A lack of response to treatment for WD would be expected for CDG patients as well. In summary, Nicastro et al.’s data6 demonstrate that the approach of the current guidelines of the American Association for the Study of Liver Diseases to the diagnosis of WD, which calls for obtaining a slit lamp examination, a serum ceruloplasmin level, and a 24-hour urine copper level (and then liver biopsy in some) is useful even in young, clinically asymptomatic children. The

WD scoring system makes use of these data and helps clinicians to gauge the degree of certainty of the diagnosis. In addition, WD scores greater than 4 appear find more to be validated. Molecular testing for diagnosis has come of age and is perhaps the

new standard for family screening; at present, it is still expensive and not always obtainable for all patients, although it is commercially available. In the pediatric population with liver ailments, WD should be considered in patients with undefined disease, in those rare young patients with concurrent neurological problems, and in those patients Selleckchem Opaganib with a suboptimal response to therapy directed against another presumed liver disease (especially autoimmune hepatitis). As shown by this study, we can now “mine for copper” and for mutant genes in the very young and use the WD score to be more confident in establishing a correct diagnosis of WD. However, keeping our suspicion high and considering a diagnosis of WD before the “ore” or, more specifically, the copper creates irreversible cellular damage are critical to achieving better outcomes for patients with this treatable disorder. “
“Boulter L, Govaere O, Bird TG, Radulescu S, Ramachandran P, Pellicoro A, et al. Macrophage-derived Wnt opposes Notch signaling

to specify hepatic progenitor cell fate in chronic liver disease. Nat Med 2012;18:572-579. www.nature.com (Reprinted with permission.) During chronic MCE公司 injury a population of bipotent hepatic progenitor cells (HPCs) become activated to regenerate both cholangiocytes and hepatocytes. Here we show in human diseased liver and mouse models of the ductular reaction that Notch and Wnt signaling direct specification of HPCs via their interactions with activated myofibroblasts or macrophages. In particular, we found that during biliary regeneration, expression of Jagged 1 (a Notch ligand) by myofibroblasts promoted Notch signaling in HPCs and thus their biliary specification to cholangiocytes. Alternatively, during hepatocyte regeneration, macrophage engulfment of hepatocyte debris induced Wnt3a expression. This resulted in canonical Wnt signaling in nearby HPCs, thus maintaining expression of Numb (a cell fate determinant) within these cells and the promotion of their specification to hepatocytes. By these two pathways adult parenchymal regeneration during acute liver injury is promoted.