Aa
Double dosing for the chubbs
Reading the ClinicCare article on Steatosis found this interesting....
weighing more than 85 kg who were treated with 270 μg of peginterferon alfa-2a were found to have higher serum trough concentrations of the drug and a higher overall SVR rate.[56,57] Further investigation is under way to assess the efficacy of higher fixed doses of peginterferon alfa-2a and ribavirin in obese patients.
Wondering if us chubbs have doctors aware of this...
...Finally, obesity can contribute to fibrosis progression by impairing response to interferon-based therapy. This may occur in part because obesity reduces the bioavailability of interferon. Conventional and peginterferons are injected subcutaneously and preferentially taken up by the lymphatic system. Patients with large amounts of subcutaneous fat may have impaired absorption of the drug because of decreased lymphatic uptake.[55] Although the 2 available types of peginterferon alfa are dosed differently (peginterferon alfa-2a is administered at a fixed dose of 180 μg, whereas peginterferon alfa-2b is dosed at 1.5 μg per kilogram of body weight), the maximum recommended weekly doses are 180 μg of peginterferon alfa-2a and 150 μg of peginterferon alfa-2b. Patients weighing more than 100 kg may therefore receive a suboptimal dose of peginterferon alfa-2b if dosed according to guidelines. Recent data suggest that 180 μg of peginterferon alfa-2a may also be insufficient for heavier patients. In some studies, patients
Info at: http://clinicaloptions.com/Hepatitis/Annual%20Updates/2007%20Annual%20Update/Modules/Harrison/Pages/Page%208.aspx
weighing more than 85 kg who were treated with 270 μg of peginterferon alfa-2a were found to have higher serum trough concentrations of the drug and a higher overall SVR rate.[56,57] Further investigation is under way to assess the efficacy of higher fixed doses of peginterferon alfa-2a and ribavirin in obese patients.
Wondering if us chubbs have doctors aware of this...
...Finally, obesity can contribute to fibrosis progression by impairing response to interferon-based therapy. This may occur in part because obesity reduces the bioavailability of interferon. Conventional and peginterferons are injected subcutaneously and preferentially taken up by the lymphatic system. Patients with large amounts of subcutaneous fat may have impaired absorption of the drug because of decreased lymphatic uptake.[55] Although the 2 available types of peginterferon alfa are dosed differently (peginterferon alfa-2a is administered at a fixed dose of 180 μg, whereas peginterferon alfa-2b is dosed at 1.5 μg per kilogram of body weight), the maximum recommended weekly doses are 180 μg of peginterferon alfa-2a and 150 μg of peginterferon alfa-2b. Patients weighing more than 100 kg may therefore receive a suboptimal dose of peginterferon alfa-2b if dosed according to guidelines. Recent data suggest that 180 μg of peginterferon alfa-2a may also be insufficient for heavier patients. In some studies, patients
Info at: http://clinicaloptions.com/Hepatitis/Annual%20Updates/2007%20Annual%20Update/Modules/Harrison/Pages/Page%208.aspx
I don't trust chains anyway (Ruths Chris might be an exception) so I think that is a wise move. Mike
1) I assume a free diet is one with no restrictions.
2) A diet which restricts carbohydrate intake would help to reduce glucose levels - fasting and post prandial.
3) I don't recall anything that suggests not using medication to improve insulin resistance/glucose profile.
4) I don't eat at OutBack but I assume you could find foods on their menu that would not be counterproductive. Portion control, vegetables (not potatoes or corn in excess), no or very small bread intake (or other starches) and no sweet desert might be a good start. A diabetic diet is a healthy diet for almost everyone.
Mike
Mike
2) A diet which restricts carbohydrate intake would help to reduce glucose levels - fasting and post prandial.
3) I don't recall anything that suggests not using medication to improve insulin resistance/glucose profile.
4) I don't eat at OutBack but I assume you could find foods on their menu that would not be counterproductive. Portion control, vegetables (not potatoes or corn in excess), no or very small bread intake (or other starches) and no sweet desert might be a good start. A diabetic diet is a healthy diet for almost everyone.
Mike
Mike
Read the full text. (heady stuff) i am a bit confused so maybe someone can help me out.
...Tarantino et al. [23] have recently reported that patients with metabolic syndrome and chronic hepatitis C (N = 15) presented a response rate of 60% with combined therapy after 3 months of strict diet accompanied by weight and insulin resistance reduction compared to a 17.5% response rate in a similar group of patients (N = 17) on a free diet....
1st: What is a free diet?
2nd: What type of diet or foods help normalize glucose?
3rd; This report doesn't seem to dispute using insulin resitance drugs.
4th: Guess I am not going OutBacking tonight!
...Tarantino et al. [23] have recently reported that patients with metabolic syndrome and chronic hepatitis C (N = 15) presented a response rate of 60% with combined therapy after 3 months of strict diet accompanied by weight and insulin resistance reduction compared to a 17.5% response rate in a similar group of patients (N = 17) on a free diet....
1st: What is a free diet?
2nd: What type of diet or foods help normalize glucose?
3rd; This report doesn't seem to dispute using insulin resitance drugs.
4th: Guess I am not going OutBacking tonight!
I can't in good conscience "weigh" in on the advisability of hitting OutBack - pardon the pun. I advise you to read the entire article because it does have a slightly different perspective on this issue and one which may be of interest to you. Mike
Therefore, it is likely that glucose abnormality rather than obesity itself was a more important factor accounting for the lower response to treatment observed in patients with obesity.
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Does this mean I can hit the "OutBack" tonight?
-------------------------------------------------------
Does this mean I can hit the "OutBack" tonight?
Glucose Abnormalities Are an Independent Risk Factor for Nonresponse to Antiviral Treatment in Chronic Hepatitis C
http://www.medscape.com/viewarticle/563991_1
"It is consequently understandable that glucose abnormalities, but not the other components associated with insulin resistance, were independently related to SVR. In this regard, although obesity has been proposed as an independent risk factor for nonresponse to antiviral treatment in chronic hepatitis C, no information on glucose metabolism was given in these reports. [12–14] Therefore, it is likely that glucose abnormality rather than obesity itself was a more important factor accounting for the lower response to treatment observed in patients with obesity. In the present study, apart from the presence of glucose abnormalities and HCV genotype 1, high levels of GGT were also independently related to no response to antiviral treatment. Regarding GGT, it should be noted that it has been closely associated with insulin resistance in the setting of both obese and nonobese individuals with hepatic steatosis due to different etiologies including chronic HCV infection. [15–18] It has been proposed that insulin resistance reduces insulin-dependent suppression of lipolysis [19] and the release of very low-density lipoproteins from the liver. [20]
Both conditions are likely to increase triglyceride contents in the hepatocytes, and consequently, hepatic steatosis. Furthermore, several prospective studies have demonstrated that serum GGT is an independent predictor for developing metabolic syndrome and diabetes. [15,21] In addition, recent data indicate an inverse correlation between serum levels of adiponectin, an adipocyte-derived hormone that protects against insulin resistance and type 2 diabetes, and serum GGT values in patients with HCV-related steatosis. [22] Hepatic steatosis may contribute to HCV-associated diabetes by impairing the insulin ability to lower hepatic glucose production and favoring liver fibrosis. [4] In our study, where the mean BMI corresponds to nonobese subjects, GGT correlates with fasting glucose when all patients are evaluated, but only type 2 diabetic patients show higher levels of GGT. Moreover, in a recent study, both steatosis and GGT were predictors of insulin resistance in HCV infected patients, but no correlation existed between GGT and the extent of steatosis, suggesting that other factors beyond steatosis per se are responsible for higher GGT levels in these patients. [23] Alternatively, insulin resistance can adversely affect the course of chronic hepatitis C and lead to enhanced steatosis, steatohepatitis, and liver fibrosis. [4] Therefore, it is not surprising that GGT also appears as an independent risk factor for nonresponse to combined antiviral therapy in our cohort, which has been previously reported by Berg et al. [24]"
Mike
http://www.medscape.com/viewarticle/563991_1
"It is consequently understandable that glucose abnormalities, but not the other components associated with insulin resistance, were independently related to SVR. In this regard, although obesity has been proposed as an independent risk factor for nonresponse to antiviral treatment in chronic hepatitis C, no information on glucose metabolism was given in these reports. [12–14] Therefore, it is likely that glucose abnormality rather than obesity itself was a more important factor accounting for the lower response to treatment observed in patients with obesity. In the present study, apart from the presence of glucose abnormalities and HCV genotype 1, high levels of GGT were also independently related to no response to antiviral treatment. Regarding GGT, it should be noted that it has been closely associated with insulin resistance in the setting of both obese and nonobese individuals with hepatic steatosis due to different etiologies including chronic HCV infection. [15–18] It has been proposed that insulin resistance reduces insulin-dependent suppression of lipolysis [19] and the release of very low-density lipoproteins from the liver. [20]
Both conditions are likely to increase triglyceride contents in the hepatocytes, and consequently, hepatic steatosis. Furthermore, several prospective studies have demonstrated that serum GGT is an independent predictor for developing metabolic syndrome and diabetes. [15,21] In addition, recent data indicate an inverse correlation between serum levels of adiponectin, an adipocyte-derived hormone that protects against insulin resistance and type 2 diabetes, and serum GGT values in patients with HCV-related steatosis. [22] Hepatic steatosis may contribute to HCV-associated diabetes by impairing the insulin ability to lower hepatic glucose production and favoring liver fibrosis. [4] In our study, where the mean BMI corresponds to nonobese subjects, GGT correlates with fasting glucose when all patients are evaluated, but only type 2 diabetic patients show higher levels of GGT. Moreover, in a recent study, both steatosis and GGT were predictors of insulin resistance in HCV infected patients, but no correlation existed between GGT and the extent of steatosis, suggesting that other factors beyond steatosis per se are responsible for higher GGT levels in these patients. [23] Alternatively, insulin resistance can adversely affect the course of chronic hepatitis C and lead to enhanced steatosis, steatohepatitis, and liver fibrosis. [4] Therefore, it is not surprising that GGT also appears as an independent risk factor for nonresponse to combined antiviral therapy in our cohort, which has been previously reported by Berg et al. [24]"
Mike
I think I really pissed her off. I got to learn to stop joking around so much. I have alienated some here I think.
Keep an eye out for 'PSP N Me'. She might be involved in the IR trial and I think she's around week 30 of 48 tx.
from the module....
...Pharmacologic agents that decrease insulin resistance provide another intriguing strategy for reducing steatosis and improving response to hepatitis C treatment. One class of medications, the thiazolidinediones (TZDs), improve insulin sensitivity through activation of the peroxisome proliferator-activated receptor-gamma (PPAR-γ) in adipocytes and skeletal muscle.[68] Pioglitazone, one of 2 currently available PPAR-γ ligands, decreases insulin resistance, lowers TNF-α levels, increases adiponectin levels (thereby, increasing PPAR-α ligand activity), and reduces hepatic steatosis in NASH patients.[69] Further, data suggest that pioglitazone also decreases SOCS-3 expression.[70] Ultimately, if increased SOCS-3 expression and oxidative stress due to insulin resistance inhibit interferon alpha–mediated JAK-STAT signaling, leading to an inadequate host immune response to HCV, then treatment with the TZD drugs may improve response to interferon-based therapy. Prospective trials are needed to assess the effect of combination therapy with a TZD plus peginterferon and ribavirin on innate immunity and SVR.
In summary, adjunct therapies aimed at improving insulin sensitivity—both lifestyle modification and insulin-sensitizing medications—may hold the most promise for improving outcomes of hepatitis C therapy. Adequately powered studies designed to assess both innate immune response and SVR to antiviral therapy are urgently needed. Previous nonresponders to interferon-based therapy may also benefit from this type of approach, and future studies should include this group of patients. If the results of such studies are positive, future hepatitis C treatment regimens may be individually tailored according to a patient’s BMI and degree of insulin resistance as well as HCV genotype and stage of liver disease.
----------------------------------
I am scheduled to participate in this type study, so if you could help me from wasting my time, I would appreciate it.
...Pharmacologic agents that decrease insulin resistance provide another intriguing strategy for reducing steatosis and improving response to hepatitis C treatment. One class of medications, the thiazolidinediones (TZDs), improve insulin sensitivity through activation of the peroxisome proliferator-activated receptor-gamma (PPAR-γ) in adipocytes and skeletal muscle.[68] Pioglitazone, one of 2 currently available PPAR-γ ligands, decreases insulin resistance, lowers TNF-α levels, increases adiponectin levels (thereby, increasing PPAR-α ligand activity), and reduces hepatic steatosis in NASH patients.[69] Further, data suggest that pioglitazone also decreases SOCS-3 expression.[70] Ultimately, if increased SOCS-3 expression and oxidative stress due to insulin resistance inhibit interferon alpha–mediated JAK-STAT signaling, leading to an inadequate host immune response to HCV, then treatment with the TZD drugs may improve response to interferon-based therapy. Prospective trials are needed to assess the effect of combination therapy with a TZD plus peginterferon and ribavirin on innate immunity and SVR.
In summary, adjunct therapies aimed at improving insulin sensitivity—both lifestyle modification and insulin-sensitizing medications—may hold the most promise for improving outcomes of hepatitis C therapy. Adequately powered studies designed to assess both innate immune response and SVR to antiviral therapy are urgently needed. Previous nonresponders to interferon-based therapy may also benefit from this type of approach, and future studies should include this group of patients. If the results of such studies are positive, future hepatitis C treatment regimens may be individually tailored according to a patient’s BMI and degree of insulin resistance as well as HCV genotype and stage of liver disease.
----------------------------------
I am scheduled to participate in this type study, so if you could help me from wasting my time, I would appreciate it.
What misinformation? The insulin resistance drugs were not discussed here. But, seeing as how you brought it up..... My hep doc plans on putting me on one of these drugs after I drop at least 10% of body weight, (which I am acheiving). So, if you could be a little more specific on why these two doc's said it isn't a good idea, I'm all ears.
Sorry Gauf, but this may be misinformation here:
>>>>>>>*Studies are currently under way to assess the efficacy of both thiazolidinediones and metformin in combination with peginterferon plus ribavirin for patients with chronic HCV infection with insulin resistance and steatosis.>>>>>>>>>>
I was told by 2 docs metformin is NOT a good med to take with HCV.
Diet control, or insulin, or Byetta to slow starch absorption were choices given me.
Byetta is spendy and INS won't pay UNLESS you have liver disease in which case the other 3 oral meds are all contraindicated.
However, with HCV you should be able to get Byetta approved.
You can also slow your Bl sug. by taking in more fat in the meal and less carbs. Fat will slow the absorption time for all food groups, thereby reducing sugar spikes. Don't slather on the butter, or overdo, but for instance, take your vitamin A&D (natural codliver oil supplement) (essential to liver function and immune systems function AND diebetes) with one meal perhaps, then put some olive oil on your salad for dinner, this also aides in the RIBAvirin absorption
>>>>>>>*Studies are currently under way to assess the efficacy of both thiazolidinediones and metformin in combination with peginterferon plus ribavirin for patients with chronic HCV infection with insulin resistance and steatosis.>>>>>>>>>>
I was told by 2 docs metformin is NOT a good med to take with HCV.
Diet control, or insulin, or Byetta to slow starch absorption were choices given me.
Byetta is spendy and INS won't pay UNLESS you have liver disease in which case the other 3 oral meds are all contraindicated.
However, with HCV you should be able to get Byetta approved.
You can also slow your Bl sug. by taking in more fat in the meal and less carbs. Fat will slow the absorption time for all food groups, thereby reducing sugar spikes. Don't slather on the butter, or overdo, but for instance, take your vitamin A&D (natural codliver oil supplement) (essential to liver function and immune systems function AND diebetes) with one meal perhaps, then put some olive oil on your salad for dinner, this also aides in the RIBAvirin absorption
G3s are also prone to metabolic steatosis. This hangs around after SVR.
I agree with the DD approach. My Doc is at least prepared to listen. But then he would have been arguing with Shiffman rather than me. Take the Shiffman article with you next time and see what he says then.
CS
I agree with the DD approach. My Doc is at least prepared to listen. But then he would have been arguing with Shiffman rather than me. Take the Shiffman article with you next time and see what he says then.
CS
Weight does not have to even be a factor for G3's. G3's have a 74% chance of having nafld in any event. If you happen to be a chubb on top of it, well there ya go.
-------------------------------------
(What it does do is slow down the viral kinetics and makes us less likely to RVR.)
-------------------------------------
Good reason for us G3"s to DD, or try Alinia. Why my Hepotologist said no to both is stressing me out! Just had a cbc and wbc is low, platelets way low, rbc high. Portal hypertension is getting worse QUICKLY, and these docs just won't get aggreesive enough. I hate to have to start looking again, but I probably have just one last good shot before ESLD.
-------------------------------------
(What it does do is slow down the viral kinetics and makes us less likely to RVR.)
-------------------------------------
Good reason for us G3"s to DD, or try Alinia. Why my Hepotologist said no to both is stressing me out! Just had a cbc and wbc is low, platelets way low, rbc high. Portal hypertension is getting worse QUICKLY, and these docs just won't get aggreesive enough. I hate to have to start looking again, but I probably have just one last good shot before ESLD.
Doesnt it suck being a G2 or 3 when Tx fails us. We get lumped together and then have to find snipets from various studies and the join the dots.
One thing i would suggest is find out if you have steatosis. G2s are the least prone geno for fatty liver but its a definite negative for those that have it.
You may not need to see 180. There are studies that suggest that each 10 kgs (20 lbs) loss improves IR and steatosis and can even result in fibrosis regession.
btw with 2 positives lab error doesnt seem all that likely to me so i think you may be right.
CS
One thing i would suggest is find out if you have steatosis. G2s are the least prone geno for fatty liver but its a definite negative for those that have it.
You may not need to see 180. There are studies that suggest that each 10 kgs (20 lbs) loss improves IR and steatosis and can even result in fibrosis regession.
btw with 2 positives lab error doesnt seem all that likely to me so i think you may be right.
CS
There doesn't seem to be enough study on us chubbys or geno 2 so if this last test of mine is postive which I think it proably is. I'll take a different approach on my next treatment get the weight off before restarting make sure i'm getting the right dose for my weight. even if I get the weight off I don't think i'll ever see 180 again. I'm 6'4" last time I saw 180 was in high school.
Lynn
Lynn
Your treatment regime makes me depressed. Shouldn't a breakthrough after week 12 as a geno 2 be considered equal to a breakthrough after week 24 as a geno 1? Your case seems to verify this thought. I haven't read this anywhere, it just seems logical to me, being that a geno 2 is a slow responder if not UND until between week 5 and 12.
13-15 mg per kilo is an often mentioned figure for weight based dosing of ribavirin. For you (122.5 kg) 13 mg/kg would be 1600 mg riba. PegIntron should be dosed at 1.5 mcg/kg, which would leave you with 184 mcg PegIntron, and as said earlier in this thread max dose is 150 mcg which appears not to be enough for you. I also think it might very well be true that neither is 180 mcg Pegasys.
When are the chubby ones going to get a proper chance at beating this virus?
13-15 mg per kilo is an often mentioned figure for weight based dosing of ribavirin. For you (122.5 kg) 13 mg/kg would be 1600 mg riba. PegIntron should be dosed at 1.5 mcg/kg, which would leave you with 184 mcg PegIntron, and as said earlier in this thread max dose is 150 mcg which appears not to be enough for you. I also think it might very well be true that neither is 180 mcg Pegasys.
When are the chubby ones going to get a proper chance at beating this virus?
G3 steatosis is a different animal than for non 3 genos. For us we get it irrespective of other risk factors. Steatosis is also reduced and casn even diappear with SVR.
What it does do is slow down the viral kinetics and makes us less likely to RVR.
The 231 subjects by Westin and colleagues study referred to in the link above treated G3s for 48 weeks which is why it didnt find steatosis as a negative predict.
CS
What it does do is slow down the viral kinetics and makes us less likely to RVR.
The 231 subjects by Westin and colleagues study referred to in the link above treated G3s for 48 weeks which is why it didnt find steatosis as a negative predict.
CS
Pegasys isnt weight based because of the 40kda Peg molecule.
It isnt supposed to go wondering about every part of our bodies, unlike NPIA (non peg IFN).
In therory it stays in the blood stream and as everyone has roughly the same amount of blood
10 pints/6 liters or there abouts it doesnt need to be dosed by weight.
I think drofi posted something about this not long ago.
Doesnt explain why double Dosing works better in patients over 85 kgs though.
CS
It isnt supposed to go wondering about every part of our bodies, unlike NPIA (non peg IFN).
In therory it stays in the blood stream and as everyone has roughly the same amount of blood
10 pints/6 liters or there abouts it doesnt need to be dosed by weight.
I think drofi posted something about this not long ago.
Doesnt explain why double Dosing works better in patients over 85 kgs though.
CS
i'm less of a chubb but still a chubb and my ifn was too high. It has to be personalized, I think.
welderman: i am taking 1400 riba and weigh A LOT less than you (no insult, okay). I don't get that dose for you, other than the 2b part.
welderman: i am taking 1400 riba and weigh A LOT less than you (no insult, okay). I don't get that dose for you, other than the 2b part.
Im a chubb and i know some chubbs who have had svr ..I hope people will not be discouraged or feel like they dont have a chance of clearing just because they are overweight cause you can clear!!!
makes sense to me also
My Dr originally wanted to start me on peginterferon alfa-2b weight dosed because of my weight 270 lb's but my insurance would only approve peginterferon alfa-2a because I am a geno 2b. I'm on shot 30 and have had a pretty easy time very little sides so far. but I've always wondered if that wasn't because of my wieght. I got to undected at week 5 and was undected untill week 18 when i showed a count of 30. The dr had me retest and I was undected but because of weight and the one glich decided to do 48 weeks. I just got results from my blood work today for shot week 28 and my level was 89,000 so I either have a break thru or Dr. thinks lab messd up. doing retest will find out next week i guess. anyway I'm wondering know If I haven't wasted a bunch of time on to small a dose of peginterferon alfa-2a for my wieght. I'm taking 1200 mg of riba each day.
Lynn
My Dr originally wanted to start me on peginterferon alfa-2b weight dosed because of my weight 270 lb's but my insurance would only approve peginterferon alfa-2a because I am a geno 2b. I'm on shot 30 and have had a pretty easy time very little sides so far. but I've always wondered if that wasn't because of my wieght. I got to undected at week 5 and was undected untill week 18 when i showed a count of 30. The dr had me retest and I was undected but because of weight and the one glich decided to do 48 weeks. I just got results from my blood work today for shot week 28 and my level was 89,000 so I either have a break thru or Dr. thinks lab messd up. doing retest will find out next week i guess. anyway I'm wondering know If I haven't wasted a bunch of time on to small a dose of peginterferon alfa-2a for my wieght. I'm taking 1200 mg of riba each day.
Lynn
started both tx's at about 187 lbs, over 6 feet. So, I guess in a normal range. What makes sense to me (or really doesn't) is how the same amt of IFN for someone who weighs 105 is rx'ed for someone at 250.
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