There is a growing group of people who have failed to clear the virus after one or more rounds of interferon based treatment. Someone who relapses after treatment (a relapser) is defined as having achieved a sustained virologic response (SVR) during the course of treatment but in whom the virus was again detectable during the three or six month follow up period. For people who relapse after treatment the variations in dosage and length of interferon based treatments below offer some chance of clearing the virus.
Amongst those people who do not achieve SVR there are two categories and it is important to differentiate between them.
- The first group are nil responders. Those who do not show an appreciable decline in HCV RNA during treatment. These people can be recognised within 12 weeks of starting peg-interferon/ribavirin therapy as they do not achieve a 2 log reduction from the level at the start of treatment after 12 weeks. Continued treatment of these nil responders rarely results in further decline in viral load and there is not much point in continuing the treatment.
- The second group are partial responders. These are people who have an early virologic response. Their HCV RNA drops more than 2 logs from the level at the start of treatment within the first 12 weeks, but then slows down or evens out. This group of partial responders have a better chance of responding and achieving SVR during retreatment than nil responders. This group also have some chance of achieving SVR if treatment is extended to 72 weeks.
It is now known that there are a number of factors involved with a decreased chance of clearing the virus.
- Genotype 1
- Failure to respond to treatment by week 12
- Cirrhosis
- A high viral load
- Older age
- Length of infection
- Obesity
- Poor adherhance to the treatment drugs
- Afro/Caribbean
- HIV co-infection
- Immunosuppressant treatment following liver transplantation
For people who have not responded to standard (non-pegylated) interferon therapy without ribavirin there is about a 30% chance of a SVR when they are treated with pegylated interferon and ribavirin. However, for those people who have failed to respond to standard (non-pegylated) interferon plus ribavirin the rate of SVR is only 10-20%. For people who have not responded to pegylated interferon and ribavirin the options are more limited.
b. Ribavirin with Erythropoietin (Epoetin)
Anaemia is the most problematic side effect of ribavirin. It can often lead to the need to reduce the dose or abandon treatment with ribavirin altogether. The use of the drug epoetin in conjunction with peg-interferon and high doses of ribavirin has been shown to reduce anaemia and the need for ribavirin dose reductions, which in turn leads to higher SVRs. In a study evaluating high dose ribavirin with epoetin it was found that patients who received high dose ribavirin had a significant increase in SVR over those receiving the standard dose, from 34% to 49%. This increase in SVR was the result of a marked reduction in the incidence of relapse, dropping from about 36% to 9%.
Recent studies have also indicated that high doses of ribavirin with epoetin increases SVR in people with genotype 1.
