The process of initiating treatment is simple:
- Genotype by looking it up or ordering HCV Genotype
- Fibrosis by fibroscan or APRI* or Fibrosure or Hepascore or ELF score or biopsy
- Past Treatment for HCV
- Hepatitis B status
These are the key items that determine which medications are appropriate and the required duration of treatment. Patients in the USA can order these tests privately via Link2labs. Please follow this Link2Labs link for our page on specific details.
* The APRI score is calculated from the platelets of the full blood count and AST from the liver panel meaning most patients already have this available. The APRI can be calculated from these values here and a value < 1 suggests cirrhosis is not present and 12 weeks treatment will be long enough.
The quickest way to make an accurate evidence-based prescription is to use our HCV Decision Support Tool which can be found here, just by adding 'hcv' to the end of the URL http://fixhepc.com/hcv
Simply fill in the requested values, select the guidelines you wish to use and press calculate. The tool will automatically convert APRI, kPA, Hepascore or ELF score values to the F0-F4 fibrosis scale. Not only will you get a precise list of prescription options, they are sorted by expected SVR (Sustained Virological Response aka Cure) rate. You can print these out or save to a PDF for your records. The show trials button will show you all the trials on which these recommendations are based.
Alternatively, you can refer to the treatment guidelines below where you will also use the 3 items - genotype, fibrosis, and past treatment - described above:
These guidelines will often provide several possibilities so we need to look for reasons to favour one option over the others (if there are options)
- Drug interactions need to be checked, and this is the best tool http://www.hep-druginteractions.org/checker. It produces PDF reports to save in the patient's record.
- Severe renal or liver disease that may contraindicate certain medications or require dose adjustment
- Blood results indicating anaemia or thrombocytopenia that say NO ribavirin
- Hep B reactivation has been reported in patients with chronic Hep B (see below)
This is 100% medico-legally defensible - Yes, your honour, I chose to prescribe proven generic Hep C medications to a Hep C patient. This decision was entirely appropriate, done according to established guidelines, and with full patient informed consent.
You should inform patients that at some point in the future these medications will be available (effectively for free) via your local subsidy process (like what happened in Australia). The vast majority will say they are either sick of waiting or can't afford to wait, but they should be informed.
Hepatitis B reactivation
Patients with chronic Hepatitis B are at risk of reactivation when they are cleared of HCV with DAAs. These patients should either be closely monitored of offered 1 year of prophylactic Entecavir or Tenofovir. Here is a quick refresher on Hep B
- Patients who are HBV surface antibody negative and HBV core antibody negative have never been exposed to Hep B and are not immune due to vaccination, however, they have no risk of reactivation (only of primary infection with Hep B).
- Patients who are HBV surface antibody positive are immune, regardless of whether that is from immunisation or past infection, and have no risk of reactivation.
- Patients who are HBC core antibody positive have been exposed to Hep B and have chronic Hep B unless their surface antibody is positive, so patients who are HBVsAb -ve and HBVcAb +ve are at risk (low risk).
- Patients who have active Hep B will have HBVsAb -ve, HBVcAb +ve as well as a positive HBV surface Antigen and PCR DNA viral load. THESE PATIENTS ARE HIGH RISK.
|HBVsAb||HBVcAb||HBVsAg||HBV PCR DNA||Interpretation|
|-ve||-ve||Not required||Not required||Never exposed, no risk|
|+ve||-ve||Not required||Not required||Immunised, immune, no risk|
|+ve||+ve||Not required||Not required||Exposed, immune, no risk|
|-ve||+ve||-ve||-ve||Chronic, incactive, real but low risk|
|-ve||+ve||+ve||+ve||Chronic, active, high risk|
Accessing Generic Medications
Helping the patient safely access these medications completes your duty of care around making a prescription.
Treatment length is generally 12 weeks, so 84 days. The bottles contain 28 tablets, so there are 3 bottles in a 12 week course. For cirrhotics it is often 24 weeks, so 168 days. Ribavirin can be used in some cases to shorten the required treatment duration and save patient cost at the expense of Ribavirin side effects.
Here are the common 12 week prescriptions for generics with their branded names:
- Sofosbuvir 400mg / Ledipasvir 90 mg, one tablet oral daily x 84 (Generic Harvoni® in a single tablet)
- Sofosbuvir 400mg + Daclatasvir 60 mg, one tablet oral daily x 84 (Generic Sovaldi® and Daklinza® each in their own tablet)
- Sofosbuvir 400mg / Velpatasvir 100mg, one table oral daily x 84 (Generic Epclusa® in a single tablet)
Now the patient has access to the medications, here is what monitoring on treatment looks like:
- Baseline FBC, Cr&E, LFTs, Hep C Viral Load with reasonable currency + AFP and liver ultrasound for those with cirrhosis looking for Hepato-Cellular Carcinoma (HCC).
- 4/52 into treatment FBC, Cr&E, LFTs, Hep C Viral Load.
- Repeat Viral Load at 4 week intervals, if not undetected 4 weeks after commencing treatment (once undetected there is little value in repeating unless virological breakthrough seems likely - LFT elevations will flag this).
- EOT (End Of Treatment) exit bloods.
Hep C Viral Load can be quantitative (undetectable, <15, or 15-100,000,000) or qualitative (undetected/detected). Quantitative makes sense early on in treatment, but once <15 has no extra value over a qualitative detected/undetected.
In Australia, Medicare will pay for 2 quantitative and 4 qualitative tests a year. Note that Medicare will only fund Hep C viral load testing when it is a) ordered by a specialist or b) ordered by a GP for a patient having treatment, so please make sure you add "Having DAA treatment for HCV" in the clinical notes or your patient will get either a bill or the test won't get done.
Typical side effects are listed on the DAA treatment side effects page.
With headache and insomnia being relatively common, know that aspirin, paracetamol and ibuprofen, morphine, methadone and tramadol all work for headache and don't interact. For insomnia temazepam, diazepam, oxazepam and zolpidem all work and don't interact.
For answers to typical patient questions please consult our Frequently Asked Questions section.
The typical treatment experience is usually very favourable. No, or minimal side effects with many patients and by week 4, feeling better than they have in years.
Ribavirin is a different kettle of fish. It is a fake guanosine, so gets incorporated in all DNA/RNA, with the result it impacts on all dividing cells as well as the Hep C virus. Anaemia is a common side effect. Dose reduction or cessation may be required. The dose is 1000 mg if < 75 kg and 1200 mg if > 75 kg daily in two divided doses. Reduction by one or two 200 mg capsules a day is a reasonable first response to falling Hb or platelets. Frequent monitoring (fortnightly) will catch ADRs like anaemia before they become a major problem. Asymptomatic changes to the numbers do not warrant concern.
Ribavirin is a booster so don't avoid it because it needs more monitoring. Your patients will get better results if it is prescribed as per guidelines than if not. It is generally only required in patients with cirrhosis.
SVR (Sustained Virological Response)
Treatment success rate is about 90-95% and is measured with SVR. SVR is counted in weeks from the cessation of medication.
- SVR24 is the gold standard - zero viral load at 24 weeks post treatment and represents a < 0.1% chance of ever seeing the virus again
- SVR4 represents a 95% chance of making SVR24
- SVR12 represents a 99.7% chance of making SVR24
Hep C Ab (Antibody) Levels versus Hep C RNA
When a person clears the virus, HCV RNA will not be detectable. This is reported as HCV RNA Not Detected.
Hep C Antibody levels fall over time but patients who have been cured will continue to test positive for Hep C Antibodies for years. A positive Antibody test is thus normal and does not say anything about the current status of the disease, only a test for HCV RNA can answer the question about recurrence and if the virus has returned.
Sustained virological response is associated with clearance of hepatitis C virus RNA and a decrease in hepatitis C virus antibody.
Cirrhosis and Fibrosis
There is good evidence for regression of fibrosis at SVR.
SVR After Therapy Reduced Inflammation, Fibrosis in HCV Patients
Patients with cirrhosis should be monitored every 6 months for Hepatocellular Carcinoma. While the AFP test is a guide, it is possible they have an HCC with a normal AFP. Ultrasound, triple phase CT, or MRI are all good ways to look for HCC.
PATIENTS WITH CIRRHOSIS AND WHO HAVE HAD A PRIOR HCC NEED VERY CLOSE MONITORING as recent studies have suggested an unusually high rate of HCC recurrence in this population post DAA therapy.
DAAs have minimal side effects on treatment and offer an excellent prospect of cure.
Patients can continue to work while being treated and typically feel better within a week.
DAAs are low risk to prescribe and patients are grateful for your help.
If you are a doctor interested in offering this service to your patients or would like to help manage patients through their online (video) platform please contact GP2U. GP2U has high paying sessional work available that can be done from your practice, home or anywhere with a good internet connection.
If this page has been printed you can access the online version at: http://fixhepc.com/gp