Hepatitis C in nonobese nondiabetic patients: Insulin resistance and the metabolic syndrome make a difference

To the editor: We read with an increased interest the article of Gonzales et al.,1 regarding the factors associated with insulin resistance (IR) in nondiabetic hepatitis C patients. Chronic hepatitis C (CHC) has many features placing it also in the group of metabolic diseases, involving IR2 and high prevalence of steatosis.3 The prevalence of the metabolic syndrome (MS) is also increased in these patients4, but the question whether MS and IR are only related to obesity and diabetes or are a feature of the infection itself still stands. As many features of MS are also related to ethnicity, we investigated whether the findings of Gonzales et al. could be reproduced in a cohort of exclusively Caucasian patients with CHC. Therefore, we evaluated the prevalence of MS and IR, as well as the inflammatory features (IL6, CK18) and adipocytokinic profile in 150 consecutive, biopsied patients with genotype 1 CHC, without obesity or diabetes. The mean age was 45.77±11.45, with no sex difference (P=.65). MS was found in 10% of patients. We did not find a significant correlation of MS with gender (P=.46), but the age seems to be important, as suggested by the higher rate of MS in patients over 50 (P=.03). Furthermore, the difference remains when dividing female patients into two groups at the cutoff of 50 years: the highest prevalence of MS was found in men, followed by females over 50, and then females under 50 (P=.04). Patients with MS were insulin resistant, with a mean HOMAIR above 4 (5.82±3.43 vs 2.86±1.75, P=.008). The adipocytokine profile identified a higher level of leptin (34 823.38±23 418.34 vs 22 755.05±18 208.02; P=.01) in the MS group, while no significant differences were found for adiponectin (P=.31). The liver biopsies revealed increased grades of steatosis (P=.009) and necroinflammatory activity (P=.02) in the MS group. As far as IR is concerned, we did not find a significant association with gender (P=.21) or age (P=.47), but our study excluded the obese patients, as compared with the study by Gonzales et al. in which only diabetic patients were excluded. Abdominal obesity (88.50±9.56 vs 85.221±11.44, P=.05) and overweight (P=.05) were associated with IR. As regards the adipokines, neither the adiponectin (P=.10) nor the leptin (P=.51) levels were associated with IR, suggesting that the changes in the adipocytokine profile reported in CHC may be related to obesity and MS. Interestingly, the IL6 levels were higher in patients with IR (2.40±1.94 vs 1.54±0.87; P=.006), showing a tendency for correlation between IR and inflammation. We also found higher levels of CK18 in patients with IR (586.4±190.36 vs 439.18±141.07; P=.02), confirming a significant association with hepatocyte necrosis.5 In conclusion, our data—generated from a cohort of Caucasian nonobese nondiabetic HCV patients, are partly in the favour of the findings of Gonzales et al., showing an influence of age and gender on the presence of MS, but not that of IR. The results may be different when taking into account the differences in race (Caucasian in our research) and the exclusion of obesity in our study. In nonobese nondiabetic HCV patients, IR and MS are important parameters with consequences on necroinflammation and steatosis. These findings strengthen the necessity for nutritional advice, even in nonobese patients, for the prevention of overweight and IR.