Early gene expression profiles of patients with chronic hepatitis C treated with pegylated interferon-alfa and ribavirin.
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-alpha2a) or PEG-IFN-alpha2b 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.


CONCLUSIONS
Early gene expression during anti-HCV therapy may elucidate important molecular pathways that may be influencing the probability of achieving virologic response.
Younossi
Zobair M
ZM
Center for Liver Diseases at Inova Fairfax Hospital, Falls Church, VA 22042, USA. zobair.younossi@inova.org
Baranova
Ancha
A
Afendy
Arian
A
Collantes
Rochelle
R
Stepanova
Maria
M
Manyam
Ganiraju
G
Bakshi
Anita
A
Sigua
Christopher L
CL
Chan
Joanne P
JP
Iverson
Ayuko A
AA
Santini
Christopher D
CD
Chang
Sheng-Yung P
SY
D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D054405:Chemokine CCL3 / Q000235:genetics / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D020869:Gene Expression Profiling; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D050836:Interferon Regulatory Factor-2 / Q000235:genetics / Q000378:metabolism; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D008957:Models, Genetic; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use*; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D000998:Antiviral Agents; D054405:Chemokine CCL3; C494229:IRF2 protein, human; D050836:Interferon Regulatory Factor-2; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D025521:Tumor Suppressor Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a