Insulin resistance impairs response to hepatitis C therapy for patients co-infected with HIV

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Insulin resistance is associated with an impaired response to hepatitis C therapy for HIV-positive patients, Spanish investigators report in the online edition of the Journal of Acquired Immune Deficiency Syndromes.

“Our findings suggest that insulin resistance is an important determinant of poor response to anti-HCV [hepatitis C virus] therapy in HIV/HCV-coinfected patients”, comment the authors.

Recommended treatment for hepatitis C consists of pegylated interferon and weight-dosed ribavirin. The aim of therapy is an undetectable hepatitis C viral load 24 weeks after the completion of treatment. This is called a sustained virological response.

Glossary

insulin

A hormone produced by the pancreas that helps regulate the amount of sugar (glucose) in the blood.

pegylated interferon

Pegylated interferon, also known as peginterferon, is a chemically modified form of the standard interferon, sometimes used to treat hepatitis B and C. The difference between interferon and peginterferon is the PEG, which stands for a molecule called polyethylene glycol. The PEG does nothing to fight the virus. But by attaching it to the interferon (which does fight the virus), the interferon will stay in the blood much longer. 

fibrosis

Thickening and scarring of connective tissue. Often refers to fibrosis of the liver, which can be caused by an inflammatory reaction to long-term hepatitis infection. See also ‘cirrhosis’, which is more severe scarring.

body mass index (BMI)

Body mass index, or BMI, is a measure of body size. It combines a person's weight with their height. The BMI gives an idea of whether a person has the correct weight for their height. Below 18.5 is considered underweight; between 18.5 and 25 is normal; between 25 and 30 is overweight; and over 30 is obese. Many BMI calculators can be found on the internet.

glucose

A simple form of sugar found in the bloodstream. All sugars and starches are converted into glucose before they are absorbed. Cells use glucose as a source of energy. People with a constant high glucose level might have a disease called diabetes.

However, many patients do not achieve this outcome, and a poorer response to hepatitis C therapy is seen in HIV/hepatitis C-co-infected individuals.

Others factors associated with a lower chance of achieving a sustained virological response include hepatitis C genotype, hepatitis C viral load, fibrosis stage, and age.

Some research has suggested that the presence of insulin resistance also impairs responses to hepatitis C therapy. To gain a clear understanding of this issue, investigators from the HIV outpatient clinic of the Gregorio Maranon Hospital in Madrid performed a retrospective analysis involving 134 patients treated for hepatitis C between 2000 and 2007.

For each patient an insulin resistance score was calculated using the homeostatic model assessment (HOMA) method. An insulin resistance score was obtained using the following formula: fasting plasma glucose was multiplied by fasting serum insulin and divided by 22.5. Insulin resistance was diagnosed when a patient had a score of 3.8 of higher.

Most of the patients (77%) were men, and the median age was 40 years. The majority of patients (67%) were infected with the harder to treated hepatitis C genotypes – 1 and 4. In the majority of cases (81%) hepatitis C therapy included pegylated interferon.

The median HOMA-insulin resistance score was 2.5, and 31% of patients were diagnosed with insulin resistance.

Baseline insulin resistance scores were significantly lower for patients who achieved a sustained response to hepatitis C therapy than those who did not (1.9 vs. 3.3, p = 0.005).

Statistical analysis showed that the factors associated with achieving a sustained response to treatment included infection with the easier-to-treat genotypes 2 and 3 (OR = 6.7; 95% CI, 2.71-16.98, p < 0.001), and the absence of insulin resistance (OR = 3.3; 95% CI, 1.36-9.26, p = 0.008).

These findings were unaltered when the investigators controlled for age, gender, body mass index, type of interferon used in therapy, and fibrosis stage.

Moreover, the investigators found that even after controlling for potentially confounding factors, the presence of insulin resistance was associated with a poorer virologic response to hepatitis C therapy at weeks 4, 12, 24, 48, and 72.

“HOMA-insulin resistance should be included in the routine baseline evaluation of HIV/HCV-coinfected patients who are candidates for treatment with interferon and ribavirin”, conclude the investigators.

References

Ryan P et al. Insulin resistance impairs response to interferon plus ribavirin in patients coinfected with HIV and hepatitis C virus. J Acquire Immune Defic Syndr, advance online publication, 2010.