Effect of ribavirin in genotype 1 patients with hepatitis C responding to pegylated interferon alfa-2a plus ribavirin.
OBJECTIVE
Pegylated interferon alfa-ribavirin combination is the standard treatment for chronic hepatitis C, but the mechanisms by which ribavirin enhances the rate of sustained hepatitis C virus (HCV) eradication remain unknown. We aimed to investigate the role of ribavirin in HCV clearance during therapy and to evaluate the consequences of ribavirin discontinuation in patients infected with genotype 1 hepatitis C who cleared HCV RNA at week 24.


METHODS
A total of 516 patients were treated with pegylated interferon alfa-2a, 180 microg/wk, plus ribavirin, 800 mg/day. Seventy percent were RNA negative at week 24. They were randomized to continue with the combination or receive pegylated interferon alone.


RESULTS
Responders at week 24 who stopped ribavirin had a significantly higher rate of breakthroughs during, and relapses after, therapy (sustained virologic response, 52.8% vs 68.2%; P = .004), but their side-effect profile and quality of life tended to improve. Multiple logistic regression analysis in the pegylated interferon alfa monotherapy group allowed identification of responders at week 24 who could stop ribavirin without losing their chance of a sustained virologic response, based on baseline viral load and age. Forty-eight weeks of ribavirin may not be needed when HCV RNA is undetectable at week 2.


CONCLUSIONS
We made 3 conclusions from this study. First, ribavirin primarily acts by sustaining the virologic response to pegylated interferon alfa; second, ribavirin must be administered for the full treatment duration in most genotype 1-infected patients who respond; third, baseline parameters may help identify patients who could discontinue ribavirin or reduce the dose without losing their chance of success.
Bronowicki
Jean-Pierre
JP
Department of Hepatology and Gastroenterology, INSERM U724, CHU de Nancy, Vandoeuvre-les-Nancy, France.
Ouzan
Denis
D
Asselah
Tarik
T
Desmorat
Hervé
H
Zarski
Jean-Pierre
JP
Foucher
Juliette
J
Bourlière
Marc
M
Renou
Christophe
C
Tran
Albert
A
Melin
Pascal
P
Hézode
Christophe
C
Chevalier
Michelle
M
Bouvier-Alias
Magali
M
Chevaliez
Stéphane
S
Montestruc
François
F
Lonjon-Domanec
Isabelle
I
Pawlotsky
Jean-Michel
JM
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005221:Fatigue / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; 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* / Q000009:adverse effects; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D011788:Quality of Life; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D000410:Alanine Transaminase; C100416:peginterferon alfa-2a