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We read with great interest the recent paper from Piche and colleagues (Gut 2002;51:434–9) relating leptin levels to fatigue in chronic hepatitis C patients. On the surface, their observation that serum leptin levels correlate with the fatigue impact scale are very intriguing. However, leptin shows a gender based difference and women have circulating plasma leptin concentrations that are at least three times higher than men, even when matched for body fat mass.1 Thus sex needs to be considered when investigating any association with leptin levels, and multivariate analysis is necessary to reduce the bias caused by this confounding variable. Indeed, in the study by Piche et al the fatigue impact scale was found to be significantly higher in females. Therefore, without a multivariate analysis the authors cannot affirm that serum leptin levels are implicated in fatigue development in patients with chronic hepatitis C.
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