Insulin resistance in prediction of esophageal varices^†

Insulin resistance (IR) is commonly associated with hepatitis C virus (HCV) infection, and development of IR can occur early in the course of HCV infection.1 The exact pathogenetic mechanisms responsible for this association are still unknown; however, they may be related to both HCV itself and to liver injury. Hence, IR is a major independent determinant of fibrosis in chronic HCV infection, regardless of the genotype and the severity of liver damage.2, 3 Both IR and beta-cell dysfunction contribute to glucose intolerance in patients with chronic HCV. In addition, IR may be the earliest abnormality in this process, which in the following years may progress to glucose intolerance and also diabetes mellitus (DM).4, 5 Thus, impaired glucose tolerance (IGT) has been reported in HCV-infected patients before the onset of cirrhosis. HCV infection also is associated with an increased prevalence of diabetes mellitus.6, 7 These data indicate the specific role of HCV in the evolution of impaired insulin action and IGT, independent from the development of cirrhosis.

In a recent issue of HEPATOLOGY, we read with great interest the article by Cammà et al. investigating the role of liver stiffness and IR in the noninvasive prediction of portal hypertension.8 In conclusion, they reported that IR, regardless of the presence of diabetes, significantly predicts the presence of esophageal varices (EV), in subjects with HCV-related cirrhosis. In order to reduce the need for endoscopic procedures, the development of a noninvasive tool for the prediction of presence of EV is an important issue in subjects with cirrhosis. So, this study is important because it provides scientific information on this relevant issue. However, we think that some points should be discussed.

First, as shown in Table 1 of the article, most of the study participants are overweight and some of them are even obese. Obesity is a strong risk factor for DM and also for IGT. Although it was stated in the article that 26% of the patients had diabetes at baseline, there is no information regarding the glucose tolerance status of the other subjects. As mentioned above, HCV per se is able to decrease insulin sensitivity and chronic HCV infection is associated with a high prevalence of glucose abnormalities. In light of these clear data, we think that some of the study participants may still have overt glucose dysregulation or DM without implementation of the glucose tolerance test. Therefore, matching the groups with and without EV only for glucose and body mass index levels may not be enough to make clear comparisons at this point, because DM and even glucose intolerance is itself a predictor of presence of IR. Moreover, plasma insulin levels differ according to the degree of glucose dysregulation.9 Second, as stated in the methods section of the article, the diagnosis of DM was based on the American Diabetes Association criteria, using fasting blood glucose levels of 126 mg/dL or greater on at least two occasions and ongoing treatment with hypoglycemic agents. However, apart from the insulin treatment, there is no detailed information about the use of glucose lowering agents. It is well known that measures of insulin sensitivity are easily affected by medications that are frequently prescribed in DM.10

Finally, we think all these points make the resultant comparisons and correlations questionable. Therefore, we would like to ask the authors whether they can present some new results by categorizing the subjects with HCV infection according to glucose tolerance. This may provide the readers clearer information about the role of IR in predicting the presence of EV in patients with HCV-related cirrhosis.