What to do when standard therapy fails.

An important group of patients with chronic hepatitis C do not respond to interferon (IFN) therapy. Compared with untreated patients with chronic hepatitis C, non-responders have a higher percentage of cirrhosis, are more frequently infected by genotype 1 and usually have a viral load above 2 x 106 copies/ml. Also, patients with cirrhosis have lower life expectancy and higher risk of clinical complications, and therefore, are most in need of effective treatment strategies. There is no evidence that the re-treatment of non-responders with a standard regimen of IFN or more prolonged IFN therapy achieves a sustained biochemical or virological response. Between 20% and 40% of non-responder patients treated with IFN therapy for more than two years had an hepatic improvement in liver histology associated with a decrease in hepatitis C virus-ribonucleic acid levels. In contrast, combination therapy with IFN and ribavirin for six months now results in sustained response rates between 6% and 29% depending on the viral genotype and the presence or absence of cirrhosis. Patients infected with genotype 2 and 3 have a higher probability of achieving a sustained virological response than those infected by genotype 1. Currently, different studies are underway to determine whether high-dose IFN and/or induction therapy combined with ribavirin for more prolonged periods of time could increase the sustained response rate in non-responders. No other drugs appear to be efficacious in these patients, except the combination of IFN, ribavirin and amantadine which has shown interesting results in a preliminary trial but they need to be confirmed in further studies. These findings suggest that combination therapy is beneficial and can be recommended for some non-responder patients until other new therapies are available.