PEG-interferon & ribavirin have been the mainstay of hepatitis C therapy for the last decade, with the addition in the last few years of the first direct-acting antiviral drugs (DAAs), telaprevir and boceprevir, for genotype 1 infections. These drug regimes have led to cure for many patients, but have been unsuccessful in many, and have been poorly tolerated. Many patients have been unwilling to have treatment due to fear of side effects.
A new era in interferon-free therapy is coming, with new DAAs showing great promise, with very high cure rates and minimal side effects in trials. New treatment regimes will typically be one daily dose, taken orally, for between 12 and 24 weeks, with even shorter regimes showing promise. The first drugs have been approved in various countries, and sofosbuvir and simeprevir are already in widespread use in the USA. The timing of availability of new drug regimes in Australia is unclear, with concerns that the high cost of these drugs will limit availability.
This uncertainty makes treatment decisions difficult, as undoubtedly the new DAA regimes will be more effective and much better tolerated than existing therapy. The duration of therapy will often be much shorter in the future. Interferon-free therapy appears likely to be successful in difficult-to-treat patients such as decompensated cirrhotics, post liver transplant, HIV co-infection and non-responders to previous therapy.
The current challenge is to identify patients who should be treated now. Our aim should be to treat those patients at most risk of adverse outcomes without treatment, and should aim to identify patients with advanced fibrosis or early cirrhosis.
The Lismore Liver Clinic now has a Fibroscan machine, which allows non-invasive assessment of liver stiffness, a reasonable proxy for fibrosis. The patient experience is similar to having an ultrasound. The results are generally reliable for high & low scores, with good prediction of high and low fibrosis scores. Intermediate results are less useful.
Other non-invasive tests are available. ARFI is another technique to measure liver stiffness, but uses a conventional ultrasound machine (only available in some radiology practices). Various panels of serum markers are available. SNP pathology now offers an enhanced liver fibrosis score (ELF), which is also reliable for high & low scores, with a significant intermediate range. All non-invasive tests attempt to assess liver fibrosis without the need for liver biopsy.
Patients who appear likely to have advanced fibrosis should be assessed for immediate treatment. All patients should be advised to modify lifestyle factors known to hasten fibrosis progression - avoid excessive alcohol consumption, daily cannabis use and obesity/ metabolic syndrome.
Trials reported at EASL 2014 showing excellent results, with associated pharmaceutical company:
- Gilead: Genotype 1-6 for sofosbuvir and GS-5816, ledipasvir mainly active against G1
- AbbVie: 3D (ABT-450/r/ABT-267 + ABT-333): G1 and G4, plus ribavirin
- Merck/MSD: MK-5172, MK-8742 G1 with ribavirin
- BMS: dalcatasvir, asunaprevir and BMS-791325 G1-4
- Janssen: simeprevir – G1, used with PEG-INF, ribavirin and Gilead’s sofosbuvir