Insulin normally will trigger metabolic responses when it is released in normal quantities. If the insulin levels in blood are present beyond the required levels, the condition might result in insulin resistance (IR). Insulin resistance prevents the stimulation of usual metabolic responses. A previous study has revealed that the metabolic syndrome in liver called as non-alcoholic fatty liver disease is primarily caused by insulin resistance. There are several studies saying that insulin resistance is a common condition observed in chronic hepatitis C patients having genotypes 1 and 4. The direct relationship between the chronic hepatitis C and insulin resistance was proved in a study where insulin resistance appeared without any hepatic injury. Some studies have reported that insulin resistance has the ability to increase hepatic fibrosis and liver inflammation accompanied with the imbalanced response towards antiviral treatment.

The evaluation of insulin resistance was done using a glucose clamp technique which is considered as costly and strenuous. Another method which is found to be similar to the glucose clamp technique was the homeostasis model assessment (HOMA) which is utilized for assessing insulin sensitivity. HOMA was found to be comparatively less expensive.

Early virological response

In the case of early virological response, the viral load of hepatitis C will be reduced by 99 percent after HCV treatment is given for 12 weeks. The immediate response of the patient for HCV treatment is measured with EVR. The treatment for HCV is usually stopped if EVR in them is low or negligible.

This study discusses about the influence of insulin resistance on early virological response due to the hepatitis C virus treatment in HCV patients.

Experimental methodology

National Liver and Tropical Disease institute patients suffering from HCV infection were evaluated for the study. The patients were started with the treatment using oral ribavirin at the dosage of 1000 or 1200 mg/day). They are also given with pegylated interferon Alfa-2a at the dosage of 180 micrograms/week. The investigators were keen to evaluate the early virological response and its association with insulin resistance. EVR is determined by the absence of HCV RNA after 12 weeks of antiviral treatment.

The measurement of insulin resistance was done using homeostasis model of IR (HOMA-IR). If the value of HOMA-IR is greater than 2 then he or she is said to have insulin resistance.

HOMA-IR = fasting glucose (mmol/L) X fasting insulin (uU/ml) / 22.5.

The RNA of HCV was measured prior to and after 12 weeks of treatment.

Depending on the Ishak score, the extent of fibrosis activity and necro inflammatory activity were calculated through ultrasound led liver biopsy procedure.

Results of the study

The viral load was classified into three categories <106 copies/ml, 106 - 108 copies/ml, >108 copies/ml. The first category was called as mild, the second as moderate and the third as severe. Mild viral load was observed in 34 patients, moderate load in 24 patients and severe load in 18 patients.

Insulin resistance was observed to be present in 31 patients with its value as greater than 2. IR was evaluated by HOMA-IR test which showed the values ranging from 0.2 to 12.8. The mean of these values turned out to be 2.6.

Histo-pathological observations

The assessment of liver biopsy has revealed that the score of necro-inflammation ranged between 6 and 14 and the mean value of the necro inflammation was 10.7+/- 2.0.

The percentage of hepatocytes consisting of macro vesicular fat droplets was scored as Liver Steatosis. These values ranged between 20 percent and 55 percent with the mean value of 41 percent. The grade 1 steatosis was observed in 12 people, grade 2 and 3 was observed in 64 people.

Liver fibrosis stages ranged between 1 and 3. There were 22 patients with grade 1 and 2 fibrosis. Grade 3 fibrosis was present in 54 patients. The EVR was shown by 37 patients. The researchers attempted to find the difference between patients with IR<2 and those with IR>=2. No significant difference in Early virological response was observed. The liver steatosis percentage was found to be non-significantly higher in patients with IR greater than 2.

The researchers also could identify the positive correlation between insulin resistance and degree of hepatic steatosis; between IR and age. When the relationship between liver steatosis and necro-inflammation was checked, the average of the liver steatosis percentages were found to be significantly (p=0.0001) higher in patients with grade 3 and grade 4 fibrosis (43.2+/-7.8 percent) compared to the patients with grade 1 and grade 2 (35.4+/-8.1 percent) stages.

The correlation (p=0.0001) between Liver steatosis and necro-inflammation was 0.684. When the above parameters were studied in association with their response to treatment, only low age, fibrosis at lower stages, and lower BMI values were able to predict good early virological response. Direct correlation between Liver Steatosis and IR was established in this study while IR was found to have an indirect association with Liver fibrosis and Liver inflammation.


Wafaa M. Ezzat, Yasser A. Elhosary, Nour A. Abdulla, Hala M. Raslan, Omneya M. Saleh, Mona H. Ibrahim, Maha A. Rasheed, H. El-Hariri. Insulin resistance and early virological response in chronic HCV infection. Journal of Genetic Engineering and Biotechnology (2013) 11, 69-73.

About Author / Additional Info: