High False-Negative Rate for Nonalcoholic Steatohepatitis in Extreme Obesity.

retrospective (46%) and prospective (28%) cohorts.We think the lower frequency of serum for antinuclear antibody positivity we found compared with the data from Volta et al is much less relevant among our findings. We studied only a small group of celiac disease patients as a control group, and our study was not designed to evaluate this aspect of celiac disease. Regarding the frequency of autoimmune disorders associated with NCWS, we underline that ours is the first singlecenter study designed to provide data on this point. The discrepancy between the frequency we observed (24% vs 29%) and that reported in the Italian multicenter study (14%) could be owing to the heterogeneity of the patients included in that study. In a brilliant editorial Lebwohl and Leffler have written, “in critical moments, men sometimes see exactly what they wish to see,” and it is evident that at the moment there is no agreement in the scientific community not only about NCWS pathogenesis, but even on its real existence. Although relevant in many ways, the Italian multicenter study probably suffered from the “negative preconception” of those centers skeptical about NCWS, a preconception that was amplified by the confuse diagnostic criteria and the lack of a double-blind challenge as diagnostic method. In contrast, it is certain that NCWS should be considered a heterogeneous condition as we first suggested some years ago, in which different kinds of patients with different pathogenesis of their wheat-related symptoms are still lumped together. Since the beginning of our interest in NCWS, we have focused on the patients who had an “immunologic characteristic”: food allergy in infancy, associated atopic disease, eosinophil or lymphocyte infiltration in the intestinal mucosa, and so on. Consequently, in the Rorschach test of sorts we view a strong immunologic basis for NCWS pathogenesis, but in the discussion section we warned readers about this possible bias of a highly selected study population. In conclusion, we feel that the “NCWS field” still remains a “fertile crescent” for research and in this respect, understanding the immunological path is the most promising, as suggested by our recent data, especially considering the possible role of amylase/trypsin inhibitors as activators of innate immunity.