Refined prediction of week 12 response and SVR based on week 4 response in HCV genotype 1 patients treated with peginterferon alfa-2a (40KD) and ribavirin.
OBJECTIVE
It is unclear whether the magnitude of reduction in hepatitis C virus (HCV) RNA between baseline and week 4 of treatment influences the probability of achieving a sustained virological response (SVR) in patients without a week 4 rapid virological response (RVR).


METHODS
Data were retrospectively analyzed from two studies in which treatment-naive patients received peginterferon alfa-2a (40KD) 180 μg/week plus ribavirin 1000/1200 mg/day for 48 weeks. Five hundred and fifty-eight genotype 1 patients with evaluable HCV RNA at baseline and week 4 were grouped according to RVR status: RVR (HCV RNA<50 IU/ml) or no RVR. Non-RVR patients were subdivided into discrete mutually exclusive categories according to week 4 HCV RNA; the proportion of patients with undetectable HCV RNA at week 12 was calculated per each category, and among them, the proportion with an SVR.


RESULTS
Overall, 88% of RVR patients and 43% of non-RVR patients achieved an SVR (p<0.0001). Among non-RVR patients, SVR rates were 77%, 61%, 43%, 27% and 13%, respectively (trend test p<0.0001) in those with unquantifiable HCV RNA or ≥ 3 log(10), ≥ 2 log(10), ≥ 1 log(10), or<1 log(10) drop to week 4. In patients HCV RNA positive at week 4, SVR rates were 67% for those negative at week 12 vs. 17% (HCV RNA positive patients or who had missing values at week 12 [p<0.0001]).


CONCLUSIONS
The probability of achieving SVR is graded in relation to the magnitude of reduction in HCV RNA at week 4 and 12. Patients with a ≥ 3 log(10) drop in HCV RNA at week 4 have a high probability of achieving an SVR.
Service d'Hepatologie and INSERM CRB3, University of Paris, Hopital Beaujon, Pavillon Abrami, 100 Boulevard General Leclerc, 92110 Clichy, France. patrick.marcellin@bjn.aphp.fr
Patrick
P
Marcellin
Nancy
N
Reau
Peter
P
Ferenci
Stephanos
S
Hadziyannis
Diethelm
D
Messinger
Fernando
F
Tatsch
Donald
D
Jensen
D000328:Adult; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011336:Probability; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage*
D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a