Hepatitis C Treatment

There has been a huge amount of drug development in hepatitis C with many new drugs launched in the last two years. Whereas hepatitis C treatment used to consist of ribavirin and interferon, generally in the pegylated, longer-lasting form, which boosts the body’s own immune system, most of the new drugs work differently, attacking the virus itself. They primarily target one of three distinct parts of the virus called the protease, the polymerase and the NS5A area and are therefore known respectively as protease inhibitors, polymerase inhibitors and NS5A inhibitors. Collectively they are known as Direct Acting Antivirals (DAAs). Initially used with interferon, they are now being increasingly used in combination with each other and without interferon. This is allowing much shorter courses of treatment, 12 weeks or less, with fewer, more tolerable side effects.

The aim of treatment for hepatitis C is achieve a Sustained Virological Response (SVR), meaning that the virus is not detectable in blood originally 24 weeks, now more frequently 12 weeks, after treatment has stopped. This is the equivalent of a cure because the virus does not return, unless the person is newly infected. The new drugs are showing SVR rates of approaching 100% in trials. However this depends on which combination is used, how much liver damage the patient has, with those with cirrhosis generally doing less well, and also on genotype. Whereas genotype 1 was considered the hardest to treat successfully with interferon, genotype 3 seems to be the hardest with the new drugs and we have very little data on genotypes 5 and 6. However, new drugs that will work equally across all genotypes are in trials.

One of the most exciting aspects of the new drugs is that in the absence of interferon they appear to be safe enough to use on people who have decompensated cirrhosis, offering them the chance both of a cure and an improvement in their condition, perhaps no longer needing a transplant.

The new drugs are expensive in the developed world and in some countries this is limiting their use. Many governments are currently in discussions with the manufacturers to secure lower prices. In the developing world, some manufacturers have already announced ‘access programmes’ and the others will undoubtedly follow. These programmes generally involve significantly lower prices and sometimes licensing agreements with generic manufacturers. So far Gilead and BMS have announced access programmes. You can view the Gilead access programme here. Aside from the discussions over price, access to the drugs is slowed by the time it takes to license and/or register them. What is available and at what price is therefore currently different and changing in each country.

The World Health Organization has launched Guidelines for the screening, care and treatment of persons with hepatitis C infection, which set out who should be treated and with what drugs. This will be regularly updated as new drugs become available.

Examples of the DAAs currently available in at least some countries are:

Protease inhibitors (names end in –previr)

  • First generation: 
  • Boceprevir
  • Telaprevir, 

Second generation (better and with fewer side effects):

  • Asunaprevir
  • Paritaprevir
  • Simeprevir

Polymerase inhibitors (names end in –buvir)

  • Dasabuvir
  • Sofosbuvir

NS5A inhibitors (names end in –asvir)

  • Daclatasvir
  • Ledipasvir
  • Ombitasvir

Common Combinations marketed by a single manufacturer

  • Harvoni – Sofosbuvir and Ledipasvir
  • ‘3D’ – Paritaprevir, Dasabuvir and Ombitasvir