SOCS3 Gene: Insulin Resistance, IFN resistance

[MKAndrew]

For six years, I believed there was a single-source connection between interferon resistance and interferon resistance.  It is, as I suspected, a gene.  The gene is SOCS3 - Suppressor Of Cytokine Signaling-3.  The discovery of this gene also sheds some light on why prior nonresponders have more trouble acheiving SVR.

1. SOCS-3 is elevated by HCV's core protein.

2. SOCS-3 elevation causes interferon resistance.

3. SOCS-3 elevation causes insulin resistance in the liver.

4. SOCS-3 depletion reduces liver insulin resistance, but causes systemic insulin resistance.

5. SOCS-3 is further elevated in people who have treated unsuccessfully.

These findings suggest a new and viable target for therapy.  

[CockSparrow]

Thanks.
I hope they do a better job than this study did. Talk about mess it up.
Pioglitazone (Actos) in chronic hepatitis C not responding to pegylated interferon-a and ribavirin Journal of Hepatology 49 (2008) 295–298

Background/Aims:
Insulin resistance reduces the response to interferon alfa-based therapy of chronic hepatitis C patients. It has been speculated that improvement of insulin sensitivity might increase the chances of responding to treatment of such individuals.

Methods:
We started a multicenter clinical trial of retreatment of chronic hepatitis C patients, who had failed to respond to the pegylated interferon alfa/ribavirin combination, with a triple therapy consisting in these same antivirals plus an insulin-sensitizer (pioglitazone) (The INSPIRED-HCV study).

Results:
None of the first five patients fulfilling the inclusion criteria and included in the trial had a satisfactory virological response after 12 weeks of retreatment, despite the fact that in at least three of them the insulin resistance score improved. As a result, the study was terminated.

Conclusions:
Different schedules are warranted to improve insulin sensitivity prior to attempting retreatment of chronic hepatitis C patients with insulin resistance.

CS

[Proactive]

Think I might have mentioned it this Spring, but my doc made a comment of his involvement with an upcoming Hep C/insulin resistance trial..Might be old news to you, but stumbled on a tiny bit of info, seems it started this Summer..
http://www.dhmc.org/webpage.cfm?site_id=2&org_id=102&morg_id=0&sec_id=0&gsec_id=46442&item_id=46494

[CockSparrow]

Interesting 1st post.
If by dont push it you mean dont push the Insulin Resistance thing
Then If Co dont push It I will.

Whats your game.
CS

[CoWriter]

"Did I understand correctly that "SVR for Females 57.7% vs 28.6% " was achieved in SOC and Metaformin compared to those females with SOC and placebo?"


That's right.  The women did much better than the men.  

And the SVR  of 52.5%  vs  42.2%  is for ITT.  

They started with 123 patients and 22 of them discontinued because of non-compliance, they chose to stop before week 24, lost to follow-up, etc.

Of the 101 that finished the study, SVR was 67.4% vs 49.1%

(and people may do better if the Metformin is started before tx)



"This is really astonishing stuff and you'd think it would make giant waves. If I were a female with insulin-resistance, I'd pay close, close attention. "


The bad thing is that most doctors don't test patients for insulin resistance.

The info on insulin resistance has been out there for years and docs have done nothing about it.  They kept saying that there was data that proved that insulin resistance lowered SVR but there was no data that proved that improving insulin resistance would increase SVR....

Which drove me absolutely crazy!

Well....there's data now.  Let's see what they'll do with it.

Co

[portann]

Co: "SOC+Metformin vs SOC+placebo

      SVR  52.5%  vs  42.2%
      HOMA-IR less than 2 at Week 24  55% vs 13.6%
      SVR for Females 57.7% vs 28.6%"

----------------------------------------------------------------------------------
Did I understand correctly that "SVR for Females 57.7% vs 28.6% " was achieved in SOC and Metaformin compared to those females with SOC and placebo?

I haven't been following the forum much but presumably this relates to females who are insulin-resistant before treatment? This is really astonishing stuff and you'd think it would make giant waves. If I were a female with insulin-resistance, I'd pay close, close attention.

[CoWriter]

These are the final reasults of the Metformin+SOC study....(genotype 1, they all had a HOMA greater than 2 and the study used Metformin 425mg tid for 4 weeks, then increased it to 850mg tid).


"Adding Metformin to Standard Peginterferon alfa-2a/Ribavirin Regimen Improves Insulin Sensitivity in Patients With HCV Infection

SOC+Metformin vs SOC+placebo

SVR  52.5%  vs  42.2%
HOMA-IR less than 2 at Week 24  55% vs 13.6%
SVR for Females 57.7% vs 28.6%


Summary of Key Conclusions:

Metformin added to peginterferon alfa-2a/ribavirin regimen in genotype 1 HCV-infected patients with insulin resistance....
    * Significantly improves insulin sensitivity.
    * Shows trend toward improved sustained virologic response (SVR) rates.
    *  Ad hoc analysis found significant improvement in SVR rates for female patients only.
Treating insulin resistance potential new goal for HCV therapy."



Now they need to stop messing around and quit using suboptimal doses ...and start the Metformin earlier.

Co