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.  

[comeagain]

On my first tx my weight was 90kg (200lbs) and stayed that way allthrough tx 24weeks.
This tx started up with 89kg after 3 months 80kg current weigt 1month left 78kg.

first tx I was a popcornoholic with a lot of seasalt on also a chocolate and candyholic eated that everyday and relapsed.

This tx time I continued the pocorn habbit first two motnhs but then stopped that candy I only eat once or twice a week.

As I have said here on forum several times before every geno 3 I know of  5-6 persons all got SVR except me and they were all at least 25lbs lighter then me according to their lengt compared with mine.
My gut told me this was important even before I ever heard of IR .

I had had plans to loos weigt before starting this tx but since I had only 10months time and my ex, mother to my children still was txing and I had to take care of children dog and other things I neither had the energi or the time to get in shape.

I´m very glad cowriter is going on about this and even glader cocksparrow is gonna intensify hes engagement if she stops.
My gut is talking even lauder know that this is even more imported then I first thought and more  people can get to SVR and who knows by being forced to change lifestile which is very difficult the older one gets, a curse can be transformed to a blessing.

ca

Ps can´t provide any studys about SVR nr predicted by talking guts.

[bajawoman]

After Jim posted the links from the last Symposium in SF this month I copied many of them for my Doctor this was one on Insulin Resistant as Co Writer mentioned to me it may be an issue with me which is just the info She has given me

AASLD 2008 Annual Meeting

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ID# LB6
Location: General Session Room (Moscone West Convention Center)
Time of Presentation: Nov 03 4:15 PM - 4:30 PM
Category: Q05. HCV: Clinical Trials and Therapeutic Developments



Metformin with Peginterferon Alfa-2a and Ribavirin in the Treatment of Naïve Genotype 1 Chronic Hepatitis C Patients with Insulin Resistance (TRIC-1): Final Results of a Randomized and Double-Blinded Trial.
M. Romero-Gomez1; M. Diago2; R. J. Andrade3; J. Calleja4; J. Salmeron5; C. M. Fernández-Rodriguez6; R. Solà7; J. M. Herrerías8; I. Carmona8; J. García-Samaniego9; R. Moreno-Otero10; R. Morillas11; C. Ramírez13; M. De la Mata12; P. Giner14; A. Olveira15; O. Nuñez16; F. Jorquera17; S. Duran19; R. Martin-Vivaldi18
1. UCM Digestive Diseases, Hospital Universitario de Valme, Sevilla, Spain.
2. Hepatology Section, Hospital General de Valencia , Valencia, Spain.
3. Hepatology Unit, Hospital Universitario Virgen de la Victoria, Málaga, Spain.
4. Gastroenterology Unit, Hospital Puerta de Hierro, Madrid, Spain.
5. UC Aparato Digestivo, Hospital San Cecilio, Granada, Spain.
6. Gastroenterology Unit, Hospital Fundación Alcorcón, Madrid, Spain.
7. Hepatology Section, Hospital del Mar, Barcelona, Spain.
8. Gastroenterology Unit, Hospital Virgen Macarena, Sevilla, Spain.
9. Hepatology Unit, Hospital Carlos III, Madrid, Spain.
10. Digestive Unit, Hospital La Princesa, Madrid, Spain.
11. Digestive Unit, Hospital Germans Trias i Pujol, Badalona, Spain.
12. Hepatology Unit, Hospital Reina Sofia, Córdoba, Spain.
13. Medical Departament, Roche Farma, S.A., Madrid, Spain.
14. Pharmacy Unit, Hospital Germans Trias i Pujol, Badalona, Spain.
15. Digestive Unit, Hospital La Paz, Madrid, Spain.
16. Hepatology Section, Hospital Gregorio Marañón, Madrid, Spain.
17. Digestive Unit, Hospital de León, Leon, Spain.
18. Digestive Service, Hospital Virgen de las Nieves, Granada, Spain.
19. Endocrine Unit, Hospital Universitario de Valme, Sevilla, Spain.

Background&Aims: Insulin resistance affects sustained virological response (SVR) in patients with chronic hepatitis C (CHC). We sought to determine if the addition of metformin to the standard of care regimen could improve SVR in naïve patients with genotype 1 CHC and insulin resistance.
Methods: In a prospective, multicenter, randomized, double-blinded, placebo-controlled trial (TRIC-1), 125 consecutive patients with genotype 1 CHC and insulin resistance (HOMA > 2) received either metformin 425 mg t.id during the first month and 850 mg t.i.d. from week 4 to 48 (Arm A; n=59) or placebo (Arm B; n=64) in addition to peginterferon alfa-2a 180 micrograms weekly and ribavirin 1000-1200 mg daily. Treatment was withdrawal in patients without early virological response (EVR) or HCV-RNA positive at week 24. No baseline differences between arms A and B were seen in the following demographic, biochemical and virological data: age (47+/-8 vs. 48+/-8 years); HOMA (4.3+/-2.2 vs. 4.4+/-2.6); Sydney index (0.43+/-0.27 vs. 0.45+/-0.31); baseline viral load (6.33+/-0.73 vs. 6.48+/-0.76 log10 UI/ml); p=ns for all comparisons. Virological response was assessed at week 4, 12, 24 and 72 by intention-to-treat (ITT) analysis.
Results: In the ITT analysis viral clearance was seen in 54.2% vs. 48.4% at week 12, in 74.6% vs. 75% at week 24, and in 52.5% vs. 42.2% at week 72 (SVR rate) in arm A and arm B respectively. In females (n=54), viral clearance was higher in the metformin arm at week 12 (57.7% vs. 39.3%) at week 24 (80.8% vs. 71.4%) and SVR (57.7% vs. 28.6%;p=0.031). In patients receiving metformin (arm A) viral load decreased during the first 12 weeks in a gender-dependent manner (-4.18+/-1.18 vs. -4.02+/-1.68 log10 IU/ml;p=0.044). SVR was 56.3% in women showing a weight higher than 75 Kg. Patients in arm A showed a greater decrease in their HOMA index than those in arm B (-1.6+/-2.14 vs. -0.87+/-2.11; p=0.008). Triple therapy was well tolerated. Gastrointestinal discomfort, mainly mild diarrhea, was more often seen in arm A (34.1% vs. 11.4%; p<0.05).
Conclusions: Triple therapy with metformin, peginterferon and ribavirin was well tolerated, decreased insulin resistance and increased SVR in this difficult-to-treat group of patients. This therapy was especially effective in females in whom metformin raised significantly the SVR rate. It agrees to the improved sensitivity to metformin reported in obese women. Our data suggest that triple therapy should be the standard of care for females with hepatitis C genotype 1 and insulin resistance.

Acknowledgments: Supported by an unrestricted grant from Roche-Farma, S.A.

[epiphiny]

Wow!  That's an impressive weight loss.  

I went the other way on my first tx from 62kg to 72kg (I'm 6'00 so that made me pretty skinny at 62kgs) and despite being skinny had no viral response.

I never lost the additional weight, in fact gained another 5kgs, before I started this tx which makes me a little overweight and this time I'm responding to tx.

I still smoke BUT last time round I was smoking about 25 - 30 a day and this time I smoke between 2 and 8 and I never smoke a full cigarette.

There are so many variables with this virus, I just don't see how we can really predict any outcomes but I think in a strange way it helps us to try.  As humans we are always trying to find patterns and reasons, some kind of order in the chaos.

Sometimes it drives me mad trying to figure it all out but I have developed a taste for Madon Sea Salt and have been dipping my fingertips in it and licking them, so I'll keep on with that!  Incidentally, I was a chocoholic before tx as well.....

Epi.

[bajawoman]

Hey there  very interesting post to me   especially the weight loss and clothing sizes After TX WOW  that is wonderful news you must feel like a new woman and have fun wearing clothes

well what do you attribute losing weight too?

Doesn't sound like you dieted? I didn't hear anything about excercise either after tx and during tx you even gained weight??  And if I am reading it right you went off tx then lost wieght

And is seems you were taken off tx early but yet managed SVR this is great news

And you also said you were IR at the beginning of Tx  so you are one of the exceptions all the way around to the reactions and actions around tx

Another thing is you are saying your liver is healing itself  so your viral load is low what was the grade and stage and your viral load?  when you began tx? you were also IR ? You really are one of the lucky ones  
Not sure how many here smoke that may be a factor in my case with high Viral Load and IR but I am changing my diet and starting to excercise and will quit smoking I am a lot older than you so maybe weaker to the sx of tx and SVR

[meki]

Oh - and Stranger still - with my diet (containing salt products instead of sweets all the time) --- I've dropped 60+ pounds...

And about 10 clothing sizes.

I went from 205 prior to TX --- up to 215 during TX until the end of TX.

And now almost a year and 8 months Post TX I'm down to 145 pounds...

From a size 22 women's plus to a 12 avg.

[meki]

Now - explain this:

Mild to moderate Steatosis and IR --- Gained weight on TX --- I did not RVR, in fact LATE response... If there is a word for that... 18th week finally decreased. Did not extend TX - and managed SVR.

Also Moderate Damage to liver now at grade 1 stage 2... (GOING DOWN FOLKS --- so this DOES mean that the LIVER does INDEED heal itself --- and fairly rapidly too...)

So --- You're saying that my instance is unusual based on the fact that I probaly have all three of those jeans.... Oooops... I mean genes.... LOL!

Anyhow -- that's a lot of mouthful there.

I think that it's probable --- that a lot of things can affect --- and effect --- the probability of SVR status....

Like a CodeBreaker - a thief - HCV insinuates itself inside cellular structures and replicates, taking advantage of different elements...

So it thrives in environments that those specific genes produce.

It makes sense...

I'm just more and more amazed that I actually obtained SVR status --- and I'm counting my lucky stars... and feel so very blessed - as I watch more and more folks struggle with the NON RESPONDER status...

Which may very well encompass having these genes --- and other factors which cause them.

So - I'm thinking --- people who seriously want to reach UND - must lose weight, take weight based Riba - eat less fatty foods, maintain non-sugary content eating ---- must exercise to keep everything moving --- and must adapt to a very healthy lifestyle...

For those who are IR --- they must follow through even more so ---- correct?

Now --- let me ask this:

It's going to sound like an extremely STRANGE question.

WOULD HIGH SODIUM INTAKE AFFECT ANYTHING?

Because --- at the middle of my TX --- I started craving --- Unbelievably a HIGH SODIUM diet... I ate everything Salty --- couldn't stand sweet stuff --- except yogurt (vanilla or peach only) --- fresh Canteloupe and popsicles... (occassional binges on Oreos don't count - LOL!)

But at the middle to NOW currently - I've moved from Chocoholic status to SALT FREAK.

Could that have ANY bearing at all on IR or SVR status?

Don't laugh - I'm asking seriously.

The reason I'm asking is because right around when I started eating Salt --- is when I started responding to the medications... And I never thought anything about it...

I know that probiotics are important --- so maybe salt is too?

I mean  - I ate a yogurt a day ---- and at least a half a bag of potato chips (healthier ones, of course --- or when unavailable - I stuffed my face with kettle ones... LOL!)

But seriously --- could sodium or salt content have any bearing on any of this?

I know sugar does -- adversely...

OK - I'm shutting up now... You guys can go ahead and laugh... LOL!

I'll love all of you anyway.

Hugs,

Meki