Do you want to learn something about ribavirin?

[mikesimon]

This is a rather detailed and complicated article about ribavirin and its role in HCV treatment. It's a Medscape article so you must be registered to view. Registration is easy and free and worth the effort.
I will paste the beginning paragraph of the article so you'll have an idea of what you're getting into.

Ribavirin Mode of Action in Chronic Hepatitis C: From Clinical Use Back to Molecular Mechanisms
Posted 12/08/2008

"Ribavirin is an old broad-spectrum antiviral that is highly effective when used in combination with interferon-α and also as part of triple therapies containing new inhibitors of the hepatitis C virus (HCV) non-structural (NS)3/4 protease or HCV NS5B polymerase for the treatment of patients with chronic hepatitis C. However, the molecular mechanisms by which ribavirin enhances early and sustained virological response rates during interferon-based antiviral HCV therapy are still unknown. Several mechanisms including (i) immunomodulatory properties, (ii) inhibition of the inosine monophosphate dehydrogenase, (iii) direct inhibition of the HCV-encoded NS5B RNA polymerase, (iv) induction of lethal mutagenesis and (v) modulation of interferon-stimulated gene expression are currently proposed. Here, we discuss recent advances from in vitro data and their importance for the situation in patients with chronic hepatitis C. Furthermore, theoretical aspects from mathematical modelling of ribavirin action in chronic hepatitis C are reviewed......."

See:  http://www.medscape.com/viewarticle/584208_1


Mike

[geterdone]

So, pre treating with ribavirin prior to the induction of peg interferon heightens the gene expression of the virions so that when the interferon is introduced the now pumped up killer T’s see the genetic error of the virions as a threat and cleaves it where the altered expression is lit? Ok, laymen’s terms here, in the jungle at night ten thousands eyes light up when scanning with a flash light then the (interferon) Killer T’s sees the altered gene expressions of the virions and then the killing begins?  

jasper

interesting read

[jmjm530]

Thanks for posting. An interesting recap as to mechanism.

One mentioned/cited study that caught my eye seems to shed more light on how pre-dosing ribavirin might foster more SVR's. We've talked about pre-dosing riba here for some time and Dr. Dieterich in our professional forum seems to be a proponent as well. Anyway to the study referenced by the Medscape article.

Hepatic gene expression during treatment with peginterferon and ribavirin: Identifying molecular pathways for treatment response.
Feld JJ, Nanda S, Huang Y, Chen W, Cam M, Pusek SN, Schweigler LM, Theodore D, Zacks SL, Liang TJ, Fried MW.

Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.

The reasons for hepatitis C treatment failure remain unknown but may be related to different host responses to therapy. In this study, we compared hepatic gene expression in patients prior to and during peginterferon and ribavirin therapy. In the on-treatment group, patients received either ribavirin for 72 hours prior to peginterferon alpha-2a injection or peginterferon alpha-2a for 24 hours, prior to biopsy. The patients were grouped into rapid responders (RRs) with a greater than 2-log drop and slow responders (SRs) with a less than 2-log drop in hepatitis C virus RNA by week 4. Pretreatment biopsy specimens were obtained from a matched control group. The pretreatment patients were grouped as RRs or SRs on the basis of the subsequent treatment response. Gene expression profiling was performed with Affymetrix microarray technology. Known interferon-stimulated genes (ISGs) were induced in treated patients. In the pretreatment group, future SRs had higher pretreatment ISG expression than RRs. On treatment, RRs and SRs had similar absolute ISG expression, but when it was corrected for the baseline expression with the pretreatment group, RRs showed a greater fold change in ISGs, whereas SRs showed a greater change in interferon (IFN)-inhibitory pathways. The patients pretreated with ribavirin had heightened induction of IFN-related genes and down-regulation of genes involved in IFN inhibition and hepatic stellate cell activation. CONCLUSION: These data suggest that ISG inducibility is important for the treatment response and that ribavirin may improve outcomes by enhancing hepatic gene responses to peginterferon. Collectively, these mechanisms may provide a molecular basis for the improved efficacy of combination therapy.

http://www.ncbi.nlm.nih.gov/pubmed/17929300

[merryBe]

lethal mutagenesis....yup I feel you on that one!!!!

[mikesimon]

I agree for the most part. Usually I see articles advancing one theory or another whereas this article gave equal space to all theories. And, as you said, it does sum it up nicely.
Mike

[Deb_c430]

wow i missed this! Very informative as always, but I with Deb my my sis!  You will have to explain this to me after!     You rock Michael!  as always!

[dointime]

Hi, thanks for posting.  So far as I can make out there's nothing new in this article, although it does sum up the extent of the knowledge there currently is on how riba might work.  

dointime  

[Marcia2202]

Thanks for posting this. It seems to be a very interesting read. Will get onto it when feeling a bit better.

Marcia

[mikesimon]

It is complicated but very informative - it does take some time but I think it's worth the effort.
Mike

[nygirl7]

I think I need to take out a dictionary......you know me.......... ;)

[jdwithhcv]

Thanks Mike