*Ann and Robert H. Lurie Children's Hospital of Chicago, IL †Department of Pediatrics, Emory University, Atlanta, GA ‡Department of Pediatrics, CHU Sainte Justine, University of Montreal, Montreal, Quebec, Canada.
J Pediatr Gastroenterol Nutr. 2014 Jan;58(1):74-80. doi: 10.1097/MPG.0b013e3182a98dbe.
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.
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.
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.
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.
伴有自身免疫性溶血性贫血的巨细胞肝炎（GCH-AHA）被认为是一种自身免疫性疾病，但肝损伤的机制尚不清楚。我们提出，在 GCH-AHA 中，体液免疫是驱动进行性肝损伤的主要力量。
我们研究了 6 例 GCH-AHA 和 6 例早发性自身免疫性肝炎（AIH）病例（3 例 1 型和 3 例 2 型）。通过显示肝细胞中 C5b-9 复合物，对肝活检进行门脉和门周炎症以及巨细胞分级。免疫组织化学通过显示肝细胞中 C5b-9 复合物，来鉴定细胞炎症和补体在损伤中的参与。
在发病时，临床和生化特征通常相似；然而，缺乏自身抗体和存在抗球蛋白阳性确实将 GCH-AHA 与早发性 AIH 区分开来。CGH-AHA 的肝活检病理学显示巨细胞和炎症较少，而 AIH 则相反。所有 GCH-AHA 病例均显示高水平补体介导的全小叶肝细胞损伤，而 AIH 病例中很少见肝细胞 C5b-9 染色。GCH-AHA 的炎症主要由小叶巨噬细胞和中性粒细胞组成，而 AIH 的门脉和门周 T 细胞和 B 细胞炎症则构成了该疾病的特征。大多数 AIH 病例对泼尼松和硫唑嘌呤治疗有反应，而大多数 GCH-AHA 病例仅对利妥昔单抗有反应。
广泛的补体介导的肝细胞损伤以及典型的 C3a 和 C5a 补体驱动的肝脏炎症以及 GCH-AHA 中的 Coombs 阳性溶血性贫血，为系统性 B 细胞自身免疫在疾病中发挥中心病理机制提供了令人信服的证据。我们的发现支持 B 细胞靶向免疫疗法作为 GCH-AHA 的一线治疗。
