title: What to do when standard therapy fails.
abstract: 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.
authors.affiliation: University General Hospital Valle de Hebron, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Buti
authors.forename: R
authors.initials: R
authors.lastname: Esteban
mesh_terms: D000547:Amantadine / Q000008:administration & dosage / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D004338:Drug Combinations; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000008:administration & dosage / Q000627:therapeutic use; D008017:Life Expectancy; D008103:Liver Cirrhosis / Q000821:virology; D012367:RNA, Viral / Q000235:genetics; D012074:Remission Induction; D019233:Retreatment; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D012307:Risk Factors; D013997:Time Factors; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004338:Drug Combinations; D012367:RNA, Viral; D012254:Ribavirin; D007372:Interferons; D000547:Amantadine