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Dysregulation of IFN System Can Lead to Poor Response to Pegylated Interferon and Ribavirin Therapy in Chronic Hepatitis C
- Source :
- PLoS ONE, Vol 6, Iss 5, p e19799 (2011), PLoS ONE
- Publication Year :
- 2011
- Publisher :
- Public Library of Science (PLoS), 2011.
-
Abstract
- Background Despite being expensive, the standard combination of pegylated interferon (Peg-IFN)- α and ribavirin used to treat chronic hepatitis C (CH) results in a moderate clearance rate and a plethora of side effects. This makes it necessary to predict patient outcome so as to improve the accuracy of treatment. Although the antiviral mechanism of genetically altered IL28B is unknown, IL28B polymorphism is considered a good predictor of IFN combination treatment outcome. Methodology Using microarray, we quantified the expression profile of 237 IFN related genes in 87 CH liver biopsy specimens to clarify the relationship between IFN pathway and viral elimination, and to predict patients' clinical outcome. In 72 out of 87 patients we also analyzed IL28B polymorphism (rs8099917). Principal Findings Five IFN related-genes (IFI27, IFI 44, ISG15, MX1, and OAS1) had expression levels significantly higher in nonresponders (NR) than in normal liver (NL) and sustained virological responders (SVR); this high expression was also frequently seen in cases with the minor (TG or GG) IL28B genotype. The expression pattern of 31 IFN related-genes also differed significantly between NR and NL. We predicted drug response in NR with 86.1% accuracy by diagonal linear discriminant analysis (DLDA). Conclusion IFN system dysregulation before treatment was associated with poor IFN therapy response. Determining IFN related-gene expression pattern based on patients' response to combination therapy, allowed us to predict drug response with high accuracy. This method can be applied to establishing novel antiviral therapies and strategies for patients using a more individual approach.
- Subjects :
- Male
Microarrays
Gastroenterology and hepatology
Gene Expression
lcsh:Medicine
Genome-wide association study
medicine.disease_cause
Hepatitis
Polyethylene Glycols
chemistry.chemical_compound
Pegylated interferon
Treatment Failure
Precision Medicine
lcsh:Science
Lead (electronics)
Multidisciplinary
Interleukin
Genomics
Middle Aged
Prognosis
Hepatitis C
Recombinant Proteins
Infectious hepatitis
Treatment Outcome
Medicine
Infectious diseases
Drug Therapy, Combination
Female
Research Article
medicine.drug
Drugs and Devices
Drug Research and Development
Hepatitis C virus
Alpha interferon
Viral diseases
Interferon alpha-2
Biology
Antiviral Agents
Molecular Genetics
Predictive Value of Tests
Ribavirin
Genetics
medicine
Humans
Genetic Association Studies
Liver diseases
Aged
Clinical Genetics
Polymorphism, Genetic
Gene Expression Profiling
Interleukins
lcsh:R
Computational Biology
Interferon-alpha
Human Genetics
Hepatitis C, Chronic
Gene Expression Regulation
chemistry
Pharmacogenetics
Immunology
lcsh:Q
Interferons
Genome Expression Analysis
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....9a98d3c679cd424df0c9120b7155e255