 Apr 26

Published.

Cymraeg