Antiviral effect of ribavirin in early non-responders to interferon monotherapy assessed by kinetics of hepatitis C virus RNA and hepatitis C virus core antigen.
OBJECTIVE
To evaluate the efficacy of ribavirin, given in second intention in non-responders to interferon alone, by studying viral kinetics.


METHODS
We conducted a trial including 203 patients with chronic hepatitis C, naïve of treatment. Patients were treated with interferon three times a week with or without ribavirin and amantadine according to response. Viral kinetics were assessed by serial measurements of HCV RNA (bDNA 3.0 and Monitor 2.0) and a new assay, trak-C, able to quantify total Hepatitis C virus (HCV) core antigen.


RESULTS
A significant initial drop in HCV RNA or HCV core antigen, under interferon alone, was associated with response to therapy, -4.85+/-1.33 log for HCV RNA in sustained responders versus -1.86+/-1.53 log for others groups, P<0.001. In patients receiving ribavirin in second intention, we also observed a similar drop in HCV RNA and HCV core antigen, predictive of sustained response, -2.67+/-1.26 log for HCV RNA in sustained responders versus -0.44+/-0.49 log in non-responders, P<0.001.


CONCLUSIONS
Ribavirin has probably an additional antiviral effect in interferon treated patients. Kinetics of HCV RNA and HCV core antigen under treatment are highly predictive of a sustained virological response.
Lunel
Françoise
F
Laboratoire de Bactériologie-Virologie, CHU Angers, Angers Cedex, France. frlunel-fabiani@chu-angers.fr
Veillon
Pascal
P
Fouchard-Hubert
Isabelle
I
Loustaud-Ratti
Véronique
V
Abergel
Armand
A
Silvain
Christine
C
Rifflet
Hervé
H
Blanchi
Alain
A
Causse
Xavier
X
Bacq
Yannick
Y
Payan
Christopher
C
D000328:Adult; D000547:Amantadine / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D018936:Hepatitis C Antigens / Q000097:blood; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D019233:Retreatment; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D014758:Viral Core Proteins / Q000097:blood; D019562:Viral Load
D000998:Antiviral Agents; D018936:Hepatitis C Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D014758:Viral Core Proteins; D012254:Ribavirin; D000547:Amantadine