TY  - BOOK
AU  - Gara, Naveen
TI  - Effect of ribavirin on viral kinetics and liver gene expression in chronic hepatitis C
SN  - 0017-5749
KW  - *Antiviral Agents/pd [Pharmacology]
KW  - *Hepatitis C, Chronic/dt [Drug Therapy]
KW  - *Interferon-alpha/pd [Pharmacology]
KW  - *Liver/de [Drug Effects]
KW  - *Polyethylene Glycols/pd [Pharmacology]
KW  - *Ribavirin/pd [Pharmacology]
KW  - *Transcriptome/de [Drug Effects]
KW  - *Viral Load/de [Drug Effects]
KW  - Adult
KW  - Antiviral Agents/tu [Therapeutic Use]
KW  - Biological Markers/me [Metabolism]
KW  - Drug Administration Schedule
KW  - Drug Therapy, Combination
KW  - Female
KW  - Gene Expression Profiling
KW  - Hepatitis C, Chronic/ge [Genetics]
KW  - Hepatitis C, Chronic/vi [Virology]
KW  - Humans
KW  - Interferon Regulatory Factors/ge [Genetics]
KW  - Interferon Regulatory Factors/me [Metabolism]
KW  - Interferon-alpha/tu [Therapeutic Use]
KW  - Liver/me [Metabolism]
KW  - Liver/vi [Virology]
KW  - Male
KW  - Middle Aged
KW  - Oligonucleotide Array Sequence Analysis
KW  - Polyethylene Glycols/tu [Therapeutic Use]
KW  - Prospective Studies
KW  - Recombinant Proteins/pd [Pharmacology]
KW  - Recombinant Proteins/tu [Therapeutic Use]
KW  - Ribavirin/tu [Therapeutic Use]
KW  - Treatment Outcome
KW  - MedStar Washington Hospital Center
KW  - Medicine/Gastroenterology
KW  - Journal Article
KW  - Randomized Controlled Trial
KW  - Research Support, N.I.H., Intramural
KW  - Research Support, Non-U.S. Gov't
N1  - Available online from MWHC library: 1960 - present, Available in print through MWHC library: 1999 - February 2004
N2  - CONCLUSIONS: Ribavirin is a weak antiviral but its clinical effect seems to be mediated by a separate, indirect mechanism, which may act to reset IFN-responsiveness in HCV-infected liver; DESIGN: 70 treatment-naive patients were randomised to 4 weeks of ribavirin (1000-1200 mg/d) or none, followed by PEG-IFNalpha-2a and ribavirin at standard doses and durations. Patients were also randomised to a liver biopsy 24 h before or 6 h after starting PEG-IFN. Hepatic gene expression was assessed by microarray and interferon-stimulated gene (ISG) expression quantified by nCounter platform. Temporal changes in ISG expression were assessed by qPCR in peripheral-blood mononuclear cells (PBMC) and by serum levels of IP-10; OBJECTIVE: Ribavirin improves treatment response to pegylated-interferon (PEG-IFN) in chronic hepatitis C but the mechanism remains controversial. We studied correlates of response and mechanism of action of ribavirin in treatment of hepatitis C; RESULTS: After 4 weeks of ribavirin monotherapy, hepatitis C virus (HCV) levels decreased by 0.5+0.5 log10 (p=0.009 vs controls) and ALT by 33% (p<0.001). Ribavirin pretreatment, while modestly augmenting ISG induction by PEG-IFN, did not modify the virological response to subsequent PEG-IFN and ribavirin treatment. However, biochemical, but not virological, response to ribavirin monotherapy predicted response to subsequent combination treatment (rapid virological response, 71% in biochemical responders vs 22% non-responders, p=0.01; early virological response, 100% vs 68%, p=0.03; sustained virological response 83% vs 41%, p=0.053). Ribavirin monotherapy lowered serum IP-10 levels but had no effect on ISG expression in PBMC
UR  - http://dx.doi.org/10.1136/gutjnl-2012-303852
ER  -