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
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
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