e., two to three cases per year).33, 34, 36, 183, 184 These single-center reports all derive from transplant affiliated programs, so one must assume a bias toward more severe cases. This is especially relevant when considering issues related to prognosis. Development of an evidence based approach to the diagnosis and management of PSC in children is especially problematic given this relatively limited published data and an absence of controlled therapeutic trials.

Thus pediatric hepatologists are reliant on data derived from experiences with adult patients, although caution must be exercised in application of these approaches. An urgent need exists for prospective multi-centered studies of PSC in children. A number of lines of evidence suggest that PSC in children is different and not just an earlier stage in the disease process. Firstly, Selleck Ibrutinib some inherited diseases and immunologic defects may produce a clinical picture like PSC. These entities usually present clinically during childhood and may have an expanded spectrum of disease, which includes milder variants that when unrecognized are labeled as PSC. For example, mild to moderate defects in the ABCB4 (MDR3) gene are a likely cause of a number of cases of small duct PSC in children.185, 186 Stem Cells inhibitor Secondly, overlap syndrome of autoimmune hepatitis and PSC appears to

be significantly more common in children. In some centers evaluation of the biliary system is a standard part of the evaluation of all children with autoimmune hepatitis and those with biliary disease are diagnosed as having autoimmune sclerosing cholangitis (ASC). In these centers ASC is felt to be part of a broad spectrum of autoimmune liver disease in children.36 The exact criteria for diagnosis of autoimmune overlap in PSC are not well defined nor prospectively correlated with clinical course and/or therapeutic response. Next many reports show that children with PSC have higher serum ALT/AST and gamma glutamyltranspeptidase (γGTP) levels than their adult counterparts. This has been interpreted to be evidence of a distinct disease Doxorubicin process. Finally, many of the important and potentially life-threatening

sequelae of PSC, such as cholangiocarcinoma, are rarely observed in childhood.187 Thus many of the clinical approaches taken in adults related to these issues are of less importance in children. Measurement of γGTP is important in identifying potential biliary disease in children, in light of elevated levels of alkaline phosphatase associated with bone growth.188 Serum aminotransferase elevations may be more significantly elevated in children.189 MRC is an appropriate first biliary imaging approach in children and often circumvents the need for ERC.190 Liver biopsy may be of greater relevance in children, especially as it pertains to diagnosis of small duct PSC and in the identification of histologic features of autoimmune or immune-mediated disease.