Re: Therapies to Manage Insulin Resistance Improve Response to Interferon-based Ther

[Guest guest]

Now days the odds are higher so don't give up on treating just yet . With the addition of protease inhibitors comes a higher % of SVR .My tail bone (broken is hurtin real bad tonight) so sleep may not be forthcoming . Besides when I feel up this much its hard to pass up on a chance to catch up on the research material ,lol nite hun sleep well.

Therapies to Manage Insulin Resistance Improve Response to Interferon-based TherTo: Hepatitis_C_Central Date: Saturday, November 29, 2008, 4:04 AM

Therapies to Manage Insulin Resistance Improve Response to Interferon-based Therapy in Chronic Hepatitis C Patients By Liz Highleyman

Several prior studies have shown that people with chronic hepatitis C virus (HCV) infection are more likely to have insulin resistance or diabetes, and that these conditions in turn are associated with poorer response to interferon-based therapy. This observation has led experts to suggest that managing insulin resistance might improve hepatitis C treatment outcomes.

MetforminIn a late-breaker presentation at the recent 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2008), Spanish investigators described findings from the TRIC-1 trial, which assessed whether adding the insulin-sensitizing drug metformin (Glucopahge) to pegylated interferon plus ribavirin could improve sustained virological response (SVR) rates in individuals with insulin resistance.

This prospective, multicenter, double-blind trial included 125 genotype 1 chronic hepatitis C patients with baseline insulin resistance (HOMA-IR score > 2) who were randomly assigned to receive either metformin (425 thrice-daily for the first month, then 850 mg thrice-daily from week 4 to 48) or placebo, in combination with 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus 1000-1200 mg/day weight-adjusted ribavirin for 48 weeks. Participants who did not achieve early virological response (EVR) at week 12 or who still had detectable HCV RNA at week 24 discontinued treatment early.

Baseline characteristics were similar in the 2 arms, including demographic factors, HOMA-IR scores (about 4.4), and baseline HCV RNA (about 6.4 log10 IU/mL). 57% were men and the mean age was about 48 years.

Results

• Patients in the metformin arm experienced a greater decrease in HOMA-IT scores compared with the placebo arm.• In an intent-to-treat analysis, overall rates of virological clearance in the 2 arms were as follows:

• Week 12 (EVR): 54.2% in the metformin arm vs 48.4% in the placebo arm;• Week 24: 74.6% vs 75.0%, respectively;• Week 72 (SVR): 52.5% vs 42.2%, respectively.

• Among the 54 women, however, rates of viral clearance were higher in the metformin arm:

• Week 12: 57.7% in the metformin arm vs 39.3% in the placebo arm;• Week 24: 80.8% vs 71.4%, respectively;• Week 72 (SVR): 57.7% vs 28.6%, respectively.

• Among patients receiving metformin, HCV viral load decreased during the first 12 weeks in a gender-dependent manner. • The beneficial effect of metformin was most pronounced in heavier weight women (> 75 kg, or about 165 lb).• Metformin triple therapy was generally well tolerated, but gastrointestinal symptoms -- mainly mild diarrhea -- were more frequent in the metformin arm.

"Triple therapy with metformin, peginterferon, and ribavirin was well tolerated, decreased insulin resistance and increased SVR in this difficult-to- treat group of patients," the researchers concluded.

"This therapy was especially effective in females, in whom metformin raised significantly the SVR rate," they added. "Our data suggest that triple therapy should be the standard of care for females with hepatitis C genotype 1 and insulin resistance."

Pioglitazone

In a related, but smaller and shorter, study also presented at the conference, another research team reported results from an analysis of early viral decay in non-diabetic genotype 1 hepatitis C patients who added pioglitazone (Actos) to pegylated interferon plus ribavirin. Pioglitazone is a thiazolidinedione anti-diabetes medication from a different drug class than metformin.

In this study, a group of 10 obese patients (body mass index > 30) received 30 mg/day pioglitazone starting 4 weeks prior to interferon-based therapy and continued with 4 weeks of combination therapy (8 total weeks of pioglitazone) . These patients were compared with obese and normal-weight control patients (10 each) who received standard hepatitis C treatment without pioglitazone.

Results

• Addition of pioglitazone improved the viral decay rate during the first 4 weeks of interferon-based therapy. • At days 2, 7, 14, and 28, the average decrease in HCV RNA was smaller among obese patients receiving standard pegylated interferon/ribaviri n compared with the lean participants taking the same regimen (3.8 vs 4.3 log on day 28). • However, obese patients who added pioglitazone had a greater decline at each time point than obese patients on standard therapy (5.3 vs 3.8 log on day 28). • At week 4, 60% of obese patients receiving pioglitazone triple therapy achieved rapid virological response, compared with 50% of normal-weight patients on standard therapy and 20% of obese patients not taking pioglitazone.

Based on these findings, the researchers concluded, "Pioglitazone given [as an] adjuvant to [pegylated interferon/ribaviri n] in HCV genotype 1 patients improves viral kinetic response during the first 4 weeks of therapy."

[Guest guest]

Suzi, its so important to keep your blood sugars stable, especially while on tx.. I was given only 10-15% chance of even responding to tx and NO, ZERO, zippo chance of ever reaching SVR and I DID both... it can be done hon.. and like liz said, with the protease inhibitors, your chances of reaching svr are much better.. I know several 1b's who are SVR 4 plus years now,,

From: <elizabethnv1@ earthlink. net>Subject: [Hepatitis_C_ Central] Therapies to Manage Insulin Resistance Improve Response to Interferon-based TherTo: Hepatitis_C_ Central@yahoogro ups.comDate: Saturday, November 29, 2008, 4:04 AM

Therapies to Manage Insulin Resistance Improve Response to Interferon-based Therapy in Chronic Hepatitis C Patients By Liz Highleyman

Several prior studies have shown that people with chronic hepatitis C virus (HCV) infection are more likely to have insulin resistance or diabetes, and that these conditions in turn are associated with poorer response to interferon-based therapy. This observation has led experts to suggest that managing insulin resistance might improve hepatitis C treatment outcomes.

MetforminIn a late-breaker presentation at the recent 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2008), Spanish investigators described findings from the TRIC-1 trial, which assessed whether adding the insulin-sensitizing drug metformin (Glucopahge) to pegylated interferon plus ribavirin could improve sustained virological response (SVR) rates in individuals with insulin resistance.

This prospective, multicenter, double-blind trial included 125 genotype 1 chronic hepatitis C patients with baseline insulin resistance (HOMA-IR score > 2) who were randomly assigned to receive either metformin (425 thrice-daily for the first month, then 850 mg thrice-daily from week 4 to 48) or placebo, in combination with 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus 1000-1200 mg/day weight-adjusted ribavirin for 48 weeks. Participants who did not achieve early virological response (EVR) at week 12 or who still had detectable HCV RNA at week 24 discontinued treatment early.

Baseline characteristics were similar in the 2 arms, including demographic factors, HOMA-IR scores (about 4.4), and baseline HCV RNA (about 6.4 log10 IU/mL). 57% were men and the mean age was about 48 years.

Results

• Patients in the metformin arm experienced a greater decrease in HOMA-IT scores compared with the placebo arm.• In an intent-to-treat analysis, overall rates of virological clearance in the 2 arms were as follows:

• Week 12 (EVR): 54.2% in the metformin arm vs 48.4% in the placebo arm;• Week 24: 74.6% vs 75.0%, respectively;• Week 72 (SVR): 52.5% vs 42.2%, respectively.

• Among the 54 women, however, rates of viral clearance were higher in the metformin arm:

• Week 12: 57.7% in the metformin arm vs 39.3% in the placebo arm;• Week 24: 80.8% vs 71.4%, respectively;• Week 72 (SVR): 57.7% vs 28.6%, respectively.

• Among patients receiving metformin, HCV viral load decreased during the first 12 weeks in a gender-dependent manner. • The beneficial effect of metformin was most pronounced in heavier weight women (> 75 kg, or about 165 lb).• Metformin triple therapy was generally well tolerated, but gastrointestinal symptoms -- mainly mild diarrhea -- were more frequent in the metformin arm.

"Triple therapy with metformin, peginterferon, and ribavirin was well tolerated, decreased insulin resistance and increased SVR in this difficult-to- treat group of patients," the researchers concluded.

"This therapy was especially effective in females, in whom metformin raised significantly the SVR rate," they added. "Our data suggest that triple therapy should be the standard of care for females with hepatitis C genotype 1 and insulin resistance."

Pioglitazone

In a related, but smaller and shorter, study also presented at the conference, another research team reported results from an analysis of early viral decay in non-diabetic genotype 1 hepatitis C patients who added pioglitazone (Actos) to pegylated interferon plus ribavirin. Pioglitazone is a thiazolidinedione anti-diabetes medication from a different drug class than metformin.

In this study, a group of 10 obese patients (body mass index > 30) received 30 mg/day pioglitazone starting 4 weeks prior to interferon-based therapy and continued with 4 weeks of combination therapy (8 total weeks of pioglitazone) . These patients were compared with obese and normal-weight control patients (10 each) who received standard hepatitis C treatment without pioglitazone.

Results

• Addition of pioglitazone improved the viral decay rate during the first 4 weeks of interferon-based therapy. • At days 2, 7, 14, and 28, the average decrease in HCV RNA was smaller among obese patients receiving standard pegylated interferon/ribaviri n compared with the lean

participants taking the same regimen (3.8 vs 4.3 log on day 28). • However, obese patients who added pioglitazone had a greater decline at each time point than obese patients on standard therapy (5.3 vs 3.8 log on day 28). • At week 4, 60% of obese patients receiving pioglitazone triple therapy achieved rapid virological

response, compared with 50% of normal-weight patients on standard therapy and 20% of obese patients not taking pioglitazone.

Based on these findings, the researchers concluded, "Pioglitazone given [as an] adjuvant to [pegylated interferon/ribaviri n] in HCV genotype 1 patients improves viral kinetic response during the first 4 weeks of therapy."