• Potential conflict of interest: Nothing to report.


We thank Dr. Manesis for his response and query raising the important point of normal ranges for laboratory values and their possible effect on the results of our study.1 The data for liver tests collected from our patients in both the control group and the patient group with Wilson disease were recorded at many different clinical sites at which the upper limits of normal differed. The only normalized value collected by this study was the international normalized ratio. Although we were also initially concerned about this problem, we found that despite the lack of uniformity for laboratory testing ranges or normalization of the test results to controls, the analyzed data showed clear cutoffs on analysis by receiver operated curves for our study groups. With respect to the age differences for laboratory ranges, we agree that the results for the alkaline phosphatase measurements would be the most dramatically affected. However, even with the inclusion of some pediatric patients in the Wilson disease group [four patients; 14 (n = 2), 15, or 17 years old] and none in the controls, only one of the pediatric patients had such a higher alkaline phosphatase value that the ratio of alkaline phosphatase to bilirubin was greater than 1 (it was 3.72); this still permitted a clear cutoff value of <4 in comparison with controls with acute liver failure of other etiologies (see Fig. 2 in Korman et al.1). We did not find differences in the range of laboratory tests or results for this study when the groups were analyzed by sex or age. Therefore, despite all the limitations inherent in using data from multiple laboratory sites and across sex and age, we believe that the results of our study are extremely applicable to our clinical practices.

Michael L. Schilsky M.D.*, William Lee M.D.*, Frank Wiands Ph.D.*, * Weill Cornell Medical Center New York, NY.