Terminology AT III inhibits serine proteases involved in the coagulation cascade. Additionally, AT III is reported to inhibit activation of inflammatory signaling cascades, including the activation of nuclear factor-��B, production of tumor necrosis inhibitor Wortmannin factor-�� and interleukin-6 in various cell types. Peer review The manuscript is clearly written and the authors discuss their findings in an adequate way. Moreover, the reduction of the dose of AT III via injection in the portal vein has clinical implications. Footnotes Peer reviewer: Dr. Georg Alexander Roth, Medical University of Vienna, General Anesthesia and Critical Care, Waehringer Guertel 18-20, Level 9I, Vienna A-1090, Austria S- Editor Gou SX L- Editor Kerr C E- Editor Zhang DN
Hypovitaminosis D is prevalent and may be encountered more frequently among children with inflammatory bowel disease (IBD) compared with healthy peers (1�C4).

Vitamin D exerts anabolic effects on bone (5) and may play a role in improving bone health in children with IBD (6). This vitamin is also involved in the regulation of the immune system (7), and it may play a role in the pathogenesis of IBD (8) and as an adjunct to treatment. In pediatric populations, serum 25-hydroxyvitamin D (25OHD) concentration greater than 20 ng/ml is considered ��sufficient�� based on rickets prevention (9). However, studies in adults have shown that PTH levels begin to plateau and intestinal calcium transport is maximized when serum 25OHD concentration is at least 32 ng/ml (10, 11).

Mechanisms responsible for suboptimal vitamin D status that may be amplified in children and adolescents with IBD include: decreased vitamin D intake from foods and supplements, decreased intestinal absorption, and increased loss through an inflamed intestine. Studies have identified upper gastrointestinal involvement, disease severity, and compromised nutritional status as risk factors for hypovitaminosis D in this population (1, 3). Guidelines for the treatment of vitamin D insufficiency (serum 25OHD concentration <20 ng/ml) in healthy children include the use of a wide range of cumulative vitamin D doses (84,000 to 600,000 IU) and recommend the higher doses for adolescents (9). There are no studies examining the efficacy and safety of any regimen for the treatment of vitamin D insufficiency in children with IBD. We hypothesized that: 1) doses in the higher end of the proposed spectrum are needed for this purpose, given that this disease preferentially afflicts adolescents, and disease-specific factors may reduce the bioavailability of vitamin D; and 2) vitamin D3 is more efficacious than vitamin D2, in accordance with the Brefeldin_A literature (12, 13).