Predicting the therapeutic response in patients with chronic hepatitis C: the role of viral kinetic studies.
A substantial proportion of patients infected with hepatitis C virus (HCV) genotype 1 still does not respond to pegylated interferon-alfa/ribavirin (IFN/RBV) therapy. Factors which identify potential non-responders are needed to limit exposure to drugs in patients unlikely to benefit from treatment and to save health care resources. Host predictive factors have a low negative predictive value. In contrast, viral factors have a high precision in predicting outcome of therapy. Viral kinetics are the basis for the study of response of therapy. The decrease in viral load within 24 h after administration of a single test dose of conventional IFN reflects the IFN-sensitivity of the virus strain and predicts the outcome of conventional IFN/RBV therapy even before treatment with a specificity of 100% and a sensitivity of 83%. In contrast to conventional IFN, the two available PEG-IFN preparations differ considerably in how they suppress viral replication, and cut-off values have to be prospectively established separately for each drug. Patients without an early virological response (HCV-RNA either undetectable or decrease by >or=2 log10 after 12 weeks) (EVR), do not achieve a sustained virological response (SVR; negative predictive value: 97-98%). Thus, in the absence of an EVR, treatment should be stopped. The outcome of PEG-IFN alfa-2a/RBV combination therapy is dependent on the rapidity of the virological response. Patients who become HCV-RNA negative after 4 weeks have the best chance of achieving an SVR. The rapidity of viral elimination may be a useful guide to tailoring the length of treatment in patients with an EVR.
Ferenci
Peter
P
Department of Internal Medicine IV, Gastroenterology and Hepatology, University of Vienna, Waehringer Guertel 18-20, A 1090 Vienna, Austria. peter.ferenci@akh-wien.ac.at
D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000187:drug effects*; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D007700:Kinetics; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D011379:Prognosis; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a