Peripheral Blood Gene Expression Profile Associated with Sustained Virologic Response after Peginterferon Plus Ribavirin Therapy for Chronic Hepatitis-C Genotype 1

• Published in: Journal of the National Medical Association Vol. 100; no. 12; pp. 1425 - 1433
• Main Authors: Huang, Chao, MS, Chen,, Hegang, PhD, Cassidy,, William, MD, Howell,, Charles D., MD
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.12.2008; National Medical Association; Elsevier Limited
• Subjects: Adult; Biological and medical sciences; Female; Gene Expression Profiling; General aspects; genetics; Genotype; Hepacivirus - genetics; hepatitis; Hepatitis C - drug therapy; Hepatitis C - genetics; Human viral diseases; Humans; Infectious diseases; Interferon alpha-2; Interferon-alpha - administration & dosage; Internal Medicine; Leukocytes, Mononuclear - metabolism; Male; Medical sciences; Middle Aged; Oligonucleotide Array Sequence Analysis; Polyethylene Glycols - administration & dosage; Polymerase Chain Reaction; Recombinant Proteins; Ribavirin - administration & dosage; RNA, Viral - blood; Treatment Outcome; Viral diseases; Viral hepatitis; hepatitis; genetics; Drug combination; Typing; Hepatic disease; Genotype; Ribavirin; Blood; Gene expression profile; Infection; Medicine; Treatment; Viral disease; Nucleoside analog; Digestive diseases; Antiviral; Genetics; Viral hepatitis C
• ISSN: 0027-9684; 1943-4693
• DOI: 10.1016/S0027-9684(15)31542-X

ABSTRACT We investigated the relationship between global gene expression in peripheral blood mononuclear cells (PBMCs) during the first 4 weeks of peginterferon alfa and ribavirin therapy and long-term eradication of hepatitis-C genotype 1 infections in 23 patients. A sustained virologic response (SVR), defined as an undetected serum HCV ribonucleic acid (RNA) at week 72, was the virologic response endpoint. PBMC RNA was prepared at week 0 and week 4 from 23 patients (17 black and 6 white Americans), and hybridized to Affymetrix GeneChip HG-U133 plus 2.0 arrays. Compared to week 0, 269 genes were differentially expressed at week 4 of treatment, including many genes regulated by alpha interferons and associated with host immunity (p<0.0001), cell signal transduction (p<0.001) and cellular protein metabolism (p<0.001). Expression of these 269 genes at week 0 and week 4 did not differ significantly between patients with and without a SVR. In contrast, SVR was associated with differential expression of 98 genes at week 4 (false discovery rate < 0.01). Many of the genes have been implicated in control of HCV lifecycle and thus may play important roles in HCV clearance during peginterferon and ribavirin therapy.