The end-of-treatment ribavirin concentration predicts hepatitis C virus relapse.
BACKGROUND
The optimization of combination therapy with ribavirin (RBV) and pegylated interferon alpha has substantially improved sustained virologic response (SVR) rates and lowered virologic relapse rates in patients infected with hepatitis C virus (HCV). In this study, we performed an analysis of the relationship between the end-of-treatment plasma RBV concentration and virologic relapse.


METHODS
Thirty-four patients with HCV treated with pegylated interferon/RBV and with an end-of-treatment response were assayed for plasma RBV concentration using liquid chromatography assay coupled to tandem mass-spectrometric detection on the last day of the treatment. Clinical data and the concentration of RBV were compared between patients classified as either relapsers or nonrelapsers.


RESULTS
Eleven patients (32.4%) relapsed and 23 patients (67.6%) achieved an SVR. The mean plasma RBV concentration on the last day of treatment was 1380 ± 312 ng/mL for relapsers and 2278 ± 569 ng/mL for SVR patients (P < 0.0001). A receiver operating characteristic analysis showed that a threshold of 1960 ng/mL was associated with the greatest sensitivity and specificity (100% and 83%, respectively, with an area under the curve of 0.94; P < 0.0001) for discriminating between patients who relapsed and those who did not. A univariate logistic regression analysis indicated that a plasma RBV concentration of <1960 ng/mL at the end of the treatment was strongly associated with relapse (odds ratio, 55; 95% confidence interval, 7.24-∞; P = 0.0001) independently of age, body weight, RBV dose, baseline viral load, the interleukin-28B genotype, and response to previous courses of treatment.


CONCLUSIONS
Our study results highlight the relevance of measuring plasma RBV concentrations during and at the end of HCV treatment, with a view to avoiding virologic relapse.
*Departments of Pharmacology and †Virology, Amiens University Medical Center; ‡Virology Research Unit, EA 4294, Jules Verne University of Picardie; and §Department of Hepatogastroenterology, Amiens University Medical Center, Amiens, France.
Sandra
S
Bodeau
Charlotte
C
Durand-Maugard
Anne-Sophie
AS
Lemaire-Hurtel
Catherine
C
François
Sandrine
S
Castelain
François
F
Helle
Michel
M
Andréjak
Eric
E
Nguyen-Khac
Gilles
G
Duverlie
Etienne
E
Brochot
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D019540:Area Under Curve; D002853:Chromatography, Liquid / Q000379:methods*; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012008:Recurrence; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods; D013997:Time Factors; D016896:Treatment Outcome
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a