{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T05:02:42Z","timestamp":1784350962671,"version":"3.55.0"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. pediatr. gastroenterol. nutr."],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background and Aims:<\/jats:title><jats:p>Giant cell hepatitis with autoimmune hemolytic anemia (GCH\u2010AHA) is presumed to be an autoimmune disease, but the mechanism of liver injury is unknown. We proposed that in CGH\u2010AHA, the humoral limb of autoimmunity is the dominant force driving progressive liver injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p>We studied 6 cases of GCH\u2010AHA and 6 cases of autoimmune hepatitis (AIH) with early childhood onset (3 type 1 and 3 type 2). Liver biopsies were graded for portal and periportal inflammation and for giant cells. Immunohistochemistry characterized cellular inflammation and complement involvement in injury by showing C5b\u20109 complex in hepatocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>Clinical and biochemical features at presentation were generally similar; however, the absence of autoantibodies and the presence of Coombs positivity did distinguish GCH\u2010AHA from early\u2010onset AIH. Liver biopsy pathology in CGH\u2010AHA showed giant cells and little inflammation, whereas AIH showed the opposite. C5b\u20109 staining showed high\u2010grade complement\u2010mediated pan\u2010lobular hepatocyte injury in all of the cases with GCH\u2010AHA, whereas little C5b\u20109 was seen in hepatocytes in cases with AIH. Inflammation in GCH\u2010AHA comprised mainly lobular macrophages and neutrophils, whereas portal and periportal T\u2010cell and B\u2010cell inflammation characterized cases with AIH. Most cases with AIH responded to therapy with prednisone and azathioprine, whereas most cases with GCH\u2010AHA responded only to rituximab.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p>Widespread complement\u2010mediated hepatocyte injury and typical C3a and C5a complement\u2010driven liver inflammation along with Coombs\u2010positive hemolytic anemia in GCH\u2010AHA provide convincing evidence that systemic B\u2010cell autoimmunity plays a central pathologic mechanism in the disease. Our findings support B\u2010cell\u2013directed immunotherapy as a first\u2010line treatment of GCH\u2010AHA.<\/jats:p><\/jats:sec>","DOI":"10.1097\/mpg.0b013e3182a98dbe","type":"journal-article","created":{"date-parts":[[2013,8,22]],"date-time":"2013-08-22T14:49:08Z","timestamp":1377182948000},"page":"74-80","source":"Crossref","is-referenced-by-count":25,"title":["Humoral Immune Mechanism of Liver Injury in Giant Cell Hepatitis With Autoimmune Hemolytic Anemia"],"prefix":"10.1002","volume":"58","author":[{"given":"Peter F.","family":"Whitington","sequence":"first","affiliation":[{"name":"Ann and Robert H. Lurie Children's Hospital of Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam B.","family":"Vos","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Emory University Atlanta GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee M.","family":"Bass","sequence":"additional","affiliation":[{"name":"Ann and Robert H. Lurie Children's Hospital of Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector","family":"Melin\u2010Aldana","sequence":"additional","affiliation":[{"name":"Ann and Robert H. 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