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Nursey's Corner
Help for Hep C Patients


Silvia Hinojosa-Price, RN, corresponds with Dr. Zobair Younossi, M.D., M.P.H. Director, Center for Liver Diseases, Medical Director, Liver Transplant Program, with questions related to insulin resistance in advanced liver disease, as well as lower response to antiviral therapy. 


Dr.
Younossi,
I have several questions related to the subject of insulin resistance.

Based on the information about insulin resistance lowering SVR, I would like to know how many of you test for insulin resistance and use insulin sensitizers even though the patient may not be diagnosed as a diabetic yet--just insulin resistant.  If so, what are you using, and have you seen any toxic effects from glitazones?

Since the HCV damages the mitochondria by a process of oxidative stress and the same may be true for insulin resistance, are you recommending anti-oxidants and if so, what amount?

Since aerobic exercise helps produce more mitochondria and a high- protein diet boosts the benefit of exercise, possibly decreasing insulin resistance, are you recommending compensated patients do this and if so, how much protein?

As a diabetes educator, I find the subject of insulin resistance
fascinating. Thank you for your input.

Sources:
Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15765399&query_hl=1 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15765399&query_hl=1

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14976002&dopt=Citation


Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14976002&dopt=Citation

Liver steatosis is an independent risk factor for treatment failure in patients with chronic hepatitis C.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15674091&dopt=Citation
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15674091&dopt=Citation


Protein-rich diet boosts benefit of exercise.
http://www.eurekalert.org/pub_releases/2005-08/epr_pdb082505.php


RESPONSES TO DATE (9/15/05):

The issue of metabolic syndrome in patients infected with HCV is quite interesting.
It seems that HCV patients with components of metabolic syndrome (diabetes mellitus, central obesity, insulin resistance) can have more advanced liver disease as well as lower response to antiviral therapy.  The exact mechanism of this interaction is not well known but could involve insulin resistance (IR), adipokines (adiponectin, leptin), cytokines, and associated oxidative stress.

Despite this interesting data, I don't routinely check HCV patients  for IR.  However, assessing IR in patients with nonalcoholic disease (NAFLD), a fasting serum glucose and serum insulin can provide an easy method to calculate HOMA (HOMA >2.2=IR).


Although theoretically it makes sense to use medications/ strategies to improve IR and oxidative stress, there are currently no convincing data that these treatment strategies (including amount of protein intake) improve outcomes in patients with HCV.

However, for overweight HCV patients, I do recommend gradual weight loss. .....


Zobair Younossi, MD, MPH
Director, Center for Liver Diseases
Medical Direcor, Liver Transplant Program
Inova Fairfax Hospital
Co-Director, Center for the Study of Genomics in Liver Diseases
Affiliate Professor of Biomedical Sciences
George Mason University
Fairfax, Virginia
.

UPDATE:

It worked! Adding Metformin to Peg-Interferon and Ribavirin, espically before treating, increased odds for clearing Hepatitis C. More patients achived a Substaind Viral Response (SVR) with Metformin.
 
...123 patients and 22 discontinued because of non-compliance, stopping before week 24, lost to follow-up, etc. Of the 101 that finished the study, SVR was 67.4% for the Metformin group vs 49.1% for the Peg+Riba group...
 
AND... the study show if a higher dose of Metformin was used from the start. (study used 425mg three times a day x4 weeks then increased it to 850mg three times a day) and taken before treatment...  could prompt even better SVR results.
 
And so....
 
Insulin Resistance now becomes the new PREDICTOR for SVR (independent of genotype and fibrosis stage).....finally.
 
Quote from article below: "Women have more fat stores," Dr. McCullough explained. "Metformin improves their response, but at 57.7%, response rates are still low, overall." "Many patients with chronic HCV infection have insulin resistance," noted Dr. McCullough. "Fat in the liver inhibits response to antiviral therapy. Increasing insulin sensitivity should improve response to treatment."

http://www.docguide.com/news/content.nsf/news/852571020057CCF6852574F60061DC6D
Metformin Improves Antiviral Response Rates in Chronic Hepatitis C: Presented at AASLD
By Em Brown
 
SAN FRANCISCO -- November 3, 2008 -- Patients with chronic hepatitis C virus (HCV) infection who have responded poorly to standard antiviral treatment in the past may get a bump in viral response rates if the antidiabetic agent and insulin sensitiser metformin is added to pegylated interferon (PEG-IFN) alfa-2a and ribavirin, according to findings presented at the Liver Meeting 2008, the 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).

 

 

Do You Have Insulin Resistance? Increase Interferon treatment odds at a "Sustained Viral Response" (SVR-clearing the virus! ) 

Note to all: Most doctors are not aware the roll IR plays or how to compute HOMA. Check his work, and take this info with you when seeking advice.
 
HOMA is a formula that uses the results of 2 blood tests ....a FASTING INSULIN and FASTING GLUCOSE (sugar) to figure out if you're insulin resistant.
 
(Fasting Insulin X Fasting Glucose, Divided by 22.5)
 
 
A HOMA result of < 2 is considered NORMAL.

In genotype 1, studies have shown that the more insulin resistant you are, the lower the SVR....
 
HOMA < 2  SVR 60.5%
HOMA between 2-4   SVR 40%
HOMA > 4  SVR 20%
 

MUST READ!
Insulin resistance is a cause of steatosis and fibrosis progression in chronic hepatitis C  ...insulin resistance is the cause rather than the consequence of steatosis and fibrosis in genotype 1 patients...
 

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