Is hepatitis C curable like 1

Hepatitis C: Therapy

In recent years, drugs with completely new modes of action have been developed. They intervene directly at different points in the replication cycle of the hepatitis C virus and are therefore referred to as substances with a direct antiviral effect (DAAs = Direct Acting Antivirals). Depending on the approach, a distinction is made between protease inhibitors, polymerase inhibitors and NS5A inhibitors as subgroups.

Eight modern DAAs are currently approved for the treatment of chronic hepatitis C across Europe. The DAAs contain one or more active substances (elbasvir / grazoprevir, daclatasvir, dasabuvir, ombitasvir / paritaprevir / ritonavir, simeprevir, sofosbuvir, sofosbuvir / ledipasvir, sofosbuvir / velpatasvir) and are administered individually or in combination. In addition, administration of ribavirin or, in some patients, administration of pegylated interferon alfa may be necessary. All DAAs are taken orally and are characterized by a favorable side effect profile.

Numerous studies have shown that by combining two or three of these new DAAs from different classes, a successful treatment of chronic hepatitis C is possible even without interferon. The choice of therapy depends on the genotype and stage of liver disease. The duration of therapy is usually twelve weeks. In some cases, it makes sense to shorten the therapy to eight weeks or to extend it to up to 24 weeks. All of the new DAAs mentioned are extremely effective against genotype 1. The cure rates are slightly lower for the other genotypes. Overall, cure rates of around 90 to 95 percent can usually be achieved, even with genotype 3, which is difficult to treat.

New therapy regimen for genotype 1

Since the modern DAAs mentioned are highly effective against genotype 1, there are currently four therapy regimes to choose from for treating this genotype:

  • Sofosbuvir + simeprevir
  • Sofosbuvir + daclatasvir
  • Sofosbuvir + ledipasvir
  • Paritaprevir / ritonavir + ombitasvir + dasabuvir

Numerous studies have shown that in patients in whom the liver still functions well, healing rates of over 95 percent can be achieved with all four therapy regimes with virtually no side effects. The combinations sofosbuvir + simeprevir or sofosbuvir + daclatasvir are, however, significantly more expensive than the other two schemes, so that they are currently not reimbursed by health insurance providers for genotype 1 therapy in Austria. Therefore, only the two other therapy regimes are described below.

  • Sofosbuvir + ledipasvir: The two active ingredients are combined in one tablet that must be taken once a day. For patients without liver cirrhosis who have never had treatment for chronic hepatitis C, eight weeks of therapy are sufficient. All other patients should be treated for twelve weeks.
  • Paritaprevir / ritonavir + ombitasvir + dasabuvir: Here three modern DAAs are combined with one another. Through the twelve-week administration of this so-called “3D regime”, cure rates of well over 90 percent could be achieved in patients with still good liver function. In some patient groups (especially genotype 1a), the additional administration of ribavirin is recommended.
  • Patients with decompensated liver cirrhosis: One speaks of decompensated cirrhosis of the liver when the organ can no longer compensate for the decline in function and thus can perform its tasks. If this is the case, not all modern DAAs can be unreservedly recommended: The two protease inhibitors simeprevir and paritaprevir are broken down in the liver, so that if the liver function is severely impaired, there is a risk of relevant side effects. In contrast, the NS5A inhibitors daclatasvir and ledipasvir and the polymerase inhibitor sofosbuvir do not cause any problems in this regard. In patients with decompensated cirrhosis of the liver, the combinations sofosbuvir + ledipasvir or sofosbuvir + daclatasvir have been studied best.

New therapy regimen for genotype 2

In patients with genotype 2, a twelve-week therapy with sofosbuvir + ribavirin can achieve virological cure rates of over 90 percent. In patients with cirrhosis of the liver, an extension of the therapy to 16 to 20 weeks should be considered. A very good, but more expensive alternative is the combination of sofosbuvir + daclatasvir for twelve weeks.

New therapy regimen for genotype 3

With the new DAA regimen, genotype 3 is the most difficult genotype to treat. The best therapy regimen currently is the combination of sofosbuvir + daclatasvir: With a twelve-week therapy, virological cure rates of over 95 percent were achieved in patients without liver cirrhosis. For patients with liver cirrhosis, however, a longer duration of therapy and / or the additional administration of ribavirin seems to be necessary. As an alternative to the combination of sofosbuvir + daclatasvir, a 24-week therapy with sofosbuvir + ribavirin or a twelve-week therapy with sofosbuvir + ledipasvir + ribavirin can be considered.

New therapy regimen for genotype 4

Essentially the same therapy regimes are available for genotype 4 as for genotype 1. The most important difference is that dasabuvir (due to lack of effectiveness against genotype 4) is omitted in the “3D regime” and paritaprevir / ritonavir + ombitasvir with ribavirin instead be combined.