TY - JOUR
T1 - Early gene expression profiles of patients with chronic hepatitis C treated with pegylated interferon- Alfa and Ribavirin
AU - Younossi, Zobair M.
AU - Baranova, Ancha
AU - Afendy, Arian
AU - Collantes, Rochelle
AU - Stepanova, Maria
AU - Manyam, Ganiraju
AU - Bakshi, Anita
AU - Sigua, Christopher L.
AU - Chan, Joanne P.
AU - Iverson, Ayuko A.
AU - Santini, Christopher D.
AU - Chang, Sheng Yung P.
PY - 2009
Y1 - 2009
N2 - Responsiveness to hepatitis C virus (HCV) therapy depends on viral and host factors. Our aim was to assess sustained virologic response (SVR)-associated early gene expression in patients with HCV receiving pegylated interferon-alpha2a (PEG-IFN-α2a) or PEG-IFN-α2b and ribavirin with the duration based on genotypes. Blood samples were collected into PAXgene tubes prior to treatment as well as 1, 7, 28, and 56 days after treatment. From the peripheral blood cells, total RNA was extracted, quantified, and used for one-step reverse transcription polymerase chain reaction to profile 154 messenger RNAs. Expression levels of messenger RNAs were normalized with six "housekeeping" genes and a reference RNA. Multiple regression and stepwise selection were performed to assess differences in gene expression at different time points, and predictive performance was evaluated for each model. A total of 68 patients were enrolled in the study and treated with combination therapy. The results of gene expression showed that SVR could be predicted by the gene expression of signal transducer and activator of transcription-6 (STAT-6) and suppressor of cytokine signaling-1 in the pretreatment samples. After 24 hours, SVR was predicted by the expression of interferon-dependent genes, and this dependence continued to be prominent throughout the treatment. Conclusion: Early gene expression during anti-HCV therapy may elucidate important molecular pathways that may be influencing the probability of achieving virologic response.
AB - Responsiveness to hepatitis C virus (HCV) therapy depends on viral and host factors. Our aim was to assess sustained virologic response (SVR)-associated early gene expression in patients with HCV receiving pegylated interferon-alpha2a (PEG-IFN-α2a) or PEG-IFN-α2b and ribavirin with the duration based on genotypes. Blood samples were collected into PAXgene tubes prior to treatment as well as 1, 7, 28, and 56 days after treatment. From the peripheral blood cells, total RNA was extracted, quantified, and used for one-step reverse transcription polymerase chain reaction to profile 154 messenger RNAs. Expression levels of messenger RNAs were normalized with six "housekeeping" genes and a reference RNA. Multiple regression and stepwise selection were performed to assess differences in gene expression at different time points, and predictive performance was evaluated for each model. A total of 68 patients were enrolled in the study and treated with combination therapy. The results of gene expression showed that SVR could be predicted by the gene expression of signal transducer and activator of transcription-6 (STAT-6) and suppressor of cytokine signaling-1 in the pretreatment samples. After 24 hours, SVR was predicted by the expression of interferon-dependent genes, and this dependence continued to be prominent throughout the treatment. Conclusion: Early gene expression during anti-HCV therapy may elucidate important molecular pathways that may be influencing the probability of achieving virologic response.
UR - https://www.scopus.com/pages/publications/63349092061
U2 - 10.1002/hep.22729
DO - 10.1002/hep.22729
M3 - Article
C2 - 19140155
AN - SCOPUS:63349092061
SN - 0270-9139
VL - 49
SP - 763
EP - 774
JO - Hepatology
JF - Hepatology
IS - 3
ER -