• Conflict of interest: Nothing to report.


We thank Tietge and colleagues for their interest in our recent study on the role of adiponectin in the pathogenesis of nonalcoholic steatohepatitis (NASH).1 They provide data to support our conclusion that hypoadiponectinemia is a key feature of NASH. In addition, Tietge and collegues draw attention to the possible role of central obesity in the pathogenesis of this condition. We clearly recognized that central obesity was a critical determinant of the adipokine levels as indicated in our conclusion that “hypoadiponectinemia and elevated HOMA-IR (insulin resistance by homeostasis model) …… may be one of the pathogenic links between central obesity and the development of necroinflammatory forms of NAFLD”.1 The focus of our study was to determine the alterations in adipokine levels in NASH and their relationship to the severity of histological changes. The possible role of visceral obesity as the causative factor for insulin resistance and hypoadiponectinemia has been established in previous studies2–4 and this point was not further highlighted in our study.

Tietge et al. use waist-to-hip ratio as an indirect measure of visceral fat mass and demonstrate that subjects with NASH has a greater extent of visceral obesity compared to control subjects matched by percent body fat. Similar results have been published previously in a study which used single slice computed tomography (CT) to directly measure visceral obesity.5 However, the comparison between subjects with NASH and matched controls does not justify the proposition by Tietge et al. that “transition towards a hepatic inflammatory response and the development of NASH within a fatty liver are dependent on a shift in body fat distribution”. A more appropriate study to assess the role of central obesity in the development of the necroinflammatory response is to compare patients with NASH to those with simple steatosis who are matched by percent body fat. We measured body composition using dual energy x-ray absorptiometry in 37 of our 109 subjects (28 with NASH and 9 with simple steatosis).6 The subjects with NASH were of similar age (47.2 ± 13.0 vs. 44.9 ± 14.6 years), gender proportion (male/female: 20/8 vs. 7/1), body mass index (31.1 ± 4.8 vs. 30.9 ± 4.0 kg/m2), and percent body fat (35 ± 8 vs. 35 ± 9 %) compared with those with simple steatosis (results expressed as mean ± SD). Despite the similar degree of overall obesity, there was a trend toward increased central obesity in subjects with NASH compared to those with simple steatosis as indicated by the waist-to-hip ratio (WHR) (Fig. 1, P = .1, Mann-Whitney U test). These data support the hypothesis that visceral obesity may underlie the metabolic alterations which precipitate a necroinflammatory response in the fatty liver. Our findings need to be validated in a larger cohort. Direct measurement of visceral mass by computed tomography7 or magnetic resonance imaging8 will provide a more accurate assessment of the relationship between the fat compartments, the biochemical milieu and the histological features of NASH.

Figure 1.

Box-plot representation of waist-to-hip ratio (WHR) in subjects with nonalcoholic steatohepatitis (NASH) compared to those with simple steatosis matched by age, gender, body mass index, and body fat percent. The horizontal bar indicates the median values and 50% of values (i.e, between 25th and 75th percentiles) are within the box.

Jason M. Hui*, Jacob George*, * Storr Liver Unit, Westmead Millennium Institute, Westmead Hospital, Westmead, NSW 2145, Australia.