{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:55:53Z","timestamp":1791482153825,"version":"4.3.4"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2017,1,6]],"date-time":"2017-01-06T00:00:00Z","timestamp":1483660800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1"},{"start":{"date-parts":[[2017,1,6]],"date-time":"2017-01-06T00:00:00Z","timestamp":1483660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:p>\n                    Pediatric acute liver failure (PALF) is a potentially devastating condition that occurs in previously healthy children of all ages and frequently leads to a rapid clinical deterioration. An identified cause for liver injury is lacking in approximately 30% of cases. Children with undetermined diagnosis have lower spontaneous survival and higher rates of transplantation and death than other diagnostic groups. A single\u2010day workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases brought together clinicians and basic scientists to integrate aligned research findings and develop a foundation for new mechanistic studies and future treatment trials. The clinical phenotype of indeterminate PALF shares important similarities to the hyperinflammatory state characteristic of hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS). A failure of cytotoxic T cells to limit or contract inflammatory responses may propagate injury and lead to a local and systemic milieu that does not support normal hepatic regeneration. Evidence was presented that bone marrow (BM)\u2010derived\n                    <jats:underline>S<\/jats:underline>\n                    inusoidal endothelial cell\n                    <jats:underline>PRO<\/jats:underline>\n                    genitor\n                    <jats:underline>C<\/jats:underline>\n                    ells (sprocs) play a vital role in hepatic regeneration. Overwhelming systemic inflammatory responses may suppress mobilization of BM sprocs and dampen hepatic recovery.\n                    <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>\n                    : Experience gained through treatment trials of HLH and MAS in childhood may inform study design for therapy of PALF. Successful approaches to limiting neuroinflammation through reduction of systemic inflammation and standardized neuroprotection protocols that limit glial injury could significantly improve intact survival. Finally, given that PALF is a rare disease, investigative efforts must include broad multicenter collaboration and careful stewardship of biorepository specimens. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2017;65:1026\u20101037).\n                  <\/jats:p>","DOI":"10.1002\/hep.28944","type":"journal-article","created":{"date-parts":[[2016,11,14]],"date-time":"2016-11-14T14:13:25Z","timestamp":1479132805000},"page":"1026-1037","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":84,"title":["Pediatric acute liver failure of undetermined cause: A research workshop"],"prefix":"10.1097","volume":"65","author":[{"given":"Estella M.","family":"Alonso","sequence":"first","affiliation":[{"name":"Department of Pediatrics,Ann & Robert H. Lurie Children's Hospital of Chicago,Chicago,IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon P.","family":"Horslen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics at the University of Washington School of Medicine,Seattle Children's Hospital,Seattle,WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward M.","family":"Behrens","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,Children's Hospital of Philadelphia, University of Pennsylvania,Philadelphia,PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Doo","sequence":"additional","affiliation":[{"name":"Liver Diseases Research Branch,National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of 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