Virological response at 4 weeks to predict outcome of hepatitis C treatment with pegylated interferon and ribavirin.
BACKGROUND
Viral kinetics during therapy provides information on how to individualize treatment. To determine the benefit of assessing positive predictive values (PPVs) and negative predictive values (NPVs) of rapid virological responses (RVRs) and early virological responses (EVRs), on-treatment outcomes in chronic hepatitis C patients were examined.


METHODS
A total of 408 patients (221 treatment-naive) treated with pegylated interferon-alpha2b and ribavirin were included. Hepatitis C virus (HCV) RNA was measured at baseline, 4 weeks and 12 weeks. RVR was defined as undetectable HCV RNA at 4 weeks and EVR as >/=2 log(10) decrease in HCV RNA at 12 weeks. The additive value of RVR on predicting sustained virological response (SVR) was assessed with receiver operating characteristic (ROC) curves.


RESULTS
SVR, RVR and EVR were observed in 46%, 23% and 78% of patients, respectively. PPVs of RVR were 96%, 100% and 100% in treatment-naive patients, relapsers and non-responders, respectively. NPVs of failure to achieve EVR were 97%, 75% and 91%, in treatment-naive patients, relapsers and non-responders, respectively. At 4 weeks, patients with RVR had the highest probability to achieve SVR (odds ratio 44.98 in the entire population and 32.95 in treatment-naive patients). ROC curves showed the area under the ROC curve to be 0.758 versus 0.832 in the entire population and 0.795 versus 0.858 in treatment-naive patients at baseline versus week 4, respectively.


CONCLUSIONS
RVR is a strong predictor of SVR (PPV>96%) and failure to achieve EVR is a strong predictor of non-SVR (NPV>75%), independent of patients' pretreatment status. Added to baseline characteristics, RVR increased the accuracy to predict SVR. The combination of RVR and EVR provided complementary information, and thus provides a key opportunity to individualize treatment and improve the benefit/risk ratio of therapy.
Martinot-Peignoux
Michelle
M
INSERM, U-773, Centre de Recherche Biomédicale Bichat-Beaujon CRB3, Université Paris VII, Hôpital Beaujon, Clichy, France.
Maylin
Sarah
S
Moucari
Rami
R
Ripault
Marie-Pierre
MP
Boyer
Nathalie
N
Cardoso
Ana-Carolina
AC
Giuily
Nathalie
N
Castelnau
Corinne
C
Pouteau
Michàle
M
Stern
Christiane
C
Aupérin
Anne
A
Bedossa
Pierre
P
Asselah
Tarik
T
Marcellin
Patrick
P
D000998:Antiviral Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000097:blood*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b