Serum proteome to predict virologic response in patients with hepatitis C treated by pegylated interferon plus ribavirin.
OBJECTIVE
Surface-enhanced laser desorption ionization time-of-flight mass spectrometry is a proteomic technique that enables the global profiling of proteins. We used this approach to monitor the kinetics of serum proteome in patients with chronic hepatitis C virus infection receiving a standard bitherapy regimen to predict treatment response.


METHODS
Ninety-six patients with chronic hepatitis C were retrospectively selected. All patients received complete treatment with pegylated interferon in combination with ribavirin. Patients had serum sampling before starting treatment and at the end of treatment. Results were validated in an independent cohort of 51 patients.


RESULTS
Comparison of protein profiles in pretreatment and after-treatment serum allowed us to characterize 50 protein peaks, the level of which significantly varied. In the group of patients with sustained virologic response, 37 peaks displayed significant variation during treatment, whereas only one peak differed in nonresponders. A logistic regression analysis allowed us to define an algorithm composed of 2 protein peaks (fibrosis stage and genotype) that correctly predicted, in pretreatment serum, response to treatment in 89% of all patients with an area under the receiver operating characteristic curve of 0.92. In the independent testing group, the same difference in proteome kinetics was observed between sustained responders and nonresponders. The algorithm correctly predicted treatment response in 81% of patients in the testing group.


CONCLUSIONS
This study suggests that the kinetics of proteome are significantly different in serum of patients according to treatment response. Serum protein profiling allows prediction of response to antiviral treatment in a significant proportion of patients.
Paradis
Valérie
V
Service d'Anatomie Pathologie, Hôpital Beaujon, and CNRS UMR 8149, Clichy, France. vparadis@teaser.fr
Asselah
Tarik
T
Dargere
Delphine
D
Ripault
Marie-Pierre
MP
Martinot
Michèle
M
Boyer
Nathalie
N
Valla
Dominique
D
Marcellin
Patrick
P
Bedossa
Pierre
P
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage*; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D005819:Genetic Markers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D020543:Proteome; D011994:Recombinant Proteins; D012254:Ribavirin