Effect of ribavirin on viral kinetics and liver gene expression in chronic hepatitis C.
Citation: Gut. 63(1):161-9, 2014 Jan.PMID: 23396509Institution: MedStar Washington Hospital CenterDepartment: Medicine/GastroenterologyForm of publication: Journal ArticleMedline article type(s): Journal Article | Randomized Controlled Trial | Research Support, N.I.H., Intramural | Research Support, Non-U.S. Gov'tSubject headings: *Antiviral Agents/pd [Pharmacology] | *Hepatitis C, Chronic/dt [Drug Therapy] | *Interferon-alpha/pd [Pharmacology] | *Liver/de [Drug Effects] | *Polyethylene Glycols/pd [Pharmacology] | *Ribavirin/pd [Pharmacology] | *Transcriptome/de [Drug Effects] | *Viral Load/de [Drug Effects] | Adult | Antiviral Agents/tu [Therapeutic Use] | Biological Markers/me [Metabolism] | Drug Administration Schedule | Drug Therapy, Combination | Female | Gene Expression Profiling | Hepatitis C, Chronic/ge [Genetics] | Hepatitis C, Chronic/vi [Virology] | Humans | Interferon Regulatory Factors/ge [Genetics] | Interferon Regulatory Factors/me [Metabolism] | Interferon-alpha/tu [Therapeutic Use] | Liver/me [Metabolism] | Liver/vi [Virology] | Male | Middle Aged | Oligonucleotide Array Sequence Analysis | Polyethylene Glycols/tu [Therapeutic Use] | Prospective Studies | Recombinant Proteins/pd [Pharmacology] | Recombinant Proteins/tu [Therapeutic Use] | Ribavirin/tu [Therapeutic Use] | Treatment OutcomeLocal holdings: Available online from MWHC library: 1960 - present, Available in print through MWHC library: 1999 - February 2004ISSN:- 0017-5749
Item type | Current library | Collection | Call number | Status | Date due | Barcode |
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Journal Article | MedStar Authors Catalog | Article | Available | 23396509 |
Available online from MWHC library: 1960 - present, Available in print through MWHC library: 1999 - February 2004
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.
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