Pretreatment Predictive Factors for Hepatitis C Therapy Outcome: Relevance of Anti-E1E2 Antibodies Compared to Ip-10 and Il28B Genotypes
Autor: | Pascale Berthillon, Isabelle Chemin, Pierre Pradat, Clémence Arnaud, Martina Spaziante, Gloria Taliani, Marie-Anne Petit, Christian Trepo, Marianne Maynard |
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Rok vydání: | 2013 |
Předmět: |
Adult
Male Genotype Alpha interferon Pilot Projects Antiviral Agents Polymorphism Single Nucleotide Antibodies Polyethylene Glycols chemistry.chemical_compound Ribavirin medicine Humans Pharmacology (medical) Pharmacology Therapy Outcome biology business.industry Interleukins Interferon-alpha Interleukin Hepatitis C Hepatitis C Chronic Viral Load medicine.disease Recombinant Proteins Chemokine CXCL10 Treatment Outcome Infectious Diseases chemistry Immunology biology.protein RNA Viral Drug Therapy Combination Female Interferons Antibody Peptides business Viral load |
Zdroj: | Antiviral Therapy. 18:1027-1032 |
ISSN: | 2040-2058 1359-6535 |
DOI: | 10.3851/imp2671 |
Popis: | Background Unique serum anti-E1E2 antibodies were shown to be associated with spontaneous recovery or predictive of sustained virological response (SVR) in patients with chronic hepatitis C receiving pegylated interferon/ ribavirin (PEG-IFN/RBV) therapy. The objectives were to establish the relationship between pretreatment anti-E1E2 titres and HCV RNA kinetics during PEG-IFN/RBV therapy, and to examine whether the combined determination of interleukin (IL)28B rs12979860 and rs8099917, pretreatment inducible protein (IP)-10 levels and/or anti-E1E2 improved the prediction of SVR. Methods Sera from 26 treatment-naive consecutive HCV patients treated with PEG-IFN/RBV for 48 weeks were analysed. Serum anti-E1E2 titres and pretreatment IP-10 levels were measured by enzyme-linked immunosorbent assays. The IL28B variants were determined using genotyping real-time polymerase chain reaction method. Viral decline was measured at weeks (W) 4 and 12 and SVR assessed 6 months after the end of therapy. Results Baseline anti-E1E2 titres were correlated with HCV RNA decline at W4 and W12 and were highly predictive of SVR with 100% of patients negative for anti-E1E2 failing to achieve SVR. Receiver operating characteristic curve analyses indicate that the best prediction of SVR (AUC 0.990) was obtained with the combination of anti-E1E2 and IP-10 levels. Predictive values were better than those obtained with IP-10 alone or in combination with IL28B variants. Conclusions Pretreatment serum anti-E1E2 response predicts HCV RNA clearance kinetics and treatment outcome. The combination of anti-E1E2 and IP-10 significantly improved the prediction of treatment response. This warrants further investigation and validation on larger cohorts of patients in the context of new therapeutic strategies. |
Databáze: | OpenAIRE |
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