Adipokines and insulin resistance in chronic hepatitis C
Authors: Emmanuel Tsochatzis, George V. Papatheodoridis, Athanasios J. Archimandritis
Journal: Hepatology (2007)

We read with great interest the study by Cua et el. concerning the associations of adipokines with insulin resistance (IR) and liver injury in chronic hepatitis C (CHC),1 because the potential role of adipokines in the pathogenesis of chronic liver diseases and especially CHC and nonalcoholic fatty liver disease is a focus of current research.2 Although it is a meticulous study, we feel that it does not undoubtedly prove that hepatitis C virus–associated IR is an adipokine-independent effect. The authors reached such a conclusion because patients with CHC with low fibrosis compared to their matched controls were found to have significantly higher scores of homeostasis model assessment of insulin resistance (HOMA-IR) without significant difference in serum adipokine concentrations. However, the researchers detected independent associations of leptin and adiponectin levels with IR in patients with CHC. They stated that body mass index (BMI), leptin, and adiponectin accounted for 37% of the variability of HOMA-IR in the CHC cohort without providing a similar analysis in the control group; thus, the factors associated with IR in controls cannot be determined. Moreover, they used a linear model to identify predictors of IR. Although HOMA-IR was significantly higher in patients with CHC, its mean value was only 2.12, which is much lower than what is considered indicative of IR (≥3.0 or even higher cut-off levels).3 Therefore, the clinical significance of the difference in the HOMA-IR index between patients with CHC and controls may be questionable. A qualitative comparison between the 2 groups with the cases classified according to a HOMA-IR cut-off value of 3.0 might be more meaningful and informative. In our unpublished, prospective CHC cohort currently including 70 naive patients, we also determined the associations of serum leptin, adiponectin, and resistin levels with HOMA-IR and liver histology analysis. We included patients with CHC with genotypes 1, 3, and 4, which has a “metabolic” steatotic profile similar to that of genotype 1 according to our data.4 The baseline characteristics of our patients appear in Table 1. In univariate analysis, presence of IR, defined as HOMA > 3.0, was associated with increasing BMI (P = 0.05), male sex (P = 0.009), and lower adiponectin levels (P = 0.001) but not with leptin or resistin levels, genotype, viral load or histological severity. In logistic regression analysis, presence of IR was independently associated with increasing BMI (OR: 1.203; 95% CI: 1.008-1.437), male sex (OR: 4.340; 95% CI: 1.298-14.511) and lower serum adiponectin levels (OR: 0.837; 95% CI: 0.732-0.956). The association of adiponectin levels with IR is in agreement with the findings of Cua et al. In contrast, we did not find an association of leptin with IR, similar to previous reports,5, 6 although a type II error cannot be excluded. We also failed to show a relation between IR and resistin, which has not been clearly associated with IR and obesity in humans, as correctly stated by the authors as well. In conclusion, the pathogenesis of IR in CHC is an intriguing field of current research with new and sometimes conflicting emerging data. Adipokines represent potential mediators in this process and thus their role needs further investigation. Emmanuel Tsochatzis*, George V. Papatheodoridis*, Athanasios J. Archimandritis*, * Second Department of Internal Medicine, Athens University Medical School, Hippokration General Hospital, Athens, Greece.