{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:56:29Z","timestamp":1791507389239,"version":"4.3.4"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2018,7,23]],"date-time":"2018-07-23T00:00:00Z","timestamp":1532304000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2018,7,23]],"date-time":"2018-07-23T00:00:00Z","timestamp":1532304000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:p>\n                    The cause of pediatric acute liver failure (PALF) is unknown in up to 40% of cases. Evidence suggests that aberrant immune system activation may play a role. We hypothesized that indeterminate PALF cases would exhibit a unique pattern of hepatic inflammation. This was a retrospective and prospective study of PALF cases due to indeterminate (iPALF), autoimmune hepatitis, or known diagnosis (dPALF) etiology. Liver tissue sections were stained with immunohistochemical markers for cytotoxic T\u2010cells (cluster of differentiation 8 [CD8]), perforin, and tissue resident memory T\u2010cells (CD103) and scored as minimal, moderate, or dense. Lymphocytes were isolated from liver tissue for T\u2010cell receptor beta sequencing and flow\u2010cytometric studies. Thirty\u2010three iPALF, 9 autoimmune hepatitis, and 14 dPALF cases were included. Dense hepatic infiltrates of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cells were found in 27 (82%) iPALF cases compared to 1 (7%) dPALF case (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; 0.0001). Perforin staining was dense or moderate in 19 (73%) of 26 iPALF cases compared to minimal in all 7 dPALF cases (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 0.004); 16 (62%) of 26 iPALF cases had dense CD103 staining compared to none of the 6 dPALF cases (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 0.001). T\u2010cell receptor beta sequencing of iPALF cases demonstrated increased clonality compared to dPALF and control cases. Flow cytometry and immunohistochemistry revealed that iPALF intrahepatic leukocytes were predominantly tissue resident memory CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cells.\n                    <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>\n                    : Indeterminate PALF is characterized by a dense CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell hepatic infiltrate consistent with expansion of a tissue resident memory T\u2010cell phenotype; CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cells are a biomarker of immune dysregulation in iPALF and may be used to better identify and define this group. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2018).\n                  <\/jats:p>","DOI":"10.1002\/hep.29901","type":"journal-article","created":{"date-parts":[[2018,3,30]],"date-time":"2018-03-30T22:00:01Z","timestamp":1522447201000},"page":"1087-1100","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":76,"title":["Indeterminate pediatric acute liver failure is uniquely characterized by a CD103+CD8+ T\u2010cell infiltrate"],"prefix":"10.1097","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3339-9372","authenticated-orcid":false,"given":"Catherine A.","family":"Chapin","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Northwestern University, Feinberg School of Medicine,Ann & Robert H. Lurie Children's Hospital of Chicago,Chicago,IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Burn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pennsylvania, Perelman School of Medicine,The Children's Hospital of Philadelphia,Philadelphia,PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Meijome","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pennsylvania, Perelman School of Medicine,The Children's Hospital of Philadelphia,Philadelphia,PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen M.","family":"Loomes","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pennsylvania, Perelman School of Medicine,The Children's Hospital of Philadelphia,Philadelphia,PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector","family":"Melin\u2010Aldana","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Northwestern University, Feinberg School of Medicine,Ann & Robert H. Lurie Children's Hospital of Chicago,Chicago,IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Portia A","family":"Kreiger","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine,The Children's Hospital of Philadelphia,Philadelphia,PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter F.","family":"Whitington","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Northwestern University, Feinberg School of Medicine,Ann & Robert H. Lurie Children's Hospital of Chicago,Chicago,IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward M.","family":"Behrens","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pennsylvania, Perelman School of Medicine,The Children's Hospital of Philadelphia,Philadelphia,PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estella M.","family":"Alonso","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Northwestern University, Feinberg School of Medicine,Ann & Robert H. Lurie Children's Hospital of Chicago,Chicago,IL"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2018,7,23]]},"reference":[{"key":"hep29901-bib-0001-20251105","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/j.jpeds.2005.12.051","article-title":"Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group","volume":"148","year":"2006","journal-title":"J Pediatr"},{"key":"hep29901-bib-0002-20251105","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.jpeds.2009.06.005","article-title":"Pattern of diagnostic evaluation for the causes of pediatric acute liver failure: an opportunity for quality improvement","volume":"155","year":"2009","journal-title":"J Pediatr"},{"key":"hep29901-bib-0003-20251105","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1097\/MPG.0000000000000512","article-title":"Analysis of viral testing in nonacetaminophen pediatric acute 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