Skip Navigation LinksHome > January 2014 - Volume 58 - Issue 1 > Humoral Immune Mechanism of Liver Injury in Giant Cell Hepat...
Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/MPG.0b013e3182a98dbe
Original Articles: Hepatology and Nutrition

Humoral Immune Mechanism of Liver Injury in Giant Cell Hepatitis With Autoimmune Hemolytic Anemia

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

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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.

© 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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