Humoral immune mechanism of liver injury in giant cell hepatitis with autoimmune hemolytic anemia

Peter F Whitington, Miriam B. Vos*, Lee M Bass, Hector Melin-Aldana, Rene Romero, Claude C. Roy, Fernando Alvarez

*Corresponding author for this work

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Background and Aims: Giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA) is presumed to be an autoimmune disease, but the mechanism of liver injury is unknown. We proposed that in CGH-AHA, the humoral limb of autoimmunity is the dominant force driving progressive liver injury. METHODS: We studied 6 cases of GCH-AHA 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-9 complex in hepatocytes. RESULTS: Clinical and biochemical features at presentation were generally similar; however, the absence of autoantibodies and the presence of Coombs positivity did distinguish GCH-AHA from early-onset AIH. Liver biopsy pathology in CGH-AHA showed giant cells and little inflammation, whereas AIH showed the opposite. C5b-9 staining showed high-grade complement-mediated pan-lobular hepatocyte injury in all of the cases with GCH-AHA, whereas little C5b-9 was seen in hepatocytes in cases with AIH. Inflammation in GCH-AHA comprised mainly lobular macrophages and neutrophils, whereas portal and periportal T-cell and B-cell inflammation characterized cases with AIH. Most cases with AIH responded to therapy with prednisone and azathioprine, whereas most cases with GCH-AHA responded only to rituximab. CONCLUSIONS: Widespread complement-mediated hepatocyte injury and typical C3a and C5a complement-driven liver inflammation along with Coombs-positive hemolytic anemia in GCH-AHA provide convincing evidence that systemic B-cell autoimmunity plays a central pathologic mechanism in the disease. Our findings support B-cell-directed immunotherapy as a first-line treatment of GCH-AHA.

Original languageEnglish (US)
Pages (from-to)74-80
Number of pages7
JournalJournal of pediatric gastroenterology and nutrition
Volume58
Issue number1
DOIs
StatePublished - Jan 1 2014

Keywords

  • complement
  • giant cell
  • hemolytic anemia
  • hepatocyte
  • humoral immunity

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Gastroenterology

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